Jim Kling

A new model that predicts Barrett’s esophagus (BE) risk relies on data that can be sourced from the electronic health record.

The tool was developed and validated by researchers seeking to improve early diagnosis of esophageal adenocarcinoma (EAC) through early detection of BE. Currently, 5-year survival from EAC is just 20%, and fewer than 30% of patients have curative options at diagnosis because of late-stage disease.

Several clinical guidelines recommend screening for BE in high-risk individuals. The trouble is that adherence is low: A meta-analysis of more than 33,000 patients found that 57% of newly diagnosed EAC patients had a simultaneous, first-time diagnosis of BE, which suggests missed screening opportunities. These patients also had higher probability of late-stage disease and worse mortality outcomes than patients who had a previous BE diagnosis. Low adherence to screening guidelines can be attributed to difficulties in implementation, as well as unsatisfactory outcomes in real-world settings. In a previous study, the researchers examined the efficacy of existing guidelines in diagnosing BE in a primary care population, and found all of these screening guidelines had a low area under the receiver operating curve ranging from 0.50 to 0.60.

The researchers sought to address these challenges in the current study published in Clinical Gastroenterology and Hepatology using a model development cohort of 274 patients with BE and 1,350 patients without BE. The patients were seen at Houston Veterans Affairs clinics between 2008 and 2012, and were between ages 40 and 80 years. The researchers included common risk factors identified among existing guidelines. The final model, Houston-BEST, incorporated sex, age, race/ethnicity, smoking status, body mass index, symptoms of gastroesophageal reflux disease (heartburn or reflux at least 1 day/week), and first-degree relative history of esophageal cancer.

The validation cohorts included patients from primary care clinics at the Houston VA who were undergoing screening colonoscopy (44 with BE, 469 without BE), as well as patients at the University of Michigan, Ann Arbor, or Ann Arbor VA clinics who presented for first esophagogastroduodenoscopy (71 with BE, 916 without BE).

In the development cohort, the researchers set an a priori threshold of predicted probability that corresponded to sensitivity of 90%; the threshold predicted probability of BE was 9.3% (AUROC, 0.69; 95% confidence interval, 0.66-0.72). The specificity was 39.9% (95% CI, 37.2%-42.5%). In the Houston area validation cohort, the model had a sensitivity of 84.1% (AUROC, 0.68; 95% CI, 0.60-0.76). The number needed to treat to detect a single BE case was 11.

Among the University of Michigan/Ann Arbor validation cohort, the model had an AUROC of 0.70 (95% CI, 0.64-0.76), but it had a sensitivity of 0%. The researchers also tested the ability of the model to discriminate early neoplasia from no BE, and found an AUROC of 0.72 (95% CI, 0.67-0.77).

The researchers tested other models based on existing guidelines in the Houston area cohort and found that their model performed at the high end of the range when compared with those other models (AUROCs, 0.65-0.70 vs. 0.58-0.70). “While the predictive performance of Houston-BEST model is modest, it has much better discriminative ability compared to current societal clinical practice guidelines. However, the model may need to be further refined for lower risk (nonveteran) populations,” the authors wrote.

The strength of the model is that it relies on data found in the EHR. The researchers suggest that future studies should look employing the model alongside e-Trigger tools that can mine electronic clinical data to identify patients at risk for a missed diagnosis.

The authors reported no personal or financial conflicts of interest.
 

A new model that predicts Barrett’s esophagus (BE) risk relies on data that can be sourced from the electronic health record.

The tool was developed and validated by researchers seeking to improve early diagnosis of esophageal adenocarcinoma (EAC) through early detection of BE. Currently, 5-year survival from EAC is just 20%, and fewer than 30% of patients have curative options at diagnosis because of late-stage disease.

Several clinical guidelines recommend screening for BE in high-risk individuals. The trouble is that adherence is low: A meta-analysis of more than 33,000 patients found that 57% of newly diagnosed EAC patients had a simultaneous, first-time diagnosis of BE, which suggests missed screening opportunities. These patients also had higher probability of late-stage disease and worse mortality outcomes than patients who had a previous BE diagnosis. Low adherence to screening guidelines can be attributed to difficulties in implementation, as well as unsatisfactory outcomes in real-world settings. In a previous study, the researchers examined the efficacy of existing guidelines in diagnosing BE in a primary care population, and found all of these screening guidelines had a low area under the receiver operating curve ranging from 0.50 to 0.60.

The researchers sought to address these challenges in the current study published in Clinical Gastroenterology and Hepatology using a model development cohort of 274 patients with BE and 1,350 patients without BE. The patients were seen at Houston Veterans Affairs clinics between 2008 and 2012, and were between ages 40 and 80 years. The researchers included common risk factors identified among existing guidelines. The final model, Houston-BEST, incorporated sex, age, race/ethnicity, smoking status, body mass index, symptoms of gastroesophageal reflux disease (heartburn or reflux at least 1 day/week), and first-degree relative history of esophageal cancer.

The validation cohorts included patients from primary care clinics at the Houston VA who were undergoing screening colonoscopy (44 with BE, 469 without BE), as well as patients at the University of Michigan, Ann Arbor, or Ann Arbor VA clinics who presented for first esophagogastroduodenoscopy (71 with BE, 916 without BE).

In the development cohort, the researchers set an a priori threshold of predicted probability that corresponded to sensitivity of 90%; the threshold predicted probability of BE was 9.3% (AUROC, 0.69; 95% confidence interval, 0.66-0.72). The specificity was 39.9% (95% CI, 37.2%-42.5%). In the Houston area validation cohort, the model had a sensitivity of 84.1% (AUROC, 0.68; 95% CI, 0.60-0.76). The number needed to treat to detect a single BE case was 11.

Among the University of Michigan/Ann Arbor validation cohort, the model had an AUROC of 0.70 (95% CI, 0.64-0.76), but it had a sensitivity of 0%. The researchers also tested the ability of the model to discriminate early neoplasia from no BE, and found an AUROC of 0.72 (95% CI, 0.67-0.77).

The researchers tested other models based on existing guidelines in the Houston area cohort and found that their model performed at the high end of the range when compared with those other models (AUROCs, 0.65-0.70 vs. 0.58-0.70). “While the predictive performance of Houston-BEST model is modest, it has much better discriminative ability compared to current societal clinical practice guidelines. However, the model may need to be further refined for lower risk (nonveteran) populations,” the authors wrote.

The strength of the model is that it relies on data found in the EHR. The researchers suggest that future studies should look employing the model alongside e-Trigger tools that can mine electronic clinical data to identify patients at risk for a missed diagnosis.

The authors reported no personal or financial conflicts of interest.
 

A new model that predicts Barrett’s esophagus (BE) risk relies on data that can be sourced from the electronic health record.

The tool was developed and validated by researchers seeking to improve early diagnosis of esophageal adenocarcinoma (EAC) through early detection of BE. Currently, 5-year survival from EAC is just 20%, and fewer than 30% of patients have curative options at diagnosis because of late-stage disease.

Several clinical guidelines recommend screening for BE in high-risk individuals. The trouble is that adherence is low: A meta-analysis of more than 33,000 patients found that 57% of newly diagnosed EAC patients had a simultaneous, first-time diagnosis of BE, which suggests missed screening opportunities. These patients also had higher probability of late-stage disease and worse mortality outcomes than patients who had a previous BE diagnosis. Low adherence to screening guidelines can be attributed to difficulties in implementation, as well as unsatisfactory outcomes in real-world settings. In a previous study, the researchers examined the efficacy of existing guidelines in diagnosing BE in a primary care population, and found all of these screening guidelines had a low area under the receiver operating curve ranging from 0.50 to 0.60.

The researchers sought to address these challenges in the current study published in Clinical Gastroenterology and Hepatology using a model development cohort of 274 patients with BE and 1,350 patients without BE. The patients were seen at Houston Veterans Affairs clinics between 2008 and 2012, and were between ages 40 and 80 years. The researchers included common risk factors identified among existing guidelines. The final model, Houston-BEST, incorporated sex, age, race/ethnicity, smoking status, body mass index, symptoms of gastroesophageal reflux disease (heartburn or reflux at least 1 day/week), and first-degree relative history of esophageal cancer.

The validation cohorts included patients from primary care clinics at the Houston VA who were undergoing screening colonoscopy (44 with BE, 469 without BE), as well as patients at the University of Michigan, Ann Arbor, or Ann Arbor VA clinics who presented for first esophagogastroduodenoscopy (71 with BE, 916 without BE).

In the development cohort, the researchers set an a priori threshold of predicted probability that corresponded to sensitivity of 90%; the threshold predicted probability of BE was 9.3% (AUROC, 0.69; 95% confidence interval, 0.66-0.72). The specificity was 39.9% (95% CI, 37.2%-42.5%). In the Houston area validation cohort, the model had a sensitivity of 84.1% (AUROC, 0.68; 95% CI, 0.60-0.76). The number needed to treat to detect a single BE case was 11.

Among the University of Michigan/Ann Arbor validation cohort, the model had an AUROC of 0.70 (95% CI, 0.64-0.76), but it had a sensitivity of 0%. The researchers also tested the ability of the model to discriminate early neoplasia from no BE, and found an AUROC of 0.72 (95% CI, 0.67-0.77).

The researchers tested other models based on existing guidelines in the Houston area cohort and found that their model performed at the high end of the range when compared with those other models (AUROCs, 0.65-0.70 vs. 0.58-0.70). “While the predictive performance of Houston-BEST model is modest, it has much better discriminative ability compared to current societal clinical practice guidelines. However, the model may need to be further refined for lower risk (nonveteran) populations,” the authors wrote.

The strength of the model is that it relies on data found in the EHR. The researchers suggest that future studies should look employing the model alongside e-Trigger tools that can mine electronic clinical data to identify patients at risk for a missed diagnosis.

The authors reported no personal or financial conflicts of interest.
 

Lung cancer screening has been a success story in high-income countries, leading to a shift in diagnoses to earlier stages and a reduction in mortality among eligible groups.

A new report shows that middle- and low-income countries are being left out. “We do have good screening programs and some national ones, even in smaller European countries and in Canada, but in low- and middle-income countries where the mortality rates and the incidence of lung cancer is higher than in high-income countries, these programs are not implemented either at all or not implemented nationwide. This is a huge problem in the world,” said Milena Cavic, PhD, who presented the interim results on behalf of the diagnostics working group of the International Association for the Study of Lung Cancer early detection and screening committee at a press conference on Aug. 7 at the World Conference on Lung Cancer. Dr. Cavic is a senior research associate at the Institute for Oncology and Radiology of Serbia in Belgrade.

“It’s definitely a work in progress, and it’s also about raising awareness of the problem. In several parts of Asia, in Taiwan, in Korea, smoking is not the major, or at least, not the only reason for getting lung cancer. The other reasons are family history and also environmental factors like cooking fires, etc. So, the criteria we have for screening in Western countries are not one to one implementable in these countries,” said Rudolf Huber, MD, PhD, a respiratory physician at Ludwig Maximilian University of Munich and a coauthor of the report.

