Neurology

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Click to view more from Federal Health Care Data Trends 2025.

Click to view more from Federal Health Care Data Trends 2025.

Click to view more from Federal Health Care Data Trends 2025.

Chronic cough remains a common reason for consultation in pulmonology post–COVID-19. But what do we really know about this condition, now 5 years after the pandemic’s onset? This topic was discussed at the recent French-Speaking Pneumology Congress held in Marseille, France, from January 24-26, 2025.

Before discussing post-COVID cough, it is crucial to differentiate between an acute cough, often viral in origin (including those associated with SARS-CoV-2), a subacute cough (lasting 3-8 weeks), and a chronic cough (persisting over 8 weeks).

“This distinction allows us to tailor treatment and prescribe the appropriate investigations, according to the duration and the probability of symptom resolution,” explained Laurent Guilleminault, MD, PhD, pulmonologist at Toulouse University Hospital Centre, Toulouse, France.

In the case of an acute cough, for instance, after a viral infection, the probability of spontaneous resolution is very high. It is often unnecessary to carry out additional examinations or initiate specific treatments because none has proven its effectiveness in shortening this type of cough. On the other hand, when a cough persists beyond 8 weeks, the chance of spontaneous resolution decreases considerably. “This is when an assessment is necessary to identify a possible underlying cause,” Guilleminault noted.

“The absence of coughing during the consultation should not lead to ruling out a diagnosis,” he added.

Neurological Link

A large-scale French study of 70,000 patients examined the demographic profiles of patients with COVID-19. It revealed a lower frequency of coughing among children and older individuals, with a notable prevalence among adults aged 30-60 years.

Furthermore, during the acute phase of COVID, coughing did not appear to indicate severity. A comparison between survivors and nonsurvivors revealed no significant differences in the frequency and severity of coughing. Another study concluded that, contrary to expectations, COVID-related pneumonia, although potentially severe, does not necessarily involve severe cough.

These findings highlight the absence of a direct link between coughing and pulmonary involvement in patients with COVID-19.

“Coughing appears to be more closely linked to neurological dysfunction than to classic respiratory involvement. A distinction that is essential for better understanding the pathophysiology of the disease and guiding therapeutic strategies,” Guilleminault noted.

Cough Mechanism

“The analysis of cough in the context of phylogenetic evolution is fascinating,” explained Guilleminault. “It illustrates how this reflex has provided an advantage to the virus for its propagation.” Studies on the transmission of SARS-CoV-2 have confirmed that coughing plays a key role in the spread of viral particles. However, this mechanism does not involve severe pulmonary damage. The primary goal of the virus is to induce neurological dysfunction in the host by triggering a cough reflex. This neurological activation enables the virus to trigger a cough reflex for dissemination even without significant pulmonary damage. This mechanism provides an evolutionary advantage by enhancing the ability of the virus to spread and colonize new hosts.

The cough mechanism remains partially understood and involves cough hypersensitivity, characterized by increased neural responsivity to a range of stimuli that affect the airways, lungs, and other tissues innervated by common nerve supplies. The cough reflex begins with the activation of sensitive peripheral receptors located mainly in the respiratory tract that detect irritants or abnormalities.

These receptors, such as P2X2, P2X3, and others, transmit information to the brainstem, which coordinates the reflex response. This process is modulated by cortical controls that normally inhibit spontaneous coughing, explaining why we do not cough constantly even in the presence of moderate stimuli.

However, when there is an imbalance in this inhibition mechanism, coughing can be triggered either excessively or uncontrollably. SARS-CoV-2 appears to interact directly with these peripheral receptors, stimulating the cough reflex. The widespread presence and density of these receptors make this mechanism highly effective for the virus’s transmission.

Additionally, the vagus nerve likely plays a central role in triggering cough, particularly in viral infections. Studies of influenza have shown the involvement of sensory cells associated with the vagus nerve.

The virus stimulates the vagus nerve, which activates the cough reflex. Research suggests that neurotropism, neuroinflammation, and neuroimmunomodulation via the vagal sensory nerves, which are involved in SARS-CoV-2 infection, lead to cough hypersensitivity.

One question remains: Could vagus nerve involvement prolong coughing beyond the active phase of viral infection? The data indicate that viral infection significantly increases the sensitivity of the cough reflex, regardless of the level of irritation. The brain areas involved in inhibiting this reflex appear less effective during viral infection, resulting in reduced inhibitory control and easier triggering of cough. This phenomenon reflects temporary dysfunction of the neurological modulation system, which gradually recovers after recovery.

Long-Term Effects

The epidemiology of post-COVID cough and its integration into the framework of the long COVID framework remain subjects of ongoing debate. Early studies have revealed that cough could be either an isolated symptom or associated with other manifestations of long COVID. These studies were often conducted over relatively short periods (14-110 days) and estimated that approximately 19% of patients with long COVID experienced persistent cough. Another study found that 14% of patients reported cough between 3 weeks and 3 months after hospital discharge for COVID-19.

Longer follow-up periods showed a significant decrease in the prevalence of cough over time. For instance, a 1-year study reported that only 2.5% of patients had episodes of chronic cough.

However, a 2023 study published in JAMA found that the prevalence of post-COVID chronic cough exceeded 30% in some groups of patients.

“It is not relevant to wait so long before acting,” Guilleminault said. A reasonable threshold for evaluation and treatment is 8-12 weeks postinfection to begin investigations and consider appropriate treatment. What should be done when a patient presents with “Doctor, I had COVID, I have a cough, and it hasn’t stopped?” These situations are common in clinical practice. In terms of severity, quality of life, and overall impact, patients with chronic post-COVID cough are not significantly different from those with other chronic coughs. Moreover, both conditions involve a real neurological dysfunction.

Same Diagnostic Steps

Management should follow existing guidelines, including the recent French recommendations for chronic cough.

A visual analog scale can be used, and possible complications should be assessed. A chest x-ray is recommended to identify any warning signs, such as cough, although linked to COVID — may coincide with other conditions, such as bronchial cancer. In smokers, chest CT should be considered to rule out neoplastic pathology. The presence of interstitial lesions, particularly fibrosing lesions, suggests that fibrosing interstitial pneumonia requires specialized management.

Smoking, which is an aggravating factor, should be discontinued. Discontinuing angiotensin-converting enzyme inhibitors for 4 weeks can help determine if they contribute to cough.

