American Neuropsychiatric Association (ANPA): Annual Meeting

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER - Apathy symptoms in nondemented Parkinson’s disease patients selectively impede executive function tasks while sparing other cognitive domains, including working memory, recent memory, language, and processing speed.

Moreover, apathy specifically affects those executive function tasks that are associated with mesial frontal and anterior cingulate cortex circuitry, rather than dorsolateral prefrontal systems, Lindsey Kirsch-Darrow, Ph.D., said at the annual meeting of the American Neuropsychiatric Association.

The neuropsychiatric comorbidities of depression, anxiety, and apathy are highly prevalent among Parkinson’s disease patients. Of these, apathy (lack of motivation) is far and away the least understood, and the one on which Dr. Kirsch-Darrow’s research has focused.

Apathy in Parkinson’s disease is an important issue because – as in many neurologic diseases – apathy has been associated with a less-robust functional outcome and increased caregiver distress, noted Dr. Kirsch-Darrow, a postdoctoral fellow at Johns Hopkins University, Baltimore.

In her new study of 161 nondemented subjects with idiopathic Parkinson’s disease in the middle stages of motor disease, 17.4% had apathy without depression, 9.3% had depression without apathy, and 16% had both, as defined by the 14-item Apathy Scale and the Beck Depression Inventory. This is consistent with other studies showing that apathy in Parkinson’s disease is distinct from depression.

It is also known that apathy is related to dementia and impaired cognitive functioning in Parkinson’s disease patients. In an analysis involving 233 Parkinson’s disease patients, the prevalence of apathy was 36% in those who were nondemented, 51% in an unselected sample of Parkinson’s disease patients, and 80% in demented ones. But because of potential confounders in this and other studies, it was unclear if apathy symptoms independently contribute to cognitive status in nondemented patients. That’s what Dr. Kirsch-Darrow set out to learn in her study of 161 nondemented Parkinson’s disease patients, all of whom completed a roughly 3-hour neurocognitive battery as well as mood measures.

She found that the more apathetic the patient, the greater the impairment of executive function. And in an analysis incorporating patient demographics, disease variables, depression, apathy, and anxiety, apathy was the sole variable that contributed to variance in executive function.

Apathy’s effect on executive function was highly selective. The higher a patient’s Apathy Scale score, the worse the performance on the Stroop Color and Word Test, which tests cognitive interference. Tests of other executive function domains (including letter fluency, animal fluency, Wisconsin Card Sorting, and the Trailmaking Test Part B) were unrelated to apathy scores. None of the other examined variables (including depression, demographics, and anxiety) contributed to the variance in Stroop scores.

Important questions to be addressed in future research include whether apathy is simply a marker for Parkinson’s disease progression, and whether apathy in Parkinson’s disease predicts later cognitive decline. One French study found that more apathetic than nonapathetic patients converted to dementia over 18 months of follow-up (Mov. Disord. 2009;24:2391-7), but this needs replication because of confounding issues, according to Dr. Kirsch-Darrow.

She observed that little research has been done on the treatment of parkinsonian apathy.

"Antidepressants typically don’t help. In fact, a study that’s ongoing in our laboratory right now suggests that SSRIs may actually worsen parkinsonian apathy; SNRIs [serotonin norepinephrine reuptake inhibitors] did not," she said.

A recent study showed that apathy in Parkinson’s disease patients improved with transcranial magnetic stimulation, but sham therapy brought an equal improvement. It may be that the behavioral activation resulting simply from having a patient come to the clinic and interact with staff is helpful. This implies a potential future role for cognitive behavioral therapy, Dr. Kirsch-Darrow said.

She conducted her study on apathy’s unique contribution to executive function in Parkinson’s disease while she was a graduate student at the University of Florida. Her research is funded by the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation for Parkinson’s Research, and the American Neuropsychiatric Association. She declared having no relevant financial interests.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER – The presence of depression, apathy, or agitation in patients who have mild cognitive impairment signals an increased risk of progression to dementia within the next several years, according to a large prospective cohort study.