The report also pointed out the lack of recommendations for lung cancer screening in middle- and low-income countries. One approach would be to produce recommendations for countries with similar infrastructures and health resources, as well as primary risk factors such as smoking or cooking fires. “We have to adapt it to the various situations,” said Dr. Huber.

Another possibility is to rework existing recommendations for high income countries to adapt them to low- and middle-income countries. In the coming year, the working group will conduct a modeling study of Serbia, China, South Africa, and Columbia. It will look at population-specific and geographic factors from each country to produce country-specific models. “It will be interesting to see if these models will give us new recommendations for countries like this. So we can derive something from the high-income countries, but it will need to be adapted very, very much,” said Dr. Cavic.

The report highlighted some of the disparities between countries. CT scanners are far more common in high-income countries. Japan leads the way at 111.5 per million residents, followed by Australia at 70.2, Iceland at 47.6, and the United States at 44.9. At the other end is Columbia with 1.3, which trails Mexico at 5.9, Hungary at 9.4, and the United Kingdom at 9.5. However, the authors point out that there is no consensus on the optimum number of CT scanners per capita, since too few can lead to lack of access and too many can result in overuse. In fact, the greatest number of CT scans performed per capita was in the United States (278.5 per million), followed by Iceland (234.4), Japan (230.8), and Korea (228.1).

Lung cancer screening can be at odds with other health priorities, especially in low-income countries. These can include HIV, tuberculosis, and granulomatous diseases. But that could also provide an opportunity, according to Dr. Huber. “For example, in South Africa, tuberculosis programs are done by chest x-ray. We now have data that [allows us to] detect nodules by artificial intelligence, so one of the things we are thinking about is whether we could even use chest x-ray to get an earlier detection. At the end, it may be that in some countries it’s possible to do the classical CT screening, while in other countries we have to adapt to other options – probably chest x-ray using artificial intelligence or computer-aided diagnosis. And, then a consequent program for following up and managing the incidentally diagnosed nodules.”

The group is hoping to explore the environmental factors that could affect lung cancer risk in middle- and low-income countries. That is difficult to do, however, because smoking data can be hard to come by in many countries, and there is general uncertainty about what other risk factors may exist, though air pollution is a clear suspect. “It is something we are hoping to focus on in the future because there is a subgroup of individuals without a smoking history who are at high risk. It would be really good to find this high-risk population that should actually be screened in the future,” Dr. Cavic said.

Some countries have no data on lung cancer screening. For example, only South Africa is represented from Africa, and data is missing from many countries in Asia. The diagnostics working group of the IASLC early detection and screening committee has created a survey to gather information on the availability of lung cancer screening and its effect on diagnosis and treatment in countries throughout the world.

Dr. Cavic and Dr. Huber reported no relevant financial disclosures. The meeting was sponsored by the IASLC.

Lung cancer screening has been a success story in high-income countries, leading to a shift in diagnoses to earlier stages and a reduction in mortality among eligible groups.

A new report shows that middle- and low-income countries are being left out. “We do have good screening programs and some national ones, even in smaller European countries and in Canada, but in low- and middle-income countries where the mortality rates and the incidence of lung cancer is higher than in high-income countries, these programs are not implemented either at all or not implemented nationwide. This is a huge problem in the world,” said Milena Cavic, PhD, who presented the interim results on behalf of the diagnostics working group of the International Association for the Study of Lung Cancer early detection and screening committee at a press conference on Aug. 7 at the World Conference on Lung Cancer. Dr. Cavic is a senior research associate at the Institute for Oncology and Radiology of Serbia in Belgrade.

“It’s definitely a work in progress, and it’s also about raising awareness of the problem. In several parts of Asia, in Taiwan, in Korea, smoking is not the major, or at least, not the only reason for getting lung cancer. The other reasons are family history and also environmental factors like cooking fires, etc. So, the criteria we have for screening in Western countries are not one to one implementable in these countries,” said Rudolf Huber, MD, PhD, a respiratory physician at Ludwig Maximilian University of Munich and a coauthor of the report.

The report also pointed out the lack of recommendations for lung cancer screening in middle- and low-income countries. One approach would be to produce recommendations for countries with similar infrastructures and health resources, as well as primary risk factors such as smoking or cooking fires. “We have to adapt it to the various situations,” said Dr. Huber.

Another possibility is to rework existing recommendations for high income countries to adapt them to low- and middle-income countries. In the coming year, the working group will conduct a modeling study of Serbia, China, South Africa, and Columbia. It will look at population-specific and geographic factors from each country to produce country-specific models. “It will be interesting to see if these models will give us new recommendations for countries like this. So we can derive something from the high-income countries, but it will need to be adapted very, very much,” said Dr. Cavic.

The report highlighted some of the disparities between countries. CT scanners are far more common in high-income countries. Japan leads the way at 111.5 per million residents, followed by Australia at 70.2, Iceland at 47.6, and the United States at 44.9. At the other end is Columbia with 1.3, which trails Mexico at 5.9, Hungary at 9.4, and the United Kingdom at 9.5. However, the authors point out that there is no consensus on the optimum number of CT scanners per capita, since too few can lead to lack of access and too many can result in overuse. In fact, the greatest number of CT scans performed per capita was in the United States (278.5 per million), followed by Iceland (234.4), Japan (230.8), and Korea (228.1).

Lung cancer screening can be at odds with other health priorities, especially in low-income countries. These can include HIV, tuberculosis, and granulomatous diseases. But that could also provide an opportunity, according to Dr. Huber. “For example, in South Africa, tuberculosis programs are done by chest x-ray. We now have data that [allows us to] detect nodules by artificial intelligence, so one of the things we are thinking about is whether we could even use chest x-ray to get an earlier detection. At the end, it may be that in some countries it’s possible to do the classical CT screening, while in other countries we have to adapt to other options – probably chest x-ray using artificial intelligence or computer-aided diagnosis. And, then a consequent program for following up and managing the incidentally diagnosed nodules.”

The group is hoping to explore the environmental factors that could affect lung cancer risk in middle- and low-income countries. That is difficult to do, however, because smoking data can be hard to come by in many countries, and there is general uncertainty about what other risk factors may exist, though air pollution is a clear suspect. “It is something we are hoping to focus on in the future because there is a subgroup of individuals without a smoking history who are at high risk. It would be really good to find this high-risk population that should actually be screened in the future,” Dr. Cavic said.

Some countries have no data on lung cancer screening. For example, only South Africa is represented from Africa, and data is missing from many countries in Asia. The diagnostics working group of the IASLC early detection and screening committee has created a survey to gather information on the availability of lung cancer screening and its effect on diagnosis and treatment in countries throughout the world.

Dr. Cavic and Dr. Huber reported no relevant financial disclosures. The meeting was sponsored by the IASLC.

Lung cancer screening has been a success story in high-income countries, leading to a shift in diagnoses to earlier stages and a reduction in mortality among eligible groups.

A new report shows that middle- and low-income countries are being left out. “We do have good screening programs and some national ones, even in smaller European countries and in Canada, but in low- and middle-income countries where the mortality rates and the incidence of lung cancer is higher than in high-income countries, these programs are not implemented either at all or not implemented nationwide. This is a huge problem in the world,” said Milena Cavic, PhD, who presented the interim results on behalf of the diagnostics working group of the International Association for the Study of Lung Cancer early detection and screening committee at a press conference on Aug. 7 at the World Conference on Lung Cancer. Dr. Cavic is a senior research associate at the Institute for Oncology and Radiology of Serbia in Belgrade.

“It’s definitely a work in progress, and it’s also about raising awareness of the problem. In several parts of Asia, in Taiwan, in Korea, smoking is not the major, or at least, not the only reason for getting lung cancer. The other reasons are family history and also environmental factors like cooking fires, etc. So, the criteria we have for screening in Western countries are not one to one implementable in these countries,” said Rudolf Huber, MD, PhD, a respiratory physician at Ludwig Maximilian University of Munich and a coauthor of the report.

The report also pointed out the lack of recommendations for lung cancer screening in middle- and low-income countries. One approach would be to produce recommendations for countries with similar infrastructures and health resources, as well as primary risk factors such as smoking or cooking fires. “We have to adapt it to the various situations,” said Dr. Huber.

Another possibility is to rework existing recommendations for high income countries to adapt them to low- and middle-income countries. In the coming year, the working group will conduct a modeling study of Serbia, China, South Africa, and Columbia. It will look at population-specific and geographic factors from each country to produce country-specific models. “It will be interesting to see if these models will give us new recommendations for countries like this. So we can derive something from the high-income countries, but it will need to be adapted very, very much,” said Dr. Cavic.

The report highlighted some of the disparities between countries. CT scanners are far more common in high-income countries. Japan leads the way at 111.5 per million residents, followed by Australia at 70.2, Iceland at 47.6, and the United States at 44.9. At the other end is Columbia with 1.3, which trails Mexico at 5.9, Hungary at 9.4, and the United Kingdom at 9.5. However, the authors point out that there is no consensus on the optimum number of CT scanners per capita, since too few can lead to lack of access and too many can result in overuse. In fact, the greatest number of CT scans performed per capita was in the United States (278.5 per million), followed by Iceland (234.4), Japan (230.8), and Korea (228.1).

Lung cancer screening can be at odds with other health priorities, especially in low-income countries. These can include HIV, tuberculosis, and granulomatous diseases. But that could also provide an opportunity, according to Dr. Huber. “For example, in South Africa, tuberculosis programs are done by chest x-ray. We now have data that [allows us to] detect nodules by artificial intelligence, so one of the things we are thinking about is whether we could even use chest x-ray to get an earlier detection. At the end, it may be that in some countries it’s possible to do the classical CT screening, while in other countries we have to adapt to other options – probably chest x-ray using artificial intelligence or computer-aided diagnosis. And, then a consequent program for following up and managing the incidentally diagnosed nodules.”

The group is hoping to explore the environmental factors that could affect lung cancer risk in middle- and low-income countries. That is difficult to do, however, because smoking data can be hard to come by in many countries, and there is general uncertainty about what other risk factors may exist, though air pollution is a clear suspect. “It is something we are hoping to focus on in the future because there is a subgroup of individuals without a smoking history who are at high risk. It would be really good to find this high-risk population that should actually be screened in the future,” Dr. Cavic said.

Some countries have no data on lung cancer screening. For example, only South Africa is represented from Africa, and data is missing from many countries in Asia. The diagnostics working group of the IASLC early detection and screening committee has created a survey to gather information on the availability of lung cancer screening and its effect on diagnosis and treatment in countries throughout the world.

Dr. Cavic and Dr. Huber reported no relevant financial disclosures. The meeting was sponsored by the IASLC.

A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

A new study finds that patients with screen-detected lung cancer are at increased risk for a second primary lung cancer diagnosis, with about half occurring within 6 months of the first diagnosis. More than 80% of second primary cancers diagnosed within 2 years were stage 1, compared with about 25% when diagnosed more than 5 years later.

“With the growing adoption of lung cancer screening, more patients are being diagnosed with early-stage lung cancers and are able to achieve excellent long-term survival. After lung cancer diagnosis, these patients remain at high risk of developing a second primary lung cancer. The incidence, timing, and survival of second primary lung cancers is not well understood, particularly in a patient population with initial primary lung cancers detected via lung cancer screening,” said Alexandra Potter, who is a study coauthor.