The three most common causes of chronic cough — rhinosinusitis, asthma, and gastroesophageal reflux disease — should be ruled out. Diagnosis is based on history, physical examination, and specific tests: Nasofibroscopy for rhinosinusitis, spirometry, fractional exhaled nitric oxide for asthma and clinical history of gastroesophageal reflux disease. Studies have indicated that asthma may develop after a COVID infection.

Laryngeal abnormalities are also common in chronic post-COVID cough. One study found that a quarter of patients had increased laryngeal sensitivity or voice changes. “The larynx, a highly cough-producing organ, causes more coughing than the lungs,” Guilleminault explained.

Laryngeal abnormalities are frequently observed. A study found that 63% of patients experienced dysphonia, 56% had a sensation of a foreign body in the larynx, and 10% experienced laryngospasms.

These issues are common in patients with post-COVID cough and are often associated with neurological dysfunction. Innervation of the larynx is complex and can be affected by viruses, leading to hypersensitivity, paresthesia, and other sensory disturbances, which may explain the laryngeal symptoms observed in these patients.

Next Steps

If common causes such as asthma, abnormal imaging findings, or laryngeal pathology are ruled out, the condition may be classified as a chronic refractory or unexplained cough. In these cases, the neurological origin is likely due to nervous system dysfunction. Neuromodulatory treatments including amitriptyline, pregabalin, and gabapentin may be considered in some cases. Corticosteroids are generally ineffective against chronic coughs.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Chronic cough remains a common reason for consultation in pulmonology post–COVID-19. But what do we really know about this condition, now 5 years after the pandemic’s onset? This topic was discussed at the recent French-Speaking Pneumology Congress held in Marseille, France, from January 24-26, 2025.

Before discussing post-COVID cough, it is crucial to differentiate between an acute cough, often viral in origin (including those associated with SARS-CoV-2), a subacute cough (lasting 3-8 weeks), and a chronic cough (persisting over 8 weeks).

“This distinction allows us to tailor treatment and prescribe the appropriate investigations, according to the duration and the probability of symptom resolution,” explained Laurent Guilleminault, MD, PhD, pulmonologist at Toulouse University Hospital Centre, Toulouse, France.

In the case of an acute cough, for instance, after a viral infection, the probability of spontaneous resolution is very high. It is often unnecessary to carry out additional examinations or initiate specific treatments because none has proven its effectiveness in shortening this type of cough. On the other hand, when a cough persists beyond 8 weeks, the chance of spontaneous resolution decreases considerably. “This is when an assessment is necessary to identify a possible underlying cause,” Guilleminault noted.

“The absence of coughing during the consultation should not lead to ruling out a diagnosis,” he added.

Neurological Link

A large-scale French study of 70,000 patients examined the demographic profiles of patients with COVID-19. It revealed a lower frequency of coughing among children and older individuals, with a notable prevalence among adults aged 30-60 years.

Furthermore, during the acute phase of COVID, coughing did not appear to indicate severity. A comparison between survivors and nonsurvivors revealed no significant differences in the frequency and severity of coughing. Another study concluded that, contrary to expectations, COVID-related pneumonia, although potentially severe, does not necessarily involve severe cough.

These findings highlight the absence of a direct link between coughing and pulmonary involvement in patients with COVID-19.

“Coughing appears to be more closely linked to neurological dysfunction than to classic respiratory involvement. A distinction that is essential for better understanding the pathophysiology of the disease and guiding therapeutic strategies,” Guilleminault noted.

Cough Mechanism

“The analysis of cough in the context of phylogenetic evolution is fascinating,” explained Guilleminault. “It illustrates how this reflex has provided an advantage to the virus for its propagation.” Studies on the transmission of SARS-CoV-2 have confirmed that coughing plays a key role in the spread of viral particles. However, this mechanism does not involve severe pulmonary damage. The primary goal of the virus is to induce neurological dysfunction in the host by triggering a cough reflex. This neurological activation enables the virus to trigger a cough reflex for dissemination even without significant pulmonary damage. This mechanism provides an evolutionary advantage by enhancing the ability of the virus to spread and colonize new hosts.

The cough mechanism remains partially understood and involves cough hypersensitivity, characterized by increased neural responsivity to a range of stimuli that affect the airways, lungs, and other tissues innervated by common nerve supplies. The cough reflex begins with the activation of sensitive peripheral receptors located mainly in the respiratory tract that detect irritants or abnormalities.

These receptors, such as P2X2, P2X3, and others, transmit information to the brainstem, which coordinates the reflex response. This process is modulated by cortical controls that normally inhibit spontaneous coughing, explaining why we do not cough constantly even in the presence of moderate stimuli.

However, when there is an imbalance in this inhibition mechanism, coughing can be triggered either excessively or uncontrollably. SARS-CoV-2 appears to interact directly with these peripheral receptors, stimulating the cough reflex. The widespread presence and density of these receptors make this mechanism highly effective for the virus’s transmission.

Additionally, the vagus nerve likely plays a central role in triggering cough, particularly in viral infections. Studies of influenza have shown the involvement of sensory cells associated with the vagus nerve.

The virus stimulates the vagus nerve, which activates the cough reflex. Research suggests that neurotropism, neuroinflammation, and neuroimmunomodulation via the vagal sensory nerves, which are involved in SARS-CoV-2 infection, lead to cough hypersensitivity.

One question remains: Could vagus nerve involvement prolong coughing beyond the active phase of viral infection? The data indicate that viral infection significantly increases the sensitivity of the cough reflex, regardless of the level of irritation. The brain areas involved in inhibiting this reflex appear less effective during viral infection, resulting in reduced inhibitory control and easier triggering of cough. This phenomenon reflects temporary dysfunction of the neurological modulation system, which gradually recovers after recovery.

Long-Term Effects

The epidemiology of post-COVID cough and its integration into the framework of the long COVID framework remain subjects of ongoing debate. Early studies have revealed that cough could be either an isolated symptom or associated with other manifestations of long COVID. These studies were often conducted over relatively short periods (14-110 days) and estimated that approximately 19% of patients with long COVID experienced persistent cough. Another study found that 14% of patients reported cough between 3 weeks and 3 months after hospital discharge for COVID-19.

Longer follow-up periods showed a significant decrease in the prevalence of cough over time. For instance, a 1-year study reported that only 2.5% of patients had episodes of chronic cough.

However, a 2023 study published in JAMA found that the prevalence of post-COVID chronic cough exceeded 30% in some groups of patients.