These neuropsychiatric symptoms may provide a clinically useful alternative to the costly brain imaging studies and cerebrospinal fluid (CSF) biomarkers now being developed as predictors of progression from mild cognitive impairment (MCI) to dementia, Dr. Yonas Geda said at the annual meeting of the American Neuropsychiatric Association.

He reported on 275 patients aged 70-89 years with baseline MCI diagnosed using standard published criteria. They were prospectively followed for a median 2.8 years as part of the Mayo Clinic Study of Aging. The participants, roughly equally split between men and women, were independently assessed for progression to dementia by neurologist evaluation, nursing assessment, and psychometric testing using the Neuropsychiatric Inventory Questionnaire. An expert panel evaluated all three data streams in order to diagnose dementia.

At baseline, 49 patients with MCI had apathy and 226 did not. During follow-up, 43% of those with apathy developed dementia, as did 26% of patients with MCI but not apathy. Upon adjustment for age, sex, education, and Charlson Comorbidity Index score, individuals with MCI and apathy were 2.1 times more likely to progress to dementia than were those with MCI and no apathy, reported Dr. Geda of the Mayo Clinic, Rochester, Minn.

Seventy-one patients had MCI and depression at enrollment. They had a 40% rate of progression to dementia during follow-up, compared with 25% in those with MCI but no depression. This translated to an adjusted 1.6-fold increased risk.

Of the 26 participants with MCI and agitation, 54% progressed to dementia, as did 26% of nonagitated patients with MCI, for a 2.7-fold increased risk.

Dr. Geda said he and his coinvestigators had anticipated that comorbid depression would be the biggest driver of progression from MCI to dementia. To their surprise, apathy and agitation turned out to be stronger predictors, although all three neuropsychiatric symptoms were independently associated with significantly increased risk. The higher risk of incident dementia associated with the neuropsychiatric symptoms became apparent early on in the follow-up period.

He declared having no relevant financial disclosures.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER - Intermittent theta burst stimulation of the cerebellar vermis in patients with refractory schizophrenia is a safe, noninvasive therapy that resulted in significantly improved negative symptoms, cognition, and mood in a proof-of-concept study.

The results of this small pilot study are potentially important, because current treatments for the negative symptoms of schizophrenia are so inadequate, Dr. Asli Demirtas-Tatlidede observed in presenting the study results at the annual meeting of the American Neuropsychiatric Association.

Theta burst stimulation (TBS) is a newer form of transcranial magnetic stimulation that modulates the activity of the dysfunctional cerebrocerebellar neural circuits that are present in schizophrenia in a shorter period of time, and with more potent and longer-lasting effects. TBS can be viewed as a noninvasive analogue to stimulation via implanted electrodes, a treatment that has shown efficacy for epilepsy, schizophrenia, and uncontrollable aggression, explained Dr. Demirtas-Tatlidede of Harvard Medical School, Boston.

She reported on eight patients with treatment-refractory schizophrenia, all right handed, who spent a week at the clinical research center at Beth Israel Deaconess Medical Center in Boston, where they underwent close monitoring as they received 10 sessions of TBS.

The TBS was administered twice daily on 5 consecutive days. Brain MRI and stereotactic localization were employed in order to direct the TBS to the cerebellar vermis. Psychiatric evaluations and comprehensive neuropsychological testing were done before and after TBS, and again 1 week after the final session.

The safety results were completely reassuring. There were no instances of cognitive decline, seizures, psychiatric or neuropsychological worsening, or any serious adverse events. Side effects were limited to brief, mild occipital headaches and small decreases in diastolic blood pressure lasting fewer than 5 minutes post TBS, both deemed probably treatment related.

In terms of efficacy end points, patients showed significant improvement in the PANSS (Positive and Negative Symptom Scale) negative subscale, with a mean 19% reduction from baseline. Participants also showed a significant improvement in mood as reflected in scores on the Calgary Depression Scale for Schizophrenics, as well as on self-reported visual analog scales for happiness and sadness.

Neuropsychological testing showed significantly fewer omissions in the working memory and interference conditions of the CPT (Continuous Performance Test). Patients also demonstrated a longer spatial span and better delay organization on the ROCF (Rey-Osterrieth Complex Figure) test during follow-up.