The results were presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer sponsored by the International Association for the Study of Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

A 2012 study analyzed data from the SEER database and found that lung cancer survivors had a four- to sixfold increase in the risk of developing a second primary lung cancer, compared with the risk of lung cancer in the general population after adjusting for sex, age, race, and calendar year. “That study demonstrated that second primary lung cancers are an important risk among lung cancer survivors. However, it did not evaluate patients diagnosed with initial lung cancers detected via lung cancer screening. Thus, the incidence, timing, characteristics, and survival of lung cancers diagnosed among patients diagnosed with initial lung cancers detected via lung cancer screening remain unknown,” said Ms. Potter, who is a research assistant at Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

To address that question, the researchers used data from the National Lung Screening Trial, which compared low-dose computed tomography to chest x-ray and found that the former led to a 15%-20% lower risk of death. The new analysis included 1,405 patients who were diagnosed with stage I-III lung cancer and treated between 2002 and 2009. Of these patients, 5.8% went on to be diagnosed with a second primary lung cancer, at a rate of 1%-2% per year. Of the second lung cancers, 54.9% were synchronous, occurring within 6 months of the diagnosis, and 45.1% were metachronous, occurring later than 6 months; 65% of synchronous secondary cancers and 81% of metachronous cancers were diagnosed at stage I; 24% of synchronous and 14% of metachronous were stage III (P = .25). The median time to diagnosis of metachronous lung cancers was 2.7 years, and 27% of the second primary tumors were diagnosed 4 or more years after the first diagnosis.

Among those with synchronous tumors, 5- and 10-year survival rates were 55.2% and 39.5%. The rates were 90.0% and 30.8% among metachronous tumors, respectively. Ms. Potter emphasized that most patients with second primary cancer were diagnosed at stage I, suggesting that it is very possible to catch these cancers early. But patients who were diagnosed with a second primary tumor 4 or more years after their first diagnosis had a greater likelihood of later-stage second cancer. Medical societies generally recommend CT screening surveillance every 6 months for 2 years following a lung cancer diagnosis, then annually thereafter. The greater frequency of later-stage cancer detected after 4 years suggests that surveillance may be flagging as time goes on. “These data highlight the importance of lifelong follow up after initial lung cancer diagnosis,” said Ms. Potter.

She also emphasized the importance of smoking cessation and ongoing abstinence following a diagnosis of lung cancer. “About 70% of patients in the NLST who developed second primary lung cancer currently smoked at the time of entry into the trial. Smoking cessation can help reduce patients’ risk of developing second primary lung cancers,” she said. Ms. Potter has no relevant financial disclosures.

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.

SAN DIEGO – In 1906, a neuroanatomist and psychiatrist named Alois Alzheimer examined the brain of a 50-year-old woman whom he had treated for paranoia, sleep and memory problems, aggression, and confusion. His autopsy revealed plaques and tangles in her brain. The most common components of these tangles are beta-amyloid peptide (A-beta) and the microtubule binding protein tau. Over the past few decades, that finding has launched many clinical development programs and dozens of clinical trials.

To date, all but one program has failed. In 2021, amidst much controversy, FDA granted accelerated approval to Biogen’s Aduhelm, which effectively clears A-beta and tau deposits from patients’ brains. The problem is that the clinical benefit is small, and uptake has been so low that the company was forced to abandon a planned postmarketing observational trial.
 

Chasing the wrong target?

At a session at the 2022 Alzheimer’s Association International Conference, Raymond J. Tesi, MD, rather forcefully refuted that approach. “Amyloid and tau therapies have had 20 years to prove themselves. We have multiple cases where we’ve been able to decrease amyloid, maybe not so much tau, but certainly amyloid, and the benefits are mild at best. So I think that the Alzheimer’s drug development community, whether you look at the NIH, whether you look at academia, whether you look at biopharma, has focused on a target that has not proven itself, and it’s time to move on,” said Dr. Tesi, who is president, CEO, and chief medical officer at INmune Bio.

Later in the session, researchers presented strategies to counter Alzheimer’s disease and other neurodegenerative conditions using strategies including modulation of metabolism and inflammation, support of brain homeostasis, and suppression of a broader range of neurotoxic proteins.

One audience member defended the potential importance of A-beta and tau, especially in astrogliosis, which is a reaction to stress by astrocytes that attempts to limit tissue damage. The questioner suggested that it was still important to measure the effect of a novel drug on A-beta and tau. “What would be the cause of the reactive astrogliosis and microglia activation, if we are not giving a damn about amyloid and tau?” he asked.

After a bit of back and forth, Dr. Tesi replied: “We both have a religious belief here, and sooner or later we’ll get the answer.”
 

A diverse clinical pipeline

The session itself focused on four companies, including Dr. Tesi’s INmune Bio, which have drugs with alternative mechanisms entering the advanced stages of clinical development. That’s good news, according to Heather Snyder, PhD, who is vice president of Medical & Scientific Relations at the Alzheimer’s Association. “One of the things that I think is really important is the diversity of what’s in the clinical pipeline, and it’s not just in the very beginning anymore. We’re seeing [companies] now reporting phase 2 [studies] and planning their next stage. That’s something that as a field we should be excited about. As we understand more and more about the biology, we’re now seeing that translating into clinical trials and we’re seeing that translate through the clinical pipeline of development,” said Dr. Snyder in an interview.

Targeting neuroinflammation

Dr. Tesi kicked off the session describing INmune Bio’s focus on neuroinflammation. The company’s drug candidate targets soluble tumor necrosis factor (TNF), which the company believes is a direct cause of Alzheimer’s disease through promotion of inflammation. He noted that TNF is a primary mediator of inflammation in rheumatoid arthritis, and patients with RA have an eightfold increased risk of developing Alzheimer’s disease, compared with the general population, while patients with RA who are taking anti-TNF medication have a 60% lower risk than the general population.

The company’s TNF inhibitor XPro is also unique in that it induces remyelination in mice, while other TNF inhibitors potentially “abuse” the brain by causing demyelination. Earlier research showed that it reduces neuroinflammation, improves nerve cell survival, and improves synaptic function. The company is conducting two phase 2 clinical trials, one in patients with mild cognitive impairment (MCI) and one in mild Alzheimer’s disease. They also use the MCI Alzheimer’s Cognitive Composite (EMACC) tool for assessing outcomes rather than the more commonly used Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). “ADAS-Cog is like trying to make sushi with an axe. It is designed for moderate to severe disease, and trying to use it for mild (Alzheimer’s disease) or MCI is a mistake. EMACC is purpose built for mild [AD] and MCI patients,” said Dr. Tesi.
 

Maintaining homeostatis

Next, Hans Moebius, MD, PhD, chief medical officer of Athira Pharma, described his company’s focus on the hepatocyte growth factor (HGF) receptor, also known as tyrosine kinase MET (HGF/MET). It plays an important role in brain development and homeostasis, and it is expressed at lower levels in the frontal cortex and hippocampus of patients with Alzheimer’s disease. The company’s small-molecule drug candidate boosts the HGF/MET pathway, leading to downstream neuroprotection and neurotrophic effects. It also promotes formation of new synapses.

Dr. Moebius presented the results of a phase 2 trial showing that the drug, called fosgonimeton, led to significant cognitive improvement compared with placebo. The company is conducting a phase 3 clinical trial.
 

Type 3 diabetes?

In his talk, John Didsbury, PhD, founder and CEO of T3D Therapeutics, framed Alzheimer’s disease as a disease of metabolic dysfunction. He believes alterations to glucose and lipids in the brain cause structural changes that lead to symptoms. He pointed out that the strongest genetic Alzheimer’s disease risk factor is a mutant form of the lipid transport protein APOE4.

“What we have is dysregulated glucose energy metabolism and lipid metabolism that really cause, in our mind, the structural event changes and the stress event changes – plaques, tangles, inflammation, etc. – but these events perpetuate the dysregulated metabolism. It’s a massive positive feedback loop that many have called type 3 diabetes – a brain-specific form of diabetes,” said Dr. Didsbury.

The company’s approach is to use systems biology to identify a drug target that can bypass multiple aberrant insulin signaling pathways. Its drug candidate regulates the expression of multiple genes involved in glucose metabolism. Dr. Didsbury presented interim results from a phase 2 study showing improvement over placebo.
 

Focusing on neurotoxic proteins

The final presentation of the session was by Maria Maccecchini, PhD, founder, president, and CEO of Annovis Bio. The company’s drug, buntanetap, reduces expression of a range of neurotoxic proteins. The downstream effects include restoration of axonal transport, reduction of inflammation, and protection of nerve cells. The company believes that Alzheimer’s disease results from acute and chronic stress events that lead to high levels of neurotoxic proteins, which include A-beta, tau, alpha-synuclein, and TDP43. The proteins aren’t just players in Alzheimer’s disease – they are present in abnormal levels in Parkinson’s disease and a range of other brain pathologies.

“In the brain of an Alzheimer’s and of a Parkinson’s [patient], you’re going to find all four proteins. You’ll find them in different concentrations, at different time points, in different brain areas. If you just remove one, you still have the other three that cause impairment in axonal transport, and that leads to inflammation that leads to neurodegeneration,” said Dr. Maccecchini.

The company’s drug manages to reduce levels of all four proteins by binding to a segment of messenger RNA (mRNA) shared by all of them. mRNA serves as a template for protein synthesis. Under normal conditions, the neurotoxic protein concentrations are kept low because the mRNA segment remains bound to a regulatory protein that prevents synthesis from occurring. However, when stress leads to high levels of iron, this regulatory binding protein releases the mRNA segment (along with the rest of the mRNA). The freed mRNA becomes available to the cell’s protein synthesis machinery, which starts producing high levels of neurotoxic proteins. Annovis Bio’s drug improves the ability of the regulatory protein to bind to the mRNA segment, preventing protein expression even in high-iron conditions. It works on all four neurotoxic proteins because they all have the regulatory segment in their mRNA.

The drug led to improvements in phase 2 studies of Alzheimer’s disease and Parkinson’s disease, and the company is currently recruiting for a phase 3 study in Parkinson’s disease and a phase 2/3 dose-response study in Alzheimer’s disease.
 

Combination treatments for a complex disease

Taken together, the presentations provided a snapshot of the post–A-beta/tau Alzheimer’s development world, and the future could be messy. Alzheimer’s disease and other dementias are likely to require combination treatments, according to Dr. Snyder. “This is a complex disease, not just Alzheimer’s but other dementias. It’s not going to be a single drug, a single target. It’s going to require some type of combinatorial approach, whether that be with medication and lifestyle interventions, or risk reduction, and different medications,” she said.

The latest results are good news for that approach: “We’re seeing that maturation of the science in these trials,” said Dr. Snyder.

Cheng Fang, PhD, senior vice president of research and development at Annovis Bio, agreed with that sentiment. “I believe [Alzheimer’s disease and dementia] is a very complicated disease. I always call them diseases instead of a disease because it’s a spectrum. I don’t believe one drug can cure them all, as much as I am confident in our drug. I think it’s extremely important to encourage this kind of diverse thinking,” said Dr. Fang.