“It is not relevant to wait so long before acting,” Guilleminault said. A reasonable threshold for evaluation and treatment is 8-12 weeks postinfection to begin investigations and consider appropriate treatment. What should be done when a patient presents with “Doctor, I had COVID, I have a cough, and it hasn’t stopped?” These situations are common in clinical practice. In terms of severity, quality of life, and overall impact, patients with chronic post-COVID cough are not significantly different from those with other chronic coughs. Moreover, both conditions involve a real neurological dysfunction.

Same Diagnostic Steps

Management should follow existing guidelines, including the recent French recommendations for chronic cough.

A visual analog scale can be used, and possible complications should be assessed. A chest x-ray is recommended to identify any warning signs, such as cough, although linked to COVID — may coincide with other conditions, such as bronchial cancer. In smokers, chest CT should be considered to rule out neoplastic pathology. The presence of interstitial lesions, particularly fibrosing lesions, suggests that fibrosing interstitial pneumonia requires specialized management.

Smoking, which is an aggravating factor, should be discontinued. Discontinuing angiotensin-converting enzyme inhibitors for 4 weeks can help determine if they contribute to cough.

The three most common causes of chronic cough — rhinosinusitis, asthma, and gastroesophageal reflux disease — should be ruled out. Diagnosis is based on history, physical examination, and specific tests: Nasofibroscopy for rhinosinusitis, spirometry, fractional exhaled nitric oxide for asthma and clinical history of gastroesophageal reflux disease. Studies have indicated that asthma may develop after a COVID infection.

Laryngeal abnormalities are also common in chronic post-COVID cough. One study found that a quarter of patients had increased laryngeal sensitivity or voice changes. “The larynx, a highly cough-producing organ, causes more coughing than the lungs,” Guilleminault explained.

Laryngeal abnormalities are frequently observed. A study found that 63% of patients experienced dysphonia, 56% had a sensation of a foreign body in the larynx, and 10% experienced laryngospasms.

These issues are common in patients with post-COVID cough and are often associated with neurological dysfunction. Innervation of the larynx is complex and can be affected by viruses, leading to hypersensitivity, paresthesia, and other sensory disturbances, which may explain the laryngeal symptoms observed in these patients.

Next Steps

If common causes such as asthma, abnormal imaging findings, or laryngeal pathology are ruled out, the condition may be classified as a chronic refractory or unexplained cough. In these cases, the neurological origin is likely due to nervous system dysfunction. Neuromodulatory treatments including amitriptyline, pregabalin, and gabapentin may be considered in some cases. Corticosteroids are generally ineffective against chronic coughs.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Chronic cough remains a common reason for consultation in pulmonology post–COVID-19. But what do we really know about this condition, now 5 years after the pandemic’s onset? This topic was discussed at the recent French-Speaking Pneumology Congress held in Marseille, France, from January 24-26, 2025.

Before discussing post-COVID cough, it is crucial to differentiate between an acute cough, often viral in origin (including those associated with SARS-CoV-2), a subacute cough (lasting 3-8 weeks), and a chronic cough (persisting over 8 weeks).

“This distinction allows us to tailor treatment and prescribe the appropriate investigations, according to the duration and the probability of symptom resolution,” explained Laurent Guilleminault, MD, PhD, pulmonologist at Toulouse University Hospital Centre, Toulouse, France.

In the case of an acute cough, for instance, after a viral infection, the probability of spontaneous resolution is very high. It is often unnecessary to carry out additional examinations or initiate specific treatments because none has proven its effectiveness in shortening this type of cough. On the other hand, when a cough persists beyond 8 weeks, the chance of spontaneous resolution decreases considerably. “This is when an assessment is necessary to identify a possible underlying cause,” Guilleminault noted.

“The absence of coughing during the consultation should not lead to ruling out a diagnosis,” he added.

Neurological Link

A large-scale French study of 70,000 patients examined the demographic profiles of patients with COVID-19. It revealed a lower frequency of coughing among children and older individuals, with a notable prevalence among adults aged 30-60 years.

Furthermore, during the acute phase of COVID, coughing did not appear to indicate severity. A comparison between survivors and nonsurvivors revealed no significant differences in the frequency and severity of coughing. Another study concluded that, contrary to expectations, COVID-related pneumonia, although potentially severe, does not necessarily involve severe cough.

These findings highlight the absence of a direct link between coughing and pulmonary involvement in patients with COVID-19.

“Coughing appears to be more closely linked to neurological dysfunction than to classic respiratory involvement. A distinction that is essential for better understanding the pathophysiology of the disease and guiding therapeutic strategies,” Guilleminault noted.

Cough Mechanism

“The analysis of cough in the context of phylogenetic evolution is fascinating,” explained Guilleminault. “It illustrates how this reflex has provided an advantage to the virus for its propagation.” Studies on the transmission of SARS-CoV-2 have confirmed that coughing plays a key role in the spread of viral particles. However, this mechanism does not involve severe pulmonary damage. The primary goal of the virus is to induce neurological dysfunction in the host by triggering a cough reflex. This neurological activation enables the virus to trigger a cough reflex for dissemination even without significant pulmonary damage. This mechanism provides an evolutionary advantage by enhancing the ability of the virus to spread and colonize new hosts.

The cough mechanism remains partially understood and involves cough hypersensitivity, characterized by increased neural responsivity to a range of stimuli that affect the airways, lungs, and other tissues innervated by common nerve supplies. The cough reflex begins with the activation of sensitive peripheral receptors located mainly in the respiratory tract that detect irritants or abnormalities.

These receptors, such as P2X2, P2X3, and others, transmit information to the brainstem, which coordinates the reflex response. This process is modulated by cortical controls that normally inhibit spontaneous coughing, explaining why we do not cough constantly even in the presence of moderate stimuli.

However, when there is an imbalance in this inhibition mechanism, coughing can be triggered either excessively or uncontrollably. SARS-CoV-2 appears to interact directly with these peripheral receptors, stimulating the cough reflex. The widespread presence and density of these receptors make this mechanism highly effective for the virus’s transmission.

Additionally, the vagus nerve likely plays a central role in triggering cough, particularly in viral infections. Studies of influenza have shown the involvement of sensory cells associated with the vagus nerve.

The virus stimulates the vagus nerve, which activates the cough reflex. Research suggests that neurotropism, neuroinflammation, and neuroimmunomodulation via the vagal sensory nerves, which are involved in SARS-CoV-2 infection, lead to cough hypersensitivity.