It has become apparent only quite recently that the limbic cerebellum – that is, the cerebellar vermis and fastigial nucleus – is closely involved in the regulation of affect and emotion. These structures are connected with the amygdala, hippocampus, hypothalamus, periaqueductal gray matter, and the limbic regions of the frontal and temporal lobes. The mechanism by which TBS brings improvement in negative symptoms, mood, and cognition remains unclear, but it is plausible that by stimulating the vermis, the treatment activates a dysfunctional cerebellum, enabling it to perform its normal function of correcting errors in thought and emotion, she continued.

The TBS was applied at 100% of active motor threshold intensity.

In response to an audience question as to whether these patients with treatment-refractory schizophrenia liked TBS therapy, Dr. Demirtas-Tatlidede’s senior co-investigator Dr. Jeremy D. Schmahmann replied that this was definitely the case. Indeed, one patient refused to accept that the study was over and has insisted on returning for TBS at monthly intervals.

"Her life has turned around. This is anecdotal, of course, but it’s extremely impressive," commented Dr. Schmahmann, professor of neurology at Harvard, and director of the ataxia unit and of the laboratory of neuroanatomy and cerebellar neurobiology at Massachusetts General Hospital.

Planning is underway for larger randomized, controlled studies incorporating a sham-stimulation control arm.

The pilot study was funded by the National Center for Research Resources, the National Institutes of Health, and several charitable foundations. Dr. Demirtas-Tatlidede and Dr. Schmahmann declared having no financial conflicts.

DENVER – Acquired sociopathy resulting from dementia is a common condition with two broad forms that require very different treatment strategies.

Demented patients who commit impulsive, sociopathic acts without emotion or concern for the consequences most often display frontal-caudate disturbances on functional neuroimaging. Their impulsive acts – for example, pathological stealing or disinhibited sexual behavior – tend to be nonviolent, Dr. Mario F. Mendez explained at the annual meeting of the American Neuropsychiatric Association.

In contrast, demented patients whose functional neuroimaging studies show more prominent temporal and parieto-occipital pathology are more likely to come to legal attention because of their nonimpulsive sociopathic acts, which are often violent in nature, said Dr. Mendez, professor of neurology and psychiatry and biobehavioral sciences at the University of California, Los Angeles.

Mechanistically, sociopathy in dementia results either from disinhibition secondary to frontal-predominant disease (such as vascular dementia, Huntington’s disease, or frontotemporal dementia), or from agitation and paranoia with memory and language impairment leading to misinterpretation of benign environmental cues as being hostile. Individuals with the nonimpulsive form tend to have advanced Alzheimer’s disease.

The hallmark of the impulsive form of sociopathy in dementia is lesions of the ventromedial prefrontal cortex, often with an additional contribution from the anterior temporolimbic area.

"Changes to the adjacent orbital frontal cortex region may be critical, resulting in impaired control of impulsive responses to tempting situations. Affected patients have impaired automatic feedback from social cues, especially angry or aversive expressions," according to Dr. Mendez, who is also director of the neurobehavior unit at the VA Greater Los Angeles Healthcare System.

As in psychopathy, sociopathy in dementia can take the form of goal-oriented aggression. But psychopathy differs from sociopathy in dementia in several key ways: Psychopathy first appears as antisocial behavior in childhood. And it is distinguished by additional features that are not found in sociopathy in dementia, including manipulation, callousness, grandiosity, sensation seeking, and deception.

To highlight the two broad types of sociopathy in dementia, Dr. Mendez presented his observational study of 33 affected patients. All of them had become involved with the legal system as a result of their behavior. In all, 22 were tagged for impulsive sociopathic acts and 11 for nonimpulsive acts.

The most common diagnoses among the 33 demented patients were Alzheimer’s disease, frontotemporal dementia, and vascular dementia or anoxic encephalopathy. Collectively, they accounted for 20 cases. But sociopathy has also been seen in association with many other brain diseases as well, including epilepsy, Parkinsonian syndromes, stroke, traumatic brain injury, and subarachnoid hemorrhage, Dr. Mendez said.