Dr. Snyder has no relevant financial disclosures. Dr. Tesi, Dr. Moebius, Dr. Didsbury, Dr. Maccecchini, and Dr. Fang are employees and in some cases stockholders of their respective companies.

Advances have been made in earlier diagnosis and better overall survival among older patients with lung cancer, but younger adults have not experienced the same benefit, according to a new study.

The improvements in patients aged 55-80 are likely associated with the introduction in 2013 of low dose computed tomography lung cancer screening.

“It was unknown whether young adults diagnosed with lung cancer, who are ineligible for screening, have experienced a similar shift to earlier stages of lung cancer. While previous studies have shown that young adults diagnosed with lung cancer have distinct tumor characteristics and survival compared to older adults diagnosed with lung cancer, no study has examined whether recent improvements in early diagnosis and survival among older adults with lung cancer extend to younger adults diagnosed with lung cancer,” study coauthor Alexandra Potter told this news organization.

The study was presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

The difference might be explained by difference in tumor biology, as younger adults are often diagnosed with more aggressive cancers. Other factors include delayed diagnosis and a lack of early detection strategies for this population. Older patients likely benefited from the onset of lung cancer screening, as well as an increase in non-screening chest CT use in hospital settings, which may lead to more incidental diagnoses, according to Ms. Potter, a research assistant Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

Investigators found that about three in four lung cancer diagnoses among adults aged 20-29 were stage IV disease, and only 8% in that group were stage I. “I was surprised” by the high frequency of stage IV cancer, said Ms. Potter. “I would also highlight that there has been no improvement in early diagnosis among patients aged 20-49 during the study period,” she added.

And although it is often assumed that patients diagnosed at a younger age have better survival, the study painted a grim picture: Five-year survival was 10%-15% among patients diagnosed at age 20-49 with stage IV cancer. “More research is needed to better understand the risk factors, diagnosis, treatment, and survival of lung cancer in young adults,” Ms. Potter said.

There are strategies in development, including biomarkers, machine learning analysis of CT scans, and risk prediction models, but none have yet borne fruit. “Once we are able to [identify high-risk young adults], this will allow us to offer lung cancer screening to these young adults who are at high risk for developing lung cancer,” Ms. Potter said.
 

Study methodology

The researchers analyzed data from the United States Cancer Statistics (USCS) database and the National Cancer Database (NCDB). They included patients aged 20-79 diagnosed with non–small cell lung cancer (NSCLC) between 2010 and 2018. The study included 1,328 individuals aged 20-29, 5,682 men and women aged 30-39, 39,323 individuals aged 40-49, 202,709 aged 50-59, 410,482 aged 60-69, and 447,366 aged 70-79.

Stage IV diagnoses were most common in the youngest group (76% versus 8% stage I), and steadily declined with age 30-39 (70% versus 10%), age 40-49 (60% versus 14%), 50-59 (52%versus 19%), 60-69 (45% versus 25%), and 70-79 (40% versus 25%; P < .001). The trend reversed among patients aged 80-89, with 45% of patients diagnosed with stage IV cancer, though the rising trend of stage I diagnoses continued at 29%. Between 2010 and 2018, there was a statistically significant increase in stage IV diagnoses among those aged 40-49, and a decrease among those aged 50-59, 60-69, and 70-79.

Five-year overall survival was lowest among patients aged 20-29 at 20%. It was 27%-28% among each 10-year age group up to age 69, then dropped to 24% among those aged 70-79 (P < .001).

The study was limited by a lack of data on disease-free or recurrence-free survival, as well as use of biomarkers or targeted therapy. Ms. Potter has no relevant financial disclosures. The conference was sponsored by the International Association for the Study of Lung Cancer.

Advances have been made in earlier diagnosis and better overall survival among older patients with lung cancer, but younger adults have not experienced the same benefit, according to a new study.

The improvements in patients aged 55-80 are likely associated with the introduction in 2013 of low dose computed tomography lung cancer screening.

“It was unknown whether young adults diagnosed with lung cancer, who are ineligible for screening, have experienced a similar shift to earlier stages of lung cancer. While previous studies have shown that young adults diagnosed with lung cancer have distinct tumor characteristics and survival compared to older adults diagnosed with lung cancer, no study has examined whether recent improvements in early diagnosis and survival among older adults with lung cancer extend to younger adults diagnosed with lung cancer,” study coauthor Alexandra Potter told this news organization.

The study was presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

The difference might be explained by difference in tumor biology, as younger adults are often diagnosed with more aggressive cancers. Other factors include delayed diagnosis and a lack of early detection strategies for this population. Older patients likely benefited from the onset of lung cancer screening, as well as an increase in non-screening chest CT use in hospital settings, which may lead to more incidental diagnoses, according to Ms. Potter, a research assistant Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

Investigators found that about three in four lung cancer diagnoses among adults aged 20-29 were stage IV disease, and only 8% in that group were stage I. “I was surprised” by the high frequency of stage IV cancer, said Ms. Potter. “I would also highlight that there has been no improvement in early diagnosis among patients aged 20-49 during the study period,” she added.

And although it is often assumed that patients diagnosed at a younger age have better survival, the study painted a grim picture: Five-year survival was 10%-15% among patients diagnosed at age 20-49 with stage IV cancer. “More research is needed to better understand the risk factors, diagnosis, treatment, and survival of lung cancer in young adults,” Ms. Potter said.

There are strategies in development, including biomarkers, machine learning analysis of CT scans, and risk prediction models, but none have yet borne fruit. “Once we are able to [identify high-risk young adults], this will allow us to offer lung cancer screening to these young adults who are at high risk for developing lung cancer,” Ms. Potter said.
 

Study methodology

The researchers analyzed data from the United States Cancer Statistics (USCS) database and the National Cancer Database (NCDB). They included patients aged 20-79 diagnosed with non–small cell lung cancer (NSCLC) between 2010 and 2018. The study included 1,328 individuals aged 20-29, 5,682 men and women aged 30-39, 39,323 individuals aged 40-49, 202,709 aged 50-59, 410,482 aged 60-69, and 447,366 aged 70-79.

Stage IV diagnoses were most common in the youngest group (76% versus 8% stage I), and steadily declined with age 30-39 (70% versus 10%), age 40-49 (60% versus 14%), 50-59 (52%versus 19%), 60-69 (45% versus 25%), and 70-79 (40% versus 25%; P < .001). The trend reversed among patients aged 80-89, with 45% of patients diagnosed with stage IV cancer, though the rising trend of stage I diagnoses continued at 29%. Between 2010 and 2018, there was a statistically significant increase in stage IV diagnoses among those aged 40-49, and a decrease among those aged 50-59, 60-69, and 70-79.

Five-year overall survival was lowest among patients aged 20-29 at 20%. It was 27%-28% among each 10-year age group up to age 69, then dropped to 24% among those aged 70-79 (P < .001).

The study was limited by a lack of data on disease-free or recurrence-free survival, as well as use of biomarkers or targeted therapy. Ms. Potter has no relevant financial disclosures. The conference was sponsored by the International Association for the Study of Lung Cancer.

Advances have been made in earlier diagnosis and better overall survival among older patients with lung cancer, but younger adults have not experienced the same benefit, according to a new study.

The improvements in patients aged 55-80 are likely associated with the introduction in 2013 of low dose computed tomography lung cancer screening.

“It was unknown whether young adults diagnosed with lung cancer, who are ineligible for screening, have experienced a similar shift to earlier stages of lung cancer. While previous studies have shown that young adults diagnosed with lung cancer have distinct tumor characteristics and survival compared to older adults diagnosed with lung cancer, no study has examined whether recent improvements in early diagnosis and survival among older adults with lung cancer extend to younger adults diagnosed with lung cancer,” study coauthor Alexandra Potter told this news organization.

The study was presented by Chi-Fu Jeffrey Yang, MD, at a press conference held at the World Conference on Lung Cancer. Dr. Yang is a thoracic surgeon at Massachusetts General Hospital, Boston.

The difference might be explained by difference in tumor biology, as younger adults are often diagnosed with more aggressive cancers. Other factors include delayed diagnosis and a lack of early detection strategies for this population. Older patients likely benefited from the onset of lung cancer screening, as well as an increase in non-screening chest CT use in hospital settings, which may lead to more incidental diagnoses, according to Ms. Potter, a research assistant Massachusetts General Hospital and president of the American Lung Cancer Screening Initiative.

Investigators found that about three in four lung cancer diagnoses among adults aged 20-29 were stage IV disease, and only 8% in that group were stage I. “I was surprised” by the high frequency of stage IV cancer, said Ms. Potter. “I would also highlight that there has been no improvement in early diagnosis among patients aged 20-49 during the study period,” she added.

And although it is often assumed that patients diagnosed at a younger age have better survival, the study painted a grim picture: Five-year survival was 10%-15% among patients diagnosed at age 20-49 with stage IV cancer. “More research is needed to better understand the risk factors, diagnosis, treatment, and survival of lung cancer in young adults,” Ms. Potter said.

There are strategies in development, including biomarkers, machine learning analysis of CT scans, and risk prediction models, but none have yet borne fruit. “Once we are able to [identify high-risk young adults], this will allow us to offer lung cancer screening to these young adults who are at high risk for developing lung cancer,” Ms. Potter said.
 

Study methodology

The researchers analyzed data from the United States Cancer Statistics (USCS) database and the National Cancer Database (NCDB). They included patients aged 20-79 diagnosed with non–small cell lung cancer (NSCLC) between 2010 and 2018. The study included 1,328 individuals aged 20-29, 5,682 men and women aged 30-39, 39,323 individuals aged 40-49, 202,709 aged 50-59, 410,482 aged 60-69, and 447,366 aged 70-79.

Stage IV diagnoses were most common in the youngest group (76% versus 8% stage I), and steadily declined with age 30-39 (70% versus 10%), age 40-49 (60% versus 14%), 50-59 (52%versus 19%), 60-69 (45% versus 25%), and 70-79 (40% versus 25%; P < .001). The trend reversed among patients aged 80-89, with 45% of patients diagnosed with stage IV cancer, though the rising trend of stage I diagnoses continued at 29%. Between 2010 and 2018, there was a statistically significant increase in stage IV diagnoses among those aged 40-49, and a decrease among those aged 50-59, 60-69, and 70-79.

Five-year overall survival was lowest among patients aged 20-29 at 20%. It was 27%-28% among each 10-year age group up to age 69, then dropped to 24% among those aged 70-79 (P < .001).

The study was limited by a lack of data on disease-free or recurrence-free survival, as well as use of biomarkers or targeted therapy. Ms. Potter has no relevant financial disclosures. The conference was sponsored by the International Association for the Study of Lung Cancer.

In a randomized, controlled trial, endoscopic sleeve gastroplasty (ESG) combined with lifestyle modifications was safe and effective for weight loss among individuals with class I and class II obesity, compared with lifestyle modifications alone.