One question remains: Could vagus nerve involvement prolong coughing beyond the active phase of viral infection? The data indicate that viral infection significantly increases the sensitivity of the cough reflex, regardless of the level of irritation. The brain areas involved in inhibiting this reflex appear less effective during viral infection, resulting in reduced inhibitory control and easier triggering of cough. This phenomenon reflects temporary dysfunction of the neurological modulation system, which gradually recovers after recovery.

Long-Term Effects

The epidemiology of post-COVID cough and its integration into the framework of the long COVID framework remain subjects of ongoing debate. Early studies have revealed that cough could be either an isolated symptom or associated with other manifestations of long COVID. These studies were often conducted over relatively short periods (14-110 days) and estimated that approximately 19% of patients with long COVID experienced persistent cough. Another study found that 14% of patients reported cough between 3 weeks and 3 months after hospital discharge for COVID-19.

Longer follow-up periods showed a significant decrease in the prevalence of cough over time. For instance, a 1-year study reported that only 2.5% of patients had episodes of chronic cough.

However, a 2023 study published in JAMA found that the prevalence of post-COVID chronic cough exceeded 30% in some groups of patients.

“It is not relevant to wait so long before acting,” Guilleminault said. A reasonable threshold for evaluation and treatment is 8-12 weeks postinfection to begin investigations and consider appropriate treatment. What should be done when a patient presents with “Doctor, I had COVID, I have a cough, and it hasn’t stopped?” These situations are common in clinical practice. In terms of severity, quality of life, and overall impact, patients with chronic post-COVID cough are not significantly different from those with other chronic coughs. Moreover, both conditions involve a real neurological dysfunction.

Same Diagnostic Steps

Management should follow existing guidelines, including the recent French recommendations for chronic cough.

A visual analog scale can be used, and possible complications should be assessed. A chest x-ray is recommended to identify any warning signs, such as cough, although linked to COVID — may coincide with other conditions, such as bronchial cancer. In smokers, chest CT should be considered to rule out neoplastic pathology. The presence of interstitial lesions, particularly fibrosing lesions, suggests that fibrosing interstitial pneumonia requires specialized management.

Smoking, which is an aggravating factor, should be discontinued. Discontinuing angiotensin-converting enzyme inhibitors for 4 weeks can help determine if they contribute to cough.

The three most common causes of chronic cough — rhinosinusitis, asthma, and gastroesophageal reflux disease — should be ruled out. Diagnosis is based on history, physical examination, and specific tests: Nasofibroscopy for rhinosinusitis, spirometry, fractional exhaled nitric oxide for asthma and clinical history of gastroesophageal reflux disease. Studies have indicated that asthma may develop after a COVID infection.

Laryngeal abnormalities are also common in chronic post-COVID cough. One study found that a quarter of patients had increased laryngeal sensitivity or voice changes. “The larynx, a highly cough-producing organ, causes more coughing than the lungs,” Guilleminault explained.

Laryngeal abnormalities are frequently observed. A study found that 63% of patients experienced dysphonia, 56% had a sensation of a foreign body in the larynx, and 10% experienced laryngospasms.

These issues are common in patients with post-COVID cough and are often associated with neurological dysfunction. Innervation of the larynx is complex and can be affected by viruses, leading to hypersensitivity, paresthesia, and other sensory disturbances, which may explain the laryngeal symptoms observed in these patients.

Next Steps

If common causes such as asthma, abnormal imaging findings, or laryngeal pathology are ruled out, the condition may be classified as a chronic refractory or unexplained cough. In these cases, the neurological origin is likely due to nervous system dysfunction. Neuromodulatory treatments including amitriptyline, pregabalin, and gabapentin may be considered in some cases. Corticosteroids are generally ineffective against chronic coughs.

This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

New evidence–based clinical practice guidelines from the Alzheimer’s Association provide updated recommendations on evaluating individuals suspected of having Alzheimer’s disease and Alzheimer’s disease–related neurodegenerative disorders in both primary and specialty care settings.

This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.

 

What’s New? 

“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.

“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.

Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.

Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.

 

What Are the Key Recommendations?

The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations: 

Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.

Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.

Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.

History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.

Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.

Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.

Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.

Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.

Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.

Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.

Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.

Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.

Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.

Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.

Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.

Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.

 

Future Directions?

Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.

“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.

Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.” 

However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.

 

New Appropriate Use Guidance

A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.

They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.

“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.

The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.

Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.

“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.

“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.

The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.

In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”

This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.

A version of this article first appeared on Medscape.com.

New evidence–based clinical practice guidelines from the Alzheimer’s Association provide updated recommendations on evaluating individuals suspected of having Alzheimer’s disease and Alzheimer’s disease–related neurodegenerative disorders in both primary and specialty care settings.

This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.

 

What’s New? 

“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.

“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.

Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.

Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.

 

What Are the Key Recommendations?

The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations: 

Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.

Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.

Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.

History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.

Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.

Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.

Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.

Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.

Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.

Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.

Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.

Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.

Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.

Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.

Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.

Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.

 

Future Directions?

Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.

“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.

Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.” 

However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.

 

New Appropriate Use Guidance

A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.

They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.

“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.

The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.

Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.

“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.

“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.

The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.

In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”

This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.

A version of this article first appeared on Medscape.com.

New evidence–based clinical practice guidelines from the Alzheimer’s Association provide updated recommendations on evaluating individuals suspected of having Alzheimer’s disease and Alzheimer’s disease–related neurodegenerative disorders in both primary and specialty care settings.

This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.

 

What’s New? 

“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.

“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.

Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.

Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.

 

What Are the Key Recommendations?

The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations: 

Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.

Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.

Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.

History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.

Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.

Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.

Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.

Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.

Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.

Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.

Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.

Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.

Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.

Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.

Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.

Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.

 

Future Directions?

Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.

“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.

Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.” 

However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.

 

New Appropriate Use Guidance

A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.

They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.

“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.

The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.

Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.

“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.

“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.

The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.

In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”

This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.

A version of this article first appeared on Medscape.com.

You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.

The Brain Benefits of BP Lowering

It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.

In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.

Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.

 

Potential Harms of Lowering BP

All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions. 

When it comes to dementia, there is also a concern that overtreating high BP could make things worse. Hypotension and decreased cerebral perfusion could hasten cognitive decline by depriving the brain of that all too necessary oxygen. 

A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.

A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.

 

Deprescribing, Yes or No? 

However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.

Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress. 

Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.

The Brain Benefits of BP Lowering

It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.

In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.

Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.

 

Potential Harms of Lowering BP

All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions. 