The 11 nonimpulsive patients were significantly older (mean age, 74 years), compared with age 62 for the impulsive group. The nonimpulsive group was also more impaired in language and/or cognition as reflected by their mean Mini-Mental State Exam score of 19.72, compared with 24.12 in the impulsive group.

On the Neuropsychiatric Inventory, the nonimpulsive patients scored higher on agitation, aggression, delusions, irritability, and depression. They demonstrated more impairment of language on the Category Fluency Test and the Mini-Boston Naming Test, performed worse on three-dimensional construction tasks, and their CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) scores also showed greater memory impairment.

Pathological stealing of unneeded items was common among the impulsive group. Unlike kleptomania, however, there is no increasing tension before these acts of pathological stealing, and no release of tension afterward. Inappropriate sexual behavior in the impulsive group included prolonged staring, indecent exposure, and unsolicited sexual approach.

Physical assaults were largely confined to the nonimpulsive group. "More severe memory/language deficits may lead to misinterpretations, paranoia, and suspicion. These patients can have paramnesic delusions, such as delusions of theft. They don’t remember where they left things and conclude malevolent intent. That’s very common in midstage Alzheimer’s disease," Dr. Mendez said.

In the impulsive sociopathy group, 82% of patients had disproportionate frontal-caudate abnormalities on functional neuroimaging, compared with 36% in the nonimpulsive group.

Drug treatment should target the mechanism underlying the sociopathic behavior, he said. For disinhibited impulsive patients, he and his UCLA colleagues often will titrate an SSRI up to the equivalent of 200 mg/day of sertraline. He has also been highly impressed with the effects of lamotrigine (Lamictal). In addition, he has successfully targeted disinhibition using valproic acid, divalproex, or propranolol.

Trazodone (Oleptro) Dr. Mendez’s first-line agent when the underlying mechanism of sociopathy in dementia is agitation and/or paranoia. But if trazodone proves ineffective, he doesn’t hesitate to move to the newer antipsychotic drugs, despite the black box warnings.

"To me, the most effective drug for delusional beliefs in, say, Alzheimer’s disease has been low-dose risperidone," Dr. Mendez said.

He declared having no relevant financial interests.

DENVER – Acquired sociopathy resulting from dementia is a common condition with two broad forms that require very different treatment strategies.

Demented patients who commit impulsive, sociopathic acts without emotion or concern for the consequences most often display frontal-caudate disturbances on functional neuroimaging. Their impulsive acts – for example, pathological stealing or disinhibited sexual behavior – tend to be nonviolent, Dr. Mario F. Mendez explained at the annual meeting of the American Neuropsychiatric Association.

In contrast, demented patients whose functional neuroimaging studies show more prominent temporal and parieto-occipital pathology are more likely to come to legal attention because of their nonimpulsive sociopathic acts, which are often violent in nature, said Dr. Mendez, professor of neurology and psychiatry and biobehavioral sciences at the University of California, Los Angeles.

Mechanistically, sociopathy in dementia results either from disinhibition secondary to frontal-predominant disease (such as vascular dementia, Huntington’s disease, or frontotemporal dementia), or from agitation and paranoia with memory and language impairment leading to misinterpretation of benign environmental cues as being hostile. Individuals with the nonimpulsive form tend to have advanced Alzheimer’s disease.

The hallmark of the impulsive form of sociopathy in dementia is lesions of the ventromedial prefrontal cortex, often with an additional contribution from the anterior temporolimbic area.

"Changes to the adjacent orbital frontal cortex region may be critical, resulting in impaired control of impulsive responses to tempting situations. Affected patients have impaired automatic feedback from social cues, especially angry or aversive expressions," according to Dr. Mendez, who is also director of the neurobehavior unit at the VA Greater Los Angeles Healthcare System.

As in psychopathy, sociopathy in dementia can take the form of goal-oriented aggression. But psychopathy differs from sociopathy in dementia in several key ways: Psychopathy first appears as antisocial behavior in childhood. And it is distinguished by additional features that are not found in sociopathy in dementia, including manipulation, callousness, grandiosity, sensation seeking, and deception.

To highlight the two broad types of sociopathy in dementia, Dr. Mendez presented his observational study of 33 affected patients. All of them had become involved with the legal system as a result of their behavior. In all, 22 were tagged for