“Lifestyle modifications and pharmacological therapy have several limitations, and the use of bariatric surgery is hampered by its invasive nature and patient perceptions,” the study authors wrote. ESG is a minimally invasive, reversible, organ-sparing bariatric procedure that might be able to fill those care gaps, they explained.

Previous retrospective studies have suggested that ESG is effective, and a meta-analysis of 1,772 patients found an average total body weight loss of 15.1% at 6 months (95% confidence interval, 14.3%-16.0%) and 16.5% at 12 months (95% CI, 15.2%-17.8%). However, according to the authors of the current study, known as MERIT and published in the Lancet, there have been no randomized clinical trials investigating ESG's efficacy to date.

“[This is] the kind of study that we have been looking forward to. The outcomes were very impressive,” said Danny Issa, MD, who was asked to comment on the study. He is a clinical assistant professor of medicine at the University of California, Los Angeles. meta-analysis of 1,772 patients found an average total body weight loss of 15.1% at 6 months (95% confidence interval, 14.3%-16.0%) and 16.5% at 12 months (95% CI, 15.2%-17.8%).

Understanding the study and its results

Between December 2017 and June 2019, the researchers randomized 209 participants to ESG plus lifestyle modification or lifestyle modification only, which served as the control. The mean age was 47.3 in the ESG group (88% female) and 45.7 in the control group (84% female). The mean body mass index (BMI) was 35.5 kg/m² in the ESG group and 35.7 among controls.

After 1 year, the intervention group had a mean percentage of excess weight loss (EWL) of 49.2% , compared with 3.2% for the control group (P < .0001). The mean percentage of total body weight lost was 13.6% in the ESG group and 0.8% in the control group (P < .0001). After adjustment for age, sex, type 2 diabetes, hypertension, and baseline BMI, the ESG group had a mean difference of excess weight loss of 44.7% (95% CI, 37.5%-51.9%) and a mean difference of total weight loss of 12.6% (95% CI, 10.7%-14.5%), compared with the control group at 52 weeks. At 52 weeks, 77% of the ESG group had at least a 25% excess weight loss, which was the secondary endpoint, compared with 12% of the control group (P < .0001).

Overall, 80% of the ESG group had an improvement in at least one metabolic comorbidity, while 12% experienced a worsening. Among the control group, 45% had an improvement and 50% worsened. Among 27 patients in the treatment group with diabetes, 93% experienced an improvement in hemoglobin A1c levels, compared with 15% of patients with diabetes in the control group. Similarly among patients with hypertension, 60% in the intervention group had an improvement, compared with 40% of controls. Of those with metabolic syndrome, 83% improved after undergoing surgery, compared with 35% of controls.

At 2 years, 68% of the ESG group who achieved a 25% EWL continued to have at least 25% EWL; 2% in the treatment group had a serious ESG-related adverse event, but there was no mortality or need for intensive care or follow-up surgery.
 

Aiming for level I evidence

“The results are very encouraging, so I think it’s good news for the field of bariatric endoscopy. I think it’s going to provide more confidence to patients and physicians, and for new trainees who are interested in this field, I think it’s going to inspire them,” said Shailendra Singh, MD, who was asked to comment on the study. Dr. Singh is an associate professor of medicine and director of bariatric medicine at West Virginia University, Morgantown.

The study could also improve insurance coverage of the procedure, said Dr. Singh. “I think this study will help us reach out to the payers and give them the data behind this because they always look for level I evidence. ESG is a relatively new endoscopic procedure; I think this is a step forward in that direction,” he said.

The study underlines the applicability of the procedure to patients who don’t want more invasive surgery, or who can’t tolerate some of the higher efficacy medications that are increasingly available.

It is also just one of various options for obesity treatment, which are increasingly being used in combination, according to Avlin Imaeda, MD. “Just like we see in hypertension, where you progressively add more and more medications, I think we’re going to see obesity treatment go that way too. I see this as adding choice for patients and adding to this potentially multimodal approach,” said Dr. Imaeda, an associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study.

The study authors report various financial relationships, including some with Apollo Endosurgery, which funded this study. Dr. Issa and Dr. Imaeda have no relevant financial disclosures. Dr. Singh is a consultant for Apollo Endosurgery.

This article was updated Aug. 18, 2022.

In a randomized, controlled trial, endoscopic sleeve gastroplasty (ESG) combined with lifestyle modifications was safe and effective for weight loss among individuals with class I and class II obesity, compared with lifestyle modifications alone.

“Lifestyle modifications and pharmacological therapy have several limitations, and the use of bariatric surgery is hampered by its invasive nature and patient perceptions,” the study authors wrote. ESG is a minimally invasive, reversible, organ-sparing bariatric procedure that might be able to fill those care gaps, they explained.

Previous retrospective studies have suggested that ESG is effective, and a meta-analysis of 1,772 patients found an average total body weight loss of 15.1% at 6 months (95% confidence interval, 14.3%-16.0%) and 16.5% at 12 months (95% CI, 15.2%-17.8%). However, according to the authors of the current study, known as MERIT and published in the Lancet, there have been no randomized clinical trials investigating ESG's efficacy to date.

“[This is] the kind of study that we have been looking forward to. The outcomes were very impressive,” said Danny Issa, MD, who was asked to comment on the study. He is a clinical assistant professor of medicine at the University of California, Los Angeles. meta-analysis of 1,772 patients found an average total body weight loss of 15.1% at 6 months (95% confidence interval, 14.3%-16.0%) and 16.5% at 12 months (95% CI, 15.2%-17.8%).

Understanding the study and its results

Between December 2017 and June 2019, the researchers randomized 209 participants to ESG plus lifestyle modification or lifestyle modification only, which served as the control. The mean age was 47.3 in the ESG group (88% female) and 45.7 in the control group (84% female). The mean body mass index (BMI) was 35.5 kg/m² in the ESG group and 35.7 among controls.

After 1 year, the intervention group had a mean percentage of excess weight loss (EWL) of 49.2% , compared with 3.2% for the control group (P < .0001). The mean percentage of total body weight lost was 13.6% in the ESG group and 0.8% in the control group (P < .0001). After adjustment for age, sex, type 2 diabetes, hypertension, and baseline BMI, the ESG group had a mean difference of excess weight loss of 44.7% (95% CI, 37.5%-51.9%) and a mean difference of total weight loss of 12.6% (95% CI, 10.7%-14.5%), compared with the control group at 52 weeks. At 52 weeks, 77% of the ESG group had at least a 25% excess weight loss, which was the secondary endpoint, compared with 12% of the control group (P < .0001).

Overall, 80% of the ESG group had an improvement in at least one metabolic comorbidity, while 12% experienced a worsening. Among the control group, 45% had an improvement and 50% worsened. Among 27 patients in the treatment group with diabetes, 93% experienced an improvement in hemoglobin A1c levels, compared with 15% of patients with diabetes in the control group. Similarly among patients with hypertension, 60% in the intervention group had an improvement, compared with 40% of controls. Of those with metabolic syndrome, 83% improved after undergoing surgery, compared with 35% of controls.

At 2 years, 68% of the ESG group who achieved a 25% EWL continued to have at least 25% EWL; 2% in the treatment group had a serious ESG-related adverse event, but there was no mortality or need for intensive care or follow-up surgery.
 

Aiming for level I evidence

“The results are very encouraging, so I think it’s good news for the field of bariatric endoscopy. I think it’s going to provide more confidence to patients and physicians, and for new trainees who are interested in this field, I think it’s going to inspire them,” said Shailendra Singh, MD, who was asked to comment on the study. Dr. Singh is an associate professor of medicine and director of bariatric medicine at West Virginia University, Morgantown.

The study could also improve insurance coverage of the procedure, said Dr. Singh. “I think this study will help us reach out to the payers and give them the data behind this because they always look for level I evidence. ESG is a relatively new endoscopic procedure; I think this is a step forward in that direction,” he said.

The study underlines the applicability of the procedure to patients who don’t want more invasive surgery, or who can’t tolerate some of the higher efficacy medications that are increasingly available.

It is also just one of various options for obesity treatment, which are increasingly being used in combination, according to Avlin Imaeda, MD. “Just like we see in hypertension, where you progressively add more and more medications, I think we’re going to see obesity treatment go that way too. I see this as adding choice for patients and adding to this potentially multimodal approach,” said Dr. Imaeda, an associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study.

The study authors report various financial relationships, including some with Apollo Endosurgery, which funded this study. Dr. Issa and Dr. Imaeda have no relevant financial disclosures. Dr. Singh is a consultant for Apollo Endosurgery.

This article was updated Aug. 18, 2022.

In a randomized, controlled trial, endoscopic sleeve gastroplasty (ESG) combined with lifestyle modifications was safe and effective for weight loss among individuals with class I and class II obesity, compared with lifestyle modifications alone.

“Lifestyle modifications and pharmacological therapy have several limitations, and the use of bariatric surgery is hampered by its invasive nature and patient perceptions,” the study authors wrote. ESG is a minimally invasive, reversible, organ-sparing bariatric procedure that might be able to fill those care gaps, they explained.

Previous retrospective studies have suggested that ESG is effective, and a meta-analysis of 1,772 patients found an average total body weight loss of 15.1% at 6 months (95% confidence interval, 14.3%-16.0%) and 16.5% at 12 months (95% CI, 15.2%-17.8%). However, according to the authors of the current study, known as MERIT and published in the Lancet, there have been no randomized clinical trials investigating ESG's efficacy to date.

“[This is] the kind of study that we have been looking forward to. The outcomes were very impressive,” said Danny Issa, MD, who was asked to comment on the study. He is a clinical assistant professor of medicine at the University of California, Los Angeles. meta-analysis of 1,772 patients found an average total body weight loss of 15.1% at 6 months (95% confidence interval, 14.3%-16.0%) and 16.5% at 12 months (95% CI, 15.2%-17.8%).

Understanding the study and its results

Between December 2017 and June 2019, the researchers randomized 209 participants to ESG plus lifestyle modification or lifestyle modification only, which served as the control. The mean age was 47.3 in the ESG group (88% female) and 45.7 in the control group (84% female). The mean body mass index (BMI) was 35.5 kg/m² in the ESG group and 35.7 among controls.

After 1 year, the intervention group had a mean percentage of excess weight loss (EWL) of 49.2% , compared with 3.2% for the control group (P < .0001). The mean percentage of total body weight lost was 13.6% in the ESG group and 0.8% in the control group (P < .0001). After adjustment for age, sex, type 2 diabetes, hypertension, and baseline BMI, the ESG group had a mean difference of excess weight loss of 44.7% (95% CI, 37.5%-51.9%) and a mean difference of total weight loss of 12.6% (95% CI, 10.7%-14.5%), compared with the control group at 52 weeks. At 52 weeks, 77% of the ESG group had at least a 25% excess weight loss, which was the secondary endpoint, compared with 12% of the control group (P < .0001).

Overall, 80% of the ESG group had an improvement in at least one metabolic comorbidity, while 12% experienced a worsening. Among the control group, 45% had an improvement and 50% worsened. Among 27 patients in the treatment group with diabetes, 93% experienced an improvement in hemoglobin A1c levels, compared with 15% of patients with diabetes in the control group. Similarly among patients with hypertension, 60% in the intervention group had an improvement, compared with 40% of controls. Of those with metabolic syndrome, 83% improved after undergoing surgery, compared with 35% of controls.