When it comes to dementia, there is also a concern that overtreating high BP could make things worse. Hypotension and decreased cerebral perfusion could hasten cognitive decline by depriving the brain of that all too necessary oxygen. 

A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.

A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.

 

Deprescribing, Yes or No? 

However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.

Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress. 

Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.

The Brain Benefits of BP Lowering

It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.

In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.

Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.

 

Potential Harms of Lowering BP

All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions. 

When it comes to dementia, there is also a concern that overtreating high BP could make things worse. Hypotension and decreased cerebral perfusion could hasten cognitive decline by depriving the brain of that all too necessary oxygen. 

A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.

A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.

 

Deprescribing, Yes or No? 

However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.

Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress. 

Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

• Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
• They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
• An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
• A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

• More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
• Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
• Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
• Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

• Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
• They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
• An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
• A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

• More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
• Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
• Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
• Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

• Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
• They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
• An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
• A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

• More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
• Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
• Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
• Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Children with asthma scored significantly lower than those without asthma on measures of episodic memory, based on longitudinal data from nearly 500 individuals.

Animal models have shown associations between asthma and memory problems, but data for children are lacking, wrote Nicholas J. Christopher-Hayes, MA, of the University of California, Davis, and colleagues.

“Asthma is very frequent among children, and there is mounting evidence from rodent models that asthma may result in neural injury in the hippocampus, which in turn may cause memory loss,” Christopher-Hayes said in an interview. “Although there is also a good amount of research with older adults, very little research has been done with children, the period that is most frequently linked to asthma onset,” he said. Therefore, the researchers leveraged a large national study on child development to examine development of memory as a function of asthma exposure.

In this study published in JAMA Network Open, the researchers conducted both a longitudinal and cross-sectional analysis of data from the Adolescent Brain Cognitive Development Study, which began in 2015. Children were enrolled at ages 9-10 years with a follow-up assessment 1-2 years later.

The participants were categorized as early childhood-onset asthma (asthma at baseline and follow-up), later childhood-onset asthma (asthma at follow-up only), or no asthma history. The primary outcome of the longitudinal analysis was episodic memory. Approximately half of the participants were boys, and slightly more than half were White.

Among 474 children reviewed in the longitudinal analysis, 135 had early-onset asthma, 102 had later-onset asthma, and 237 had no asthma and served as control individuals. Overall, those with early-onset asthma showed significantly lower rates of longitudinal memory improvements at follow-up compared with the comparison group (P < .01).

Developmental memory improvement in children with later-onset asthma was not significantly different from the control individuals. 

Secondary outcomes included processing speed and inhibition, and attention. In a cross-sectional analysis with a larger sample of 2062 children from the same database (1031 with any asthma), those with asthma scored significantly lower on measures not only of episodic memory but also processing speed and inhibition/attention than children with no asthma, with P values of .04, .01, and .02, respectively.

The results were limited by several factors, including the reliance on parent reports for indicators of asthma and the lack of data on the potential effect of prescription corticosteroid use on neurocognitive development, the researchers noted.

The mechanism behind the association remains unclear; the inflammation associated with asthma may disrupt neural processing and manifest as cognitive dysfunction, as has been seen in rodent models of asthma, the researchers wrote. “It is possible that associations between asthma and developmental trajectories emerge earlier for memory, perhaps due to its sensitivity to subtle hippocampal injury,” they noted.

Longer follow-up studies are needed to fully understand how childhood asthma predicts memory declines or difficulties in childhood and beyond, said Christopher-Hayes. “We also need additional studies to understand why children who were diagnosed earlier and had asthma for longer seem to be particularly affected,” he said.

The results of this study were consistent with previous findings and therefore not surprising, senior author Simona Ghetti, PhD, a professor of psychology at the University of California, Davis, said in an interview. However, the finding that the extent of exposure to asthma was associated with slower memory improvement in childhood was striking, she said. That children with an earlier asthma onset who had disease indicators for a longer period showed a slower development of memory over time, suggests that asthma exposure may affect the developmental trajectory of memory, Ghetti noted. 

“Recommendations to clinicians are premature because we need a better understanding of the boundary conditions, such as the minimal level of asthma exposure that might generate memory difficulties,” said Ghetti.

“Nevertheless, our results underscore the importance of looking at asthma as a potential source of cognitive difficulty in children,” she said.

 

Asthma’s Extensive Effect

Evidence is mounting that a diagnosis of asthma may have implications outside the pulmonary system, Diego J. Maselli, MD, professor and chief of the Division of Pulmonary Diseases & Critical Care at UT Health, San Antonio, said in an interview. 

“Asthmatics may be at risk of nasal polyps, allergic rhinitis, and other allergic conditions, but there is emerging of evidence inflammation associated with asthma may affect other organ systems,” said Maselli, who was not involved in the study.

“For example, chronic inflammation in asthmatics may increase the risk of cardiovascular disease,” he said.

Although less is known about the effects of asthma on the nervous system, animal models suggest that inflammation associated with asthma may result in neuronal injury and potential effects on memory, said Maselli.

The findings of this study provide evidence of potential detrimental effects on the memory of children with asthma but should be interpreted with caution, Maselli said. “Children with chronic medical conditions may have an inherent disadvantage compared with their peers due to the burden of their disease, medication utilization and side effects, absenteeism from school, physical limitations, and other disease-specific circumstances,” he noted.

“Uncontrolled asthma, in particular, has strong links to low socioeconomic factors that are closely tied to access to adequate medical care, nutrition, educational institutions, and other relevant contributors to normal cognitive development,” Maselli said. Although the authors account for some of these socioeconomic factors by evaluating income and race, other variables may have influenced the results, he added.

Overall, this study’s findings suggested that the diagnosis of asthma in children may be associated with memory deficits and may influence neurodevelopment; however, more research is needed to determine whether the findings are replicated in other cohorts, said Maselli. “In particular, evaluating the effects of the severity of asthma and different asthma endotypes would be crucial to identify children with a higher risk of memory or cognitive deficits and confirm these associations,” he said.

This study was funded by the Memory and Plasticity Program at the University of California, Davis, and by a Learning, Memory, and Plasticity Training Program Fellowship grant from the National Institutes of Health. The researchers and Maselli had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com.

Children with asthma scored significantly lower than those without asthma on measures of episodic memory, based on longitudinal data from nearly 500 individuals.

Animal models have shown associations between asthma and memory problems, but data for children are lacking, wrote Nicholas J. Christopher-Hayes, MA, of the University of California, Davis, and colleagues.

“Asthma is very frequent among children, and there is mounting evidence from rodent models that asthma may result in neural injury in the hippocampus, which in turn may cause memory loss,” Christopher-Hayes said in an interview. “Although there is also a good amount of research with older adults, very little research has been done with children, the period that is most frequently linked to asthma onset,” he said. Therefore, the researchers leveraged a large national study on child development to examine development of memory as a function of asthma exposure.

In this study published in JAMA Network Open, the researchers conducted both a longitudinal and cross-sectional analysis of data from the Adolescent Brain Cognitive Development Study, which began in 2015. Children were enrolled at ages 9-10 years with a follow-up assessment 1-2 years later.

The participants were categorized as early childhood-onset asthma (asthma at baseline and follow-up), later childhood-onset asthma (asthma at follow-up only), or no asthma history. The primary outcome of the longitudinal analysis was episodic memory. Approximately half of the participants were boys, and slightly more than half were White.

Among 474 children reviewed in the longitudinal analysis, 135 had early-onset asthma, 102 had later-onset asthma, and 237 had no asthma and served as control individuals. Overall, those with early-onset asthma showed significantly lower rates of longitudinal memory improvements at follow-up compared with the comparison group (P < .01).

Developmental memory improvement in children with later-onset asthma was not significantly different from the control individuals. 

Secondary outcomes included processing speed and inhibition, and attention. In a cross-sectional analysis with a larger sample of 2062 children from the same database (1031 with any asthma), those with asthma scored significantly lower on measures not only of episodic memory but also processing speed and inhibition/attention than children with no asthma, with P values of .04, .01, and .02, respectively.

The results were limited by several factors, including the reliance on parent reports for indicators of asthma and the lack of data on the potential effect of prescription corticosteroid use on neurocognitive development, the researchers noted.

The mechanism behind the association remains unclear; the inflammation associated with asthma may disrupt neural processing and manifest as cognitive dysfunction, as has been seen in rodent models of asthma, the researchers wrote. “It is possible that associations between asthma and developmental trajectories emerge earlier for memory, perhaps due to its sensitivity to subtle hippocampal injury,” they noted.

Longer follow-up studies are needed to fully understand how childhood asthma predicts memory declines or difficulties in childhood and beyond, said Christopher-Hayes. “We also need additional studies to understand why children who were diagnosed earlier and had asthma for longer seem to be particularly affected,” he said.

The results of this study were consistent with previous findings and therefore not surprising, senior author Simona Ghetti, PhD, a professor of psychology at the University of California, Davis, said in an interview. However, the finding that the extent of exposure to asthma was associated with slower memory improvement in childhood was striking, she said. That children with an earlier asthma onset who had disease indicators for a longer period showed a slower development of memory over time, suggests that asthma exposure may affect the developmental trajectory of memory, Ghetti noted. 

“Recommendations to clinicians are premature because we need a better understanding of the boundary conditions, such as the minimal level of asthma exposure that might generate memory difficulties,” said Ghetti.

“Nevertheless, our results underscore the importance of looking at asthma as a potential source of cognitive difficulty in children,” she said.

 

Asthma’s Extensive Effect

Evidence is mounting that a diagnosis of asthma may have implications outside the pulmonary system, Diego J. Maselli, MD, professor and chief of the Division of Pulmonary Diseases & Critical Care at UT Health, San Antonio, said in an interview. 

“Asthmatics may be at risk of nasal polyps, allergic rhinitis, and other allergic conditions, but there is emerging of evidence inflammation associated with asthma may affect other organ systems,” said Maselli, who was not involved in the study.

“For example, chronic inflammation in asthmatics may increase the risk of cardiovascular disease,” he said.

Although less is known about the effects of asthma on the nervous system, animal models suggest that inflammation associated with asthma may result in neuronal injury and potential effects on memory, said Maselli.

The findings of this study provide evidence of potential detrimental effects on the memory of children with asthma but should be interpreted with caution, Maselli said. “Children with chronic medical conditions may have an inherent disadvantage compared with their peers due to the burden of their disease, medication utilization and side effects, absenteeism from school, physical limitations, and other disease-specific circumstances,” he noted.

“Uncontrolled asthma, in particular, has strong links to low socioeconomic factors that are closely tied to access to adequate medical care, nutrition, educational institutions, and other relevant contributors to normal cognitive development,” Maselli said. Although the authors account for some of these socioeconomic factors by evaluating income and race, other variables may have influenced the results, he added.

Overall, this study’s findings suggested that the diagnosis of asthma in children may be associated with memory deficits and may influence neurodevelopment; however, more research is needed to determine whether the findings are replicated in other cohorts, said Maselli. “In particular, evaluating the effects of the severity of asthma and different asthma endotypes would be crucial to identify children with a higher risk of memory or cognitive deficits and confirm these associations,” he said.

This study was funded by the Memory and Plasticity Program at the University of California, Davis, and by a Learning, Memory, and Plasticity Training Program Fellowship grant from the National Institutes of Health. The researchers and Maselli had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com.

Children with asthma scored significantly lower than those without asthma on measures of episodic memory, based on longitudinal data from nearly 500 individuals.

Animal models have shown associations between asthma and memory problems, but data for children are lacking, wrote Nicholas J. Christopher-Hayes, MA, of the University of California, Davis, and colleagues.

“Asthma is very frequent among children, and there is mounting evidence from rodent models that asthma may result in neural injury in the hippocampus, which in turn may cause memory loss,” Christopher-Hayes said in an interview. “Although there is also a good amount of research with older adults, very little research has been done with children, the period that is most frequently linked to asthma onset,” he said. Therefore, the researchers leveraged a large national study on child development to examine development of memory as a function of asthma exposure.

In this study published in JAMA Network Open, the researchers conducted both a longitudinal and cross-sectional analysis of data from the Adolescent Brain Cognitive Development Study, which began in 2015. Children were enrolled at ages 9-10 years with a follow-up assessment 1-2 years later.

The participants were categorized as early childhood-onset asthma (asthma at baseline and follow-up), later childhood-onset asthma (asthma at follow-up only), or no asthma history. The primary outcome of the longitudinal analysis was episodic memory. Approximately half of the participants were boys, and slightly more than half were White.

Among 474 children reviewed in the longitudinal analysis, 135 had early-onset asthma, 102 had later-onset asthma, and 237 had no asthma and served as control individuals. Overall, those with early-onset asthma showed significantly lower rates of longitudinal memory improvements at follow-up compared with the comparison group (P < .01).