At 2 years, 68% of the ESG group who achieved a 25% EWL continued to have at least 25% EWL; 2% in the treatment group had a serious ESG-related adverse event, but there was no mortality or need for intensive care or follow-up surgery.
 

Aiming for level I evidence

“The results are very encouraging, so I think it’s good news for the field of bariatric endoscopy. I think it’s going to provide more confidence to patients and physicians, and for new trainees who are interested in this field, I think it’s going to inspire them,” said Shailendra Singh, MD, who was asked to comment on the study. Dr. Singh is an associate professor of medicine and director of bariatric medicine at West Virginia University, Morgantown.

The study could also improve insurance coverage of the procedure, said Dr. Singh. “I think this study will help us reach out to the payers and give them the data behind this because they always look for level I evidence. ESG is a relatively new endoscopic procedure; I think this is a step forward in that direction,” he said.

The study underlines the applicability of the procedure to patients who don’t want more invasive surgery, or who can’t tolerate some of the higher efficacy medications that are increasingly available.

It is also just one of various options for obesity treatment, which are increasingly being used in combination, according to Avlin Imaeda, MD. “Just like we see in hypertension, where you progressively add more and more medications, I think we’re going to see obesity treatment go that way too. I see this as adding choice for patients and adding to this potentially multimodal approach,” said Dr. Imaeda, an associate professor of medicine at Yale University, New Haven, Conn., who was not involved in the study.

The study authors report various financial relationships, including some with Apollo Endosurgery, which funded this study. Dr. Issa and Dr. Imaeda have no relevant financial disclosures. Dr. Singh is a consultant for Apollo Endosurgery.

This article was updated Aug. 18, 2022.

SAN DIEGO – Even after recovery of an acute COVID-19 infection, some patients experience extended or even long-term symptoms that can range from mild to debilitating. Some of these symptoms are neurological: headaches, brain fog, cognitive impairment, loss of taste or smell, and even cerebrovascular complications such stroke. There are even hints that COVID-19 infection could lead to future neurodegeneration.

Those issues have prompted efforts to identify biomarkers that can help track and monitor neurological complications of COVID-19. “Throughout the course of the pandemic, it has become apparent that COVID-19 can cause various neurological symptoms. Because of this, it’s really important for us to find a way to monitor and understand neurological complications occurring in patients with COVID 19,” Jennifer Cooper said during a lecture at the Alzheimer’s Association International Conference. She presented new research suggesting that neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) may prove useful.

Ms. Cooper is a master’s degree student at the University of British Columbia and Canada.
 

Looking for sensitivity and specificity in plasma biomarkers

The researchers turned to plasma-based markers because they can reflect underlying pathology in the central nervous system. They focused on NfL, which reflects axonal damage, and GFAP, which is a marker of astrocyte activation.

The researchers analyzed data from 209 patients with COVID-19 who were admitted to the Vancouver (B.C.) General Hospital intensive care unit. Sixty-four percent were male, and the median age was 61 years. Sixty percent were ventilated, and 17% died.

The researchers determined if an individual patient’s biomarker level at hospital admission fell within a normal biomarker reference interval. A total of 53% had NfL levels outside the normal range, and 42% had GFAP levels outside the normal range. In addition, 31% of patients had both GFAP and NfL levels outside of the normal range.

Among all patients, 12% experienced ischemia, 4% hemorrhage, 2% seizures, and 10% degeneration.

At admission, NfL predicted a neurological complication with an area under the curve (AUC) of 0.702. GFAP had an AUC of 0.722. In combination, they had an AUC of 0.743. At 1 week, NfL had an AUC of 0.802, GFAP an AUC of 0.733, and the combination an AUC of 0.812.

Using age-specific cutoff values, the researchers found increased risks for neurological complications at admission (NfL odds ratio [OR], 2.9; GFAP OR, 1.6; combined OR, 2.1) and at 1 week (NfL OR, not significant; GFAP OR, 4.8; combined OR, 6.6). “We can see that both NFL and GFAP have utility in detecting neurological complications. And combining both of our markers improves detection at both time points. NfL is a marker that provides more sensitivity, where in this cohort GFAP is a marker that provides a little bit more specificity,” said Ms. Cooper.
 

Will additional biomarkers help?

The researchers are continuing to follow up patients at 6 months and 18 months post diagnosis, using neuropsychiatric tests and additional biomarker analysis, as well as PET and MRI scans. The patient sample is being expanded to those in the general hospital ward and some who were not hospitalized.

During the Q&A session, Ms. Cooper was asked if the group had collected reference data from patients who were admitted to the ICU with non-COVID disease. She responded that the group has some of that data, but as the pandemic went on they had difficulty finding patients who had never been infected with COVID to serve as reliable controls. To date, they have identified 33 controls who had a respiratory condition when admitted to the ICU. “What we see is the neurological biomarker levels in COVID are slightly lower than those with another respiratory condition in the ICU. But the data has a massive spread and the significance is very small between the two groups,” said Ms. Cooper.
 

Unanswered questions

The study is interesting, but leaves a lot of unanswered questions, according to Wiesje van der Flier, PhD, who moderated the session where the study was presented. “There are a lot of unknowns still: Will [the biomarkers] become normal again, once the COVID is over? Also, there was an increased risk, but it was not a one-to-one correspondence, so you can also have the increased markers but not have the neurological signs or symptoms. So I thought there were lots of questions as well,” said Dr. van der Flier, professor of neurology at Amsterdam University Medical Center.

She noted that researchers at her institution in Amsterdam have observed similar relationships, and that the associations between neurological complications and plasma biomarkers over time will be an important topic of study.

The work could provide more information on neurological manifestations of long COVID, such as long-haul fatigue. “You might also think that’s some response in their brain. It would be great if we could actually capture that [using biomarkers],” said Dr. van der Flier.

Ms. Cooper and Dr. van der Flier have no relevant financial disclosures.

SAN DIEGO – Even after recovery of an acute COVID-19 infection, some patients experience extended or even long-term symptoms that can range from mild to debilitating. Some of these symptoms are neurological: headaches, brain fog, cognitive impairment, loss of taste or smell, and even cerebrovascular complications such stroke. There are even hints that COVID-19 infection could lead to future neurodegeneration.

Those issues have prompted efforts to identify biomarkers that can help track and monitor neurological complications of COVID-19. “Throughout the course of the pandemic, it has become apparent that COVID-19 can cause various neurological symptoms. Because of this, it’s really important for us to find a way to monitor and understand neurological complications occurring in patients with COVID 19,” Jennifer Cooper said during a lecture at the Alzheimer’s Association International Conference. She presented new research suggesting that neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) may prove useful.

Ms. Cooper is a master’s degree student at the University of British Columbia and Canada.
 

Looking for sensitivity and specificity in plasma biomarkers

The researchers turned to plasma-based markers because they can reflect underlying pathology in the central nervous system. They focused on NfL, which reflects axonal damage, and GFAP, which is a marker of astrocyte activation.

The researchers analyzed data from 209 patients with COVID-19 who were admitted to the Vancouver (B.C.) General Hospital intensive care unit. Sixty-four percent were male, and the median age was 61 years. Sixty percent were ventilated, and 17% died.

The researchers determined if an individual patient’s biomarker level at hospital admission fell within a normal biomarker reference interval. A total of 53% had NfL levels outside the normal range, and 42% had GFAP levels outside the normal range. In addition, 31% of patients had both GFAP and NfL levels outside of the normal range.

Among all patients, 12% experienced ischemia, 4% hemorrhage, 2% seizures, and 10% degeneration.

At admission, NfL predicted a neurological complication with an area under the curve (AUC) of 0.702. GFAP had an AUC of 0.722. In combination, they had an AUC of 0.743. At 1 week, NfL had an AUC of 0.802, GFAP an AUC of 0.733, and the combination an AUC of 0.812.

Using age-specific cutoff values, the researchers found increased risks for neurological complications at admission (NfL odds ratio [OR], 2.9; GFAP OR, 1.6; combined OR, 2.1) and at 1 week (NfL OR, not significant; GFAP OR, 4.8; combined OR, 6.6). “We can see that both NFL and GFAP have utility in detecting neurological complications. And combining both of our markers improves detection at both time points. NfL is a marker that provides more sensitivity, where in this cohort GFAP is a marker that provides a little bit more specificity,” said Ms. Cooper.
 

Will additional biomarkers help?

The researchers are continuing to follow up patients at 6 months and 18 months post diagnosis, using neuropsychiatric tests and additional biomarker analysis, as well as PET and MRI scans. The patient sample is being expanded to those in the general hospital ward and some who were not hospitalized.

During the Q&A session, Ms. Cooper was asked if the group had collected reference data from patients who were admitted to the ICU with non-COVID disease. She responded that the group has some of that data, but as the pandemic went on they had difficulty finding patients who had never been infected with COVID to serve as reliable controls. To date, they have identified 33 controls who had a respiratory condition when admitted to the ICU. “What we see is the neurological biomarker levels in COVID are slightly lower than those with another respiratory condition in the ICU. But the data has a massive spread and the significance is very small between the two groups,” said Ms. Cooper.
 

Unanswered questions

The study is interesting, but leaves a lot of unanswered questions, according to Wiesje van der Flier, PhD, who moderated the session where the study was presented. “There are a lot of unknowns still: Will [the biomarkers] become normal again, once the COVID is over? Also, there was an increased risk, but it was not a one-to-one correspondence, so you can also have the increased markers but not have the neurological signs or symptoms. So I thought there were lots of questions as well,” said Dr. van der Flier, professor of neurology at Amsterdam University Medical Center.

She noted that researchers at her institution in Amsterdam have observed similar relationships, and that the associations between neurological complications and plasma biomarkers over time will be an important topic of study.

The work could provide more information on neurological manifestations of long COVID, such as long-haul fatigue. “You might also think that’s some response in their brain. It would be great if we could actually capture that [using biomarkers],” said Dr. van der Flier.

Ms. Cooper and Dr. van der Flier have no relevant financial disclosures.

SAN DIEGO – Even after recovery of an acute COVID-19 infection, some patients experience extended or even long-term symptoms that can range from mild to debilitating. Some of these symptoms are neurological: headaches, brain fog, cognitive impairment, loss of taste or smell, and even cerebrovascular complications such stroke. There are even hints that COVID-19 infection could lead to future neurodegeneration.

Those issues have prompted efforts to identify biomarkers that can help track and monitor neurological complications of COVID-19. “Throughout the course of the pandemic, it has become apparent that COVID-19 can cause various neurological symptoms. Because of this, it’s really important for us to find a way to monitor and understand neurological complications occurring in patients with COVID 19,” Jennifer Cooper said during a lecture at the Alzheimer’s Association International Conference. She presented new research suggesting that neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) may prove useful.

Ms. Cooper is a master’s degree student at the University of British Columbia and Canada.
 