Developmental memory improvement in children with later-onset asthma was not significantly different from the control individuals. 

Secondary outcomes included processing speed and inhibition, and attention. In a cross-sectional analysis with a larger sample of 2062 children from the same database (1031 with any asthma), those with asthma scored significantly lower on measures not only of episodic memory but also processing speed and inhibition/attention than children with no asthma, with P values of .04, .01, and .02, respectively.

The results were limited by several factors, including the reliance on parent reports for indicators of asthma and the lack of data on the potential effect of prescription corticosteroid use on neurocognitive development, the researchers noted.

The mechanism behind the association remains unclear; the inflammation associated with asthma may disrupt neural processing and manifest as cognitive dysfunction, as has been seen in rodent models of asthma, the researchers wrote. “It is possible that associations between asthma and developmental trajectories emerge earlier for memory, perhaps due to its sensitivity to subtle hippocampal injury,” they noted.

Longer follow-up studies are needed to fully understand how childhood asthma predicts memory declines or difficulties in childhood and beyond, said Christopher-Hayes. “We also need additional studies to understand why children who were diagnosed earlier and had asthma for longer seem to be particularly affected,” he said.

The results of this study were consistent with previous findings and therefore not surprising, senior author Simona Ghetti, PhD, a professor of psychology at the University of California, Davis, said in an interview. However, the finding that the extent of exposure to asthma was associated with slower memory improvement in childhood was striking, she said. That children with an earlier asthma onset who had disease indicators for a longer period showed a slower development of memory over time, suggests that asthma exposure may affect the developmental trajectory of memory, Ghetti noted. 

“Recommendations to clinicians are premature because we need a better understanding of the boundary conditions, such as the minimal level of asthma exposure that might generate memory difficulties,” said Ghetti.

“Nevertheless, our results underscore the importance of looking at asthma as a potential source of cognitive difficulty in children,” she said.

 

Asthma’s Extensive Effect

Evidence is mounting that a diagnosis of asthma may have implications outside the pulmonary system, Diego J. Maselli, MD, professor and chief of the Division of Pulmonary Diseases & Critical Care at UT Health, San Antonio, said in an interview. 

“Asthmatics may be at risk of nasal polyps, allergic rhinitis, and other allergic conditions, but there is emerging of evidence inflammation associated with asthma may affect other organ systems,” said Maselli, who was not involved in the study.

“For example, chronic inflammation in asthmatics may increase the risk of cardiovascular disease,” he said.

Although less is known about the effects of asthma on the nervous system, animal models suggest that inflammation associated with asthma may result in neuronal injury and potential effects on memory, said Maselli.

The findings of this study provide evidence of potential detrimental effects on the memory of children with asthma but should be interpreted with caution, Maselli said. “Children with chronic medical conditions may have an inherent disadvantage compared with their peers due to the burden of their disease, medication utilization and side effects, absenteeism from school, physical limitations, and other disease-specific circumstances,” he noted.

“Uncontrolled asthma, in particular, has strong links to low socioeconomic factors that are closely tied to access to adequate medical care, nutrition, educational institutions, and other relevant contributors to normal cognitive development,” Maselli said. Although the authors account for some of these socioeconomic factors by evaluating income and race, other variables may have influenced the results, he added.

Overall, this study’s findings suggested that the diagnosis of asthma in children may be associated with memory deficits and may influence neurodevelopment; however, more research is needed to determine whether the findings are replicated in other cohorts, said Maselli. “In particular, evaluating the effects of the severity of asthma and different asthma endotypes would be crucial to identify children with a higher risk of memory or cognitive deficits and confirm these associations,” he said.

This study was funded by the Memory and Plasticity Program at the University of California, Davis, and by a Learning, Memory, and Plasticity Training Program Fellowship grant from the National Institutes of Health. The researchers and Maselli had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com.

TOPLINE:

Risk for dementia is nearly 80% higher in stroke survivors than in those without stroke, a new study reveals. The data suggest risk declines within 1 year after stroke but remains elevated for up to 20 years.

METHODOLOGY:

• Researchers conducted a population-wide analysis of over 15 million people in Canada between 2002 and 2022. The study focused on adults hospitalized for ischemic stroke, intracerebral hemorrhage, or acute myocardial infarction (AMI).
• Of 175,980 stroke survivors, 99% were matched 1:1 to residents without stroke on the basis of age, sex, rural residence, neighborhood deprivation, and vascular comorbidities. In addition, 90% of patients were matched to those with AMI.
• Incident dementia diagnoses were tracked starting 90 days after stroke until death, emigration, or the end of the study, using a validated algorithm based on hospitalization for dementia, prescriptions for cholinesterase inhibitors, or physician claims within 2 years.
• The mean follow-up duration was 5.6 years.

TAKEAWAY:

• Among stroke survivors, 19% were diagnosed with dementia vs 12.5% in the reference population. The dementia rate per 100 person-years was higher among stroke survivors than in the reference population over the entire follow-up period (3.34 vs 1.89).
• Over the entire study period, dementia was 76% more likely among stroke patients (hazard ratio [HR], 1.76; 95% CI, 1.73-1.79) and 82% more likely in the AMI cohort (HR, 1.82; 95% CI, 1.79-1.85) than in the reference population.
• Time-varying analysis revealed that dementia risk was highest within the first year after stroke, with a > 2.5-fold increase at 6 months (HR, 2.51; 95% CI, 2.42-2.59), which decreased to a 1.5-fold increase at 5 years (HR, 1.51; 95% CI, 1.48-1.56) but remained elevated compared with the reference population even 20 years after the index stroke.
• Recurrent stroke was associated with an approximately threefold increased risk for dementia (single recurrent stroke adjusted HR, 2.64; 95% CI, 2.54-2.74; multiple recurrent strokes adjusted HR, 3.05; 95% CI, 2.81-3.33).

IN PRACTICE:

“While much research has been focused on reducing the risk of a second stroke, our findings make it clear that more research also is needed on developing interventions to help prevent dementia after stroke,” lead author Raed A. Joundi, MD, DPhil, McMaster University, Hamilton, Ontario, Canada, said in a press release.

“There is a need to accelerate the implementation of promising interventions or multipronged approaches into large randomized controlled trials to lower the risk of dementia,” the investigators wrote.
 

SOURCE:

The study was published online on December 4 in Neurology.