Looking for sensitivity and specificity in plasma biomarkers

The researchers turned to plasma-based markers because they can reflect underlying pathology in the central nervous system. They focused on NfL, which reflects axonal damage, and GFAP, which is a marker of astrocyte activation.

The researchers analyzed data from 209 patients with COVID-19 who were admitted to the Vancouver (B.C.) General Hospital intensive care unit. Sixty-four percent were male, and the median age was 61 years. Sixty percent were ventilated, and 17% died.

The researchers determined if an individual patient’s biomarker level at hospital admission fell within a normal biomarker reference interval. A total of 53% had NfL levels outside the normal range, and 42% had GFAP levels outside the normal range. In addition, 31% of patients had both GFAP and NfL levels outside of the normal range.

Among all patients, 12% experienced ischemia, 4% hemorrhage, 2% seizures, and 10% degeneration.

At admission, NfL predicted a neurological complication with an area under the curve (AUC) of 0.702. GFAP had an AUC of 0.722. In combination, they had an AUC of 0.743. At 1 week, NfL had an AUC of 0.802, GFAP an AUC of 0.733, and the combination an AUC of 0.812.

Using age-specific cutoff values, the researchers found increased risks for neurological complications at admission (NfL odds ratio [OR], 2.9; GFAP OR, 1.6; combined OR, 2.1) and at 1 week (NfL OR, not significant; GFAP OR, 4.8; combined OR, 6.6). “We can see that both NFL and GFAP have utility in detecting neurological complications. And combining both of our markers improves detection at both time points. NfL is a marker that provides more sensitivity, where in this cohort GFAP is a marker that provides a little bit more specificity,” said Ms. Cooper.
 

Will additional biomarkers help?

The researchers are continuing to follow up patients at 6 months and 18 months post diagnosis, using neuropsychiatric tests and additional biomarker analysis, as well as PET and MRI scans. The patient sample is being expanded to those in the general hospital ward and some who were not hospitalized.

During the Q&A session, Ms. Cooper was asked if the group had collected reference data from patients who were admitted to the ICU with non-COVID disease. She responded that the group has some of that data, but as the pandemic went on they had difficulty finding patients who had never been infected with COVID to serve as reliable controls. To date, they have identified 33 controls who had a respiratory condition when admitted to the ICU. “What we see is the neurological biomarker levels in COVID are slightly lower than those with another respiratory condition in the ICU. But the data has a massive spread and the significance is very small between the two groups,” said Ms. Cooper.
 

Unanswered questions

The study is interesting, but leaves a lot of unanswered questions, according to Wiesje van der Flier, PhD, who moderated the session where the study was presented. “There are a lot of unknowns still: Will [the biomarkers] become normal again, once the COVID is over? Also, there was an increased risk, but it was not a one-to-one correspondence, so you can also have the increased markers but not have the neurological signs or symptoms. So I thought there were lots of questions as well,” said Dr. van der Flier, professor of neurology at Amsterdam University Medical Center.

She noted that researchers at her institution in Amsterdam have observed similar relationships, and that the associations between neurological complications and plasma biomarkers over time will be an important topic of study.

The work could provide more information on neurological manifestations of long COVID, such as long-haul fatigue. “You might also think that’s some response in their brain. It would be great if we could actually capture that [using biomarkers],” said Dr. van der Flier.

Ms. Cooper and Dr. van der Flier have no relevant financial disclosures.

SAN DIEGO – Among older patients with mild cognitive impairment (MCI), the combination of vitamin D and physical exercise plus cognitive training led to greater improvements than exercise alone. The findings were drawn from an unusual study design that split patients into five groups, one of which included both interventions.

After the study was completed, researchers collapsed the groups into a single analysis to compare the different regimens, according to Manuel Montero-Odasso, MD, PhD, who presented the work at the Alzheimer’s Association International Conference. He is a geriatrician at Parkwood Institute, London, Ont.

Two previous trials looked at whether the combination of exercise plus cognitive training could outperform either intervention alone. In both, the combination improved cognition but not as much as either intervention alone. “So it seemed that when they combine it, they didn’t do as well,” said Dr. Montero-Odasso. Those findings left doubt about whether or not there is synergism between the two approaches.
 

Sequential, not simultaneous

A possible explanation for the finding is that patients who are doing both cognitive training and physical exercise simultaneously might not be able to focus enough on either task to do get the maximum benefit. “When we try to combine concurrently, participants or patients cannot focus and do enough progression in both at the same time. That’s the reason we designed the trial in a way that the interventions were sequential. You got a very good quality (cognitive) training, and later you got the exercise,” said Dr. Montero-Odasso.

In the new study, patients receiving both interventions conducted the cognitive training first, then did physical exercises 30 minutes later. “The practical message is that you should follow a program. Something I see in my patients, when they do the two things at the same time, they don’t pay enough attention,” said Dr. Montero-Odasso.

The researchers added vitamin D to the regimen as there have been small studies reporting that vitamin D supplementation can lead to greater muscle mass resulting from exercise.

The study included 176 patients aged 60-85 with MCI. The researchers excluded patients already participating in an active exercise program with a personal trainer, as well as those taking vitamin D at doses higher than 1,000 IU/day.

Over 20 weeks, the randomized groups included combination exercise and cognitive training with vitamin D (10,000 IU three times per week), exercise and cognitive training with placebo, exercise with a cognitive control and vitamin D, exercise with a cognitive control and placebo, and an exercise control (balance and toning) with cognitive control and placebo.

The interventions were completed three times per week. Cognitive training employed a tablet with multifunctional tasks and memory components. It was adaptive, becoming more difficult as patients improved or simplifying the task if a patient struggled. The exercise component included 40 minutes of progressive, supervised resistance training, followed by 20 minutes of aerobic exercise.

Compared with the double-placebo group, the double-intervention group had significant improvement in cognitive performance. “Exercise alone without cognitive training shows an effect, but that effect was lower than a combination with cognitive training,” said Dr. Montero-Odasso.

The combined groups had medium effect sizes on cognition when combined with vitamin D (Cohen’s d, 0.65; P = .003) and with vitamin D placebo (Cohen’s d, 0.58; P = .013). There were nonsignificant improvements in the exercise and vitamin D group (Cohen’s d, 0.30; P = .241) and the exercise plus placebo group (Cohen’s d, 0.42; P = .139)

After collapsing the arms, the researchers found that the exercise plus cognitive training regimen had an effect size of 0.62 (P = .002), while exercise alone only trended toward improvement and with a small effect size (Cohen’s d, 0.36; P = .13). There was no apparent effect of vitamin D supplementation, though Dr. Montero-Odasso pointed out that most participants were taking vitamin D supplements before study entry and had normal to high serum levels of vitamin D.
 

‘Optimistic’ results

The study was limited by an inability to retain patients due to the COVID-19 pandemic, leading to a dropout rate of 17%.

“I think the idea of combining risk reduction strategies together in a population and individuals with MCI is really exciting. These are optimistic results. You certainly need to look into a larger and more diverse population as it goes forward,” said Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, who was asked to comment on the study.

She noted that the study looked at all-cause cognitive impairment. It would be interesting, Dr. Snyder said, to see how individuals with different underlying conditions handle the combination intervention.

The researchers are now in the planning stage of the Synergic 2 trial, which will incorporate exercise and cognitive training, plus diet and sleep counseling. It will be conducted virtually, involving one-to-one interactions with coaches.

Dr. Montero-Odasso and Dr. Snyder have no relevant financial disclosures.

SAN DIEGO – Among older patients with mild cognitive impairment (MCI), the combination of vitamin D and physical exercise plus cognitive training led to greater improvements than exercise alone. The findings were drawn from an unusual study design that split patients into five groups, one of which included both interventions.

After the study was completed, researchers collapsed the groups into a single analysis to compare the different regimens, according to Manuel Montero-Odasso, MD, PhD, who presented the work at the Alzheimer’s Association International Conference. He is a geriatrician at Parkwood Institute, London, Ont.

Two previous trials looked at whether the combination of exercise plus cognitive training could outperform either intervention alone. In both, the combination improved cognition but not as much as either intervention alone. “So it seemed that when they combine it, they didn’t do as well,” said Dr. Montero-Odasso. Those findings left doubt about whether or not there is synergism between the two approaches.
 

Sequential, not simultaneous

A possible explanation for the finding is that patients who are doing both cognitive training and physical exercise simultaneously might not be able to focus enough on either task to do get the maximum benefit. “When we try to combine concurrently, participants or patients cannot focus and do enough progression in both at the same time. That’s the reason we designed the trial in a way that the interventions were sequential. You got a very good quality (cognitive) training, and later you got the exercise,” said Dr. Montero-Odasso.

In the new study, patients receiving both interventions conducted the cognitive training first, then did physical exercises 30 minutes later. “The practical message is that you should follow a program. Something I see in my patients, when they do the two things at the same time, they don’t pay enough attention,” said Dr. Montero-Odasso.

The researchers added vitamin D to the regimen as there have been small studies reporting that vitamin D supplementation can lead to greater muscle mass resulting from exercise.

The study included 176 patients aged 60-85 with MCI. The researchers excluded patients already participating in an active exercise program with a personal trainer, as well as those taking vitamin D at doses higher than 1,000 IU/day.

Over 20 weeks, the randomized groups included combination exercise and cognitive training with vitamin D (10,000 IU three times per week), exercise and cognitive training with placebo, exercise with a cognitive control and vitamin D, exercise with a cognitive control and placebo, and an exercise control (balance and toning) with cognitive control and placebo.

The interventions were completed three times per week. Cognitive training employed a tablet with multifunctional tasks and memory components. It was adaptive, becoming more difficult as patients improved or simplifying the task if a patient struggled. The exercise component included 40 minutes of progressive, supervised resistance training, followed by 20 minutes of aerobic exercise.

Compared with the double-placebo group, the double-intervention group had significant improvement in cognitive performance. “Exercise alone without cognitive training shows an effect, but that effect was lower than a combination with cognitive training,” said Dr. Montero-Odasso.

The combined groups had medium effect sizes on cognition when combined with vitamin D (Cohen’s d, 0.65; P = .003) and with vitamin D placebo (Cohen’s d, 0.58; P = .013). There were nonsignificant improvements in the exercise and vitamin D group (Cohen’s d, 0.30; P = .241) and the exercise plus placebo group (Cohen’s d, 0.42; P = .139)

After collapsing the arms, the researchers found that the exercise plus cognitive training regimen had an effect size of 0.62 (P = .002), while exercise alone only trended toward improvement and with a small effect size (Cohen’s d, 0.36; P = .13). There was no apparent effect of vitamin D supplementation, though Dr. Montero-Odasso pointed out that most participants were taking vitamin D supplements before study entry and had normal to high serum levels of vitamin D.
 

‘Optimistic’ results

The study was limited by an inability to retain patients due to the COVID-19 pandemic, leading to a dropout rate of 17%.

“I think the idea of combining risk reduction strategies together in a population and individuals with MCI is really exciting. These are optimistic results. You certainly need to look into a larger and more diverse population as it goes forward,” said Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, who was asked to comment on the study.

She noted that the study looked at all-cause cognitive impairment. It would be interesting, Dr. Snyder said, to see how individuals with different underlying conditions handle the combination intervention.

The researchers are now in the planning stage of the Synergic 2 trial, which will incorporate exercise and cognitive training, plus diet and sleep counseling. It will be conducted virtually, involving one-to-one interactions with coaches.

Dr. Montero-Odasso and Dr. Snyder have no relevant financial disclosures.

SAN DIEGO – Among older patients with mild cognitive impairment (MCI), the combination of vitamin D and physical exercise plus cognitive training led to greater improvements than exercise alone. The findings were drawn from an unusual study design that split patients into five groups, one of which included both interventions.

After the study was completed, researchers collapsed the groups into a single analysis to compare the different regimens, according to Manuel Montero-Odasso, MD, PhD, who presented the work at the Alzheimer’s Association International Conference. He is a geriatrician at Parkwood Institute, London, Ont.

Two previous trials looked at whether the combination of exercise plus cognitive training could outperform either intervention alone. In both, the combination improved cognition but not as much as either intervention alone. “So it seemed that when they combine it, they didn’t do as well,” said Dr. Montero-Odasso. Those findings left doubt about whether or not there is synergism between the two approaches.
 

Sequential, not simultaneous

A possible explanation for the finding is that patients who are doing both cognitive training and physical exercise simultaneously might not be able to focus enough on either task to do get the maximum benefit. “When we try to combine concurrently, participants or patients cannot focus and do enough progression in both at the same time. That’s the reason we designed the trial in a way that the interventions were sequential. You got a very good quality (cognitive) training, and later you got the exercise,” said Dr. Montero-Odasso.

In the new study, patients receiving both interventions conducted the cognitive training first, then did physical exercises 30 minutes later. “The practical message is that you should follow a program. Something I see in my patients, when they do the two things at the same time, they don’t pay enough attention,” said Dr. Montero-Odasso.

The researchers added vitamin D to the regimen as there have been small studies reporting that vitamin D supplementation can lead to greater muscle mass resulting from exercise.

The study included 176 patients aged 60-85 with MCI. The researchers excluded patients already participating in an active exercise program with a personal trainer, as well as those taking vitamin D at doses higher than 1,000 IU/day.

Over 20 weeks, the randomized groups included combination exercise and cognitive training with vitamin D (10,000 IU three times per week), exercise and cognitive training with placebo, exercise with a cognitive control and vitamin D, exercise with a cognitive control and placebo, and an exercise control (balance and toning) with cognitive control and placebo.

The interventions were completed three times per week. Cognitive training employed a tablet with multifunctional tasks and memory components. It was adaptive, becoming more difficult as patients improved or simplifying the task if a patient struggled. The exercise component included 40 minutes of progressive, supervised resistance training, followed by 20 minutes of aerobic exercise.

Compared with the double-placebo group, the double-intervention group had significant improvement in cognitive performance. “Exercise alone without cognitive training shows an effect, but that effect was lower than a combination with cognitive training,” said Dr. Montero-Odasso.

The combined groups had medium effect sizes on cognition when combined with vitamin D (Cohen’s d, 0.65; P = .003) and with vitamin D placebo (Cohen’s d, 0.58; P = .013). There were nonsignificant improvements in the exercise and vitamin D group (Cohen’s d, 0.30; P = .241) and the exercise plus placebo group (Cohen’s d, 0.42; P = .139)

After collapsing the arms, the researchers found that the exercise plus cognitive training regimen had an effect size of 0.62 (P = .002), while exercise alone only trended toward improvement and with a small effect size (Cohen’s d, 0.36; P = .13). There was no apparent effect of vitamin D supplementation, though Dr. Montero-Odasso pointed out that most participants were taking vitamin D supplements before study entry and had normal to high serum levels of vitamin D.
 

‘Optimistic’ results

The study was limited by an inability to retain patients due to the COVID-19 pandemic, leading to a dropout rate of 17%.

“I think the idea of combining risk reduction strategies together in a population and individuals with MCI is really exciting. These are optimistic results. You certainly need to look into a larger and more diverse population as it goes forward,” said Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, who was asked to comment on the study.

She noted that the study looked at all-cause cognitive impairment. It would be interesting, Dr. Snyder said, to see how individuals with different underlying conditions handle the combination intervention.

The researchers are now in the planning stage of the Synergic 2 trial, which will incorporate exercise and cognitive training, plus diet and sleep counseling. It will be conducted virtually, involving one-to-one interactions with coaches.

Dr. Montero-Odasso and Dr. Snyder have no relevant financial disclosures.

Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.

Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.

A new pilot study showed that a telehealth intervention focusing on individualized treatment and environmental cues can be delivered to patients and caregivers in a rural environment.

The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.

Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
 

Caregiving hacks

The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.

For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.

An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.

“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.

In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
 

Impactful care

The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.

“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
 

Empowering caregivers

The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).

“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.

The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.

Dr. Rhodus and Ms. Gross have no relevant financial disclosures.

Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.

Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.

A new pilot study showed that a telehealth intervention focusing on individualized treatment and environmental cues can be delivered to patients and caregivers in a rural environment.

The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.

Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
 

Caregiving hacks

The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.

For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.

An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.

“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.

In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
 

Impactful care

The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.

“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
 

Empowering caregivers

The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).

“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.

The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.

Dr. Rhodus and Ms. Gross have no relevant financial disclosures.

Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.

Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.

A new pilot study showed that a telehealth intervention focusing on individualized treatment and environmental cues can be delivered to patients and caregivers in a rural environment.

The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.

Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
 

Caregiving hacks

The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.

For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.

An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.

“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.

In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
 

Impactful care

The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.

“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
 

Empowering caregivers

The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).

“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.

The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.

Dr. Rhodus and Ms. Gross have no relevant financial disclosures.

It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality. New evidence shows that the experience of racism is associated with worse cognitive function in later life.

That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.

“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
 

Racism, memory, and cognition in middle-aged patients

Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.

“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.

Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).

The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.

The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.

“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.

The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
 

Latinx concerns

Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.

She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
 

Racism and cognition in the elderly

At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.

The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.

The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.

Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.

Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.

It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality. New evidence shows that the experience of racism is associated with worse cognitive function in later life.

That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.

“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
 

Racism, memory, and cognition in middle-aged patients

Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.

“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.

Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).

The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.

The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.

“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.

The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
 

Latinx concerns

Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.

She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
 

Racism and cognition in the elderly

At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.

The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.

The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.

Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.

Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.

It is generally understood that racism, whether structural or personal, harms the well-being of the individual who experiences it. It has harmful health effects, and it contributes to ethnic inequality. New evidence shows that the experience of racism is associated with worse cognitive function in later life.

That was the fundamental message behind two studies presented at a press conference at the Alzheimer’s Association International Conference.

“We know that there are communities like black African Americans and Hispanic Latinos who are at greater risk for developing Alzheimer’s or another dementia,” said Carl Hill, PhD, who served as a moderator during the press conference. He pointed out that the genetic and lifestyle factors linked to dementia tell only part of the story. “It’s important that the science also examines the unique experiences of those at greater risk for dementia in our society,” said Dr. Hill, who is Alzheimer’s Association Chief Diversity Equity and Inclusion Officer.
 

Racism, memory, and cognition in middle-aged patients

Jennifer J. Manly, PhD, professor of neuropsychology at Columbia University, New York, presented a study of experience of racism and memory scores among a highly diverse, middle-aged cohort.

“There’s little understanding of how the multiple levels of racism – including intrapersonal, institutional, and structural racism – influence cognitive aging and dementia risk,” Dr. Manly said during the press conference.

Among 1,095 participants, 19.5% were non-Latinx White (61% female, mean age 57), 26.0% were non-Latinx Black (63% female, mean age 56), 32.3% were English-speaking Latinx (66% female, mean age 50), and 21.2% were Spanish-speaking Latinx (68% female, mean age 58).

The researchers used the Everyday Discrimination (ED) scale to measure experience of individual racism, the Major Discrimination (MD) scale to measure experience of institutional racism, and residential segregation of the census block group for an individual’s parents to measure residential segregation. Outcome measures included the Digit Span to assess attention and working memory, and the Selective Reminding Test to assess episodic memory.

The study found a clear association between racism and cognition. “The association of interpersonal racism to memory corresponds to 3 years of chronological age, and was driven by non-Hispanic black participants. Next, there was a reliable relationship between institutional racism and memory scores among non-Hispanic black participants, such that each reported civil rights violation corresponded to the effect of about 4.5 years of age on memory,” said Dr. Manly.

“The bottom line is that our results suggest that exposure to racism is a substantial driver of later life memory function, even in middle age, and especially for Black people,” Dr. Manly added.

The results should alert physicians to the complexities of racism and its impact. “Health providers need to be aware that many accumulated risks are historical and structural, and not controlled by the individual. Maybe more importantly, the medical system itself may perpetuate discriminatory experiences that contribute to worse health,” said Dr. Manly.
 

Latinx concerns

Also at the press conference, Adriana Perez, PhD, emphasized the challenges that Spanish-speaking Latinxs have with health care. Just 5%-7% of nurses are Latinx. “The same could be said for physicians, for clinical psychologists ... as you look at the really critical positions to address brain health equity, we are not represented there,” said Dr. Perez, an assistant professor and senior fellow at the University of Pennsylvania School of Nursing in Philadelphia.

She also pointed out that Latinx representation in clinical trials is very low, even though surveys performed by the Alzheimer’s Association show that this population values medical science and is willing to participate. In fact, 85% said they would participate if invited. The trouble is that many clinical trial announcements state that participants must speak English. Even the many Latinos who are bilingual may be put off by that wording: “That is a message that you’re not invited. That’s how it’s perceived,” said Dr. Perez.
 

Racism and cognition in the elderly

At the press conference, Kristen George, PhD, presented results from a study of individuals over age 90. “Racial disparities in dementia have been well characterized, particularly among those people who are aged 65 and older, but we don’t know very much about the oldest old individuals who are aged 90 and older. This group is one of the fastest growing segments of the population, and it’s becoming increasingly diverse,” said Dr. George, assistant professor of epidemiology at the University of California, Davis.

The group enrolled 445 Asian, Black, Latinx, White, and multiracial individuals who were members of Kaiser Permanente Northern California, with a mean age of 92.7 years. They used the Major Experiences of Discrimination Scale to assess discrimination.

The researchers divided them into three groups based on gender, race, and responses to the 10-item scale. Class 1 included largely White men who had reported workplace discrimination, with an average of two major discrimination experiences. Class 2 was made up of White women and non-Whites who reported little or no discrimination, with an average of 0 experiences. Class 3 included all non-White participants, and they reported a mean of four discrimination experiences.

Using class 2 as a reference, executive function was better among class 1 individuals (beta = 0.28; 95% CI, 0.03-0.52) but there was no significant difference between class 3 and class 2. Class 1 had better baseline semantic memory than class 2 (beta = 0.33; 95% CI, 0.07-0.58), and those in class 3 performed significantly worse than class 2 (beta = –0.24; 95% CI, –0.48 to –0.00). There were no between-group differences in baseline verbal or episodic memory.

Dr. Perez, Dr. Manly, Dr. George, and Dr. Hill have no relevant financial disclosures.