LIMITATIONS:

The study’s limitations included reliance on administrative coding without imaging data, potential underestimation of mild dementia, and lack of granular information on stroke severity, disability, and prestroke cognitive decline. While adjustments were made for healthcare contact and secondary prevention medications, residual biases may have persisted.

DISCLOSURES:

This study received funding from the Canada Brain Research Fund, Heart & Stroke Foundation of Canada, and Canadian Stroke Consortium. Two authors hold awards and positions from national organizations and academic institutions in Canada. Additional details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Risk for dementia is nearly 80% higher in stroke survivors than in those without stroke, a new study reveals. The data suggest risk declines within 1 year after stroke but remains elevated for up to 20 years.

METHODOLOGY:

• Researchers conducted a population-wide analysis of over 15 million people in Canada between 2002 and 2022. The study focused on adults hospitalized for ischemic stroke, intracerebral hemorrhage, or acute myocardial infarction (AMI).
• Of 175,980 stroke survivors, 99% were matched 1:1 to residents without stroke on the basis of age, sex, rural residence, neighborhood deprivation, and vascular comorbidities. In addition, 90% of patients were matched to those with AMI.
• Incident dementia diagnoses were tracked starting 90 days after stroke until death, emigration, or the end of the study, using a validated algorithm based on hospitalization for dementia, prescriptions for cholinesterase inhibitors, or physician claims within 2 years.
• The mean follow-up duration was 5.6 years.

TAKEAWAY:

• Among stroke survivors, 19% were diagnosed with dementia vs 12.5% in the reference population. The dementia rate per 100 person-years was higher among stroke survivors than in the reference population over the entire follow-up period (3.34 vs 1.89).
• Over the entire study period, dementia was 76% more likely among stroke patients (hazard ratio [HR], 1.76; 95% CI, 1.73-1.79) and 82% more likely in the AMI cohort (HR, 1.82; 95% CI, 1.79-1.85) than in the reference population.
• Time-varying analysis revealed that dementia risk was highest within the first year after stroke, with a > 2.5-fold increase at 6 months (HR, 2.51; 95% CI, 2.42-2.59), which decreased to a 1.5-fold increase at 5 years (HR, 1.51; 95% CI, 1.48-1.56) but remained elevated compared with the reference population even 20 years after the index stroke.
• Recurrent stroke was associated with an approximately threefold increased risk for dementia (single recurrent stroke adjusted HR, 2.64; 95% CI, 2.54-2.74; multiple recurrent strokes adjusted HR, 3.05; 95% CI, 2.81-3.33).

IN PRACTICE:

“While much research has been focused on reducing the risk of a second stroke, our findings make it clear that more research also is needed on developing interventions to help prevent dementia after stroke,” lead author Raed A. Joundi, MD, DPhil, McMaster University, Hamilton, Ontario, Canada, said in a press release.

“There is a need to accelerate the implementation of promising interventions or multipronged approaches into large randomized controlled trials to lower the risk of dementia,” the investigators wrote.
 

SOURCE:

The study was published online on December 4 in Neurology.

LIMITATIONS:

The study’s limitations included reliance on administrative coding without imaging data, potential underestimation of mild dementia, and lack of granular information on stroke severity, disability, and prestroke cognitive decline. While adjustments were made for healthcare contact and secondary prevention medications, residual biases may have persisted.

DISCLOSURES:

This study received funding from the Canada Brain Research Fund, Heart & Stroke Foundation of Canada, and Canadian Stroke Consortium. Two authors hold awards and positions from national organizations and academic institutions in Canada. Additional details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Risk for dementia is nearly 80% higher in stroke survivors than in those without stroke, a new study reveals. The data suggest risk declines within 1 year after stroke but remains elevated for up to 20 years.

METHODOLOGY:

• Researchers conducted a population-wide analysis of over 15 million people in Canada between 2002 and 2022. The study focused on adults hospitalized for ischemic stroke, intracerebral hemorrhage, or acute myocardial infarction (AMI).
• Of 175,980 stroke survivors, 99% were matched 1:1 to residents without stroke on the basis of age, sex, rural residence, neighborhood deprivation, and vascular comorbidities. In addition, 90% of patients were matched to those with AMI.
• Incident dementia diagnoses were tracked starting 90 days after stroke until death, emigration, or the end of the study, using a validated algorithm based on hospitalization for dementia, prescriptions for cholinesterase inhibitors, or physician claims within 2 years.
• The mean follow-up duration was 5.6 years.

TAKEAWAY:

• Among stroke survivors, 19% were diagnosed with dementia vs 12.5% in the reference population. The dementia rate per 100 person-years was higher among stroke survivors than in the reference population over the entire follow-up period (3.34 vs 1.89).
• Over the entire study period, dementia was 76% more likely among stroke patients (hazard ratio [HR], 1.76; 95% CI, 1.73-1.79) and 82% more likely in the AMI cohort (HR, 1.82; 95% CI, 1.79-1.85) than in the reference population.
• Time-varying analysis revealed that dementia risk was highest within the first year after stroke, with a > 2.5-fold increase at 6 months (HR, 2.51; 95% CI, 2.42-2.59), which decreased to a 1.5-fold increase at 5 years (HR, 1.51; 95% CI, 1.48-1.56) but remained elevated compared with the reference population even 20 years after the index stroke.
• Recurrent stroke was associated with an approximately threefold increased risk for dementia (single recurrent stroke adjusted HR, 2.64; 95% CI, 2.54-2.74; multiple recurrent strokes adjusted HR, 3.05; 95% CI, 2.81-3.33).

IN PRACTICE:

“While much research has been focused on reducing the risk of a second stroke, our findings make it clear that more research also is needed on developing interventions to help prevent dementia after stroke,” lead author Raed A. Joundi, MD, DPhil, McMaster University, Hamilton, Ontario, Canada, said in a press release.

“There is a need to accelerate the implementation of promising interventions or multipronged approaches into large randomized controlled trials to lower the risk of dementia,” the investigators wrote.
 

SOURCE:

The study was published online on December 4 in Neurology.

LIMITATIONS:

The study’s limitations included reliance on administrative coding without imaging data, potential underestimation of mild dementia, and lack of granular information on stroke severity, disability, and prestroke cognitive decline. While adjustments were made for healthcare contact and secondary prevention medications, residual biases may have persisted.

DISCLOSURES:

This study received funding from the Canada Brain Research Fund, Heart & Stroke Foundation of Canada, and Canadian Stroke Consortium. Two authors hold awards and positions from national organizations and academic institutions in Canada. Additional details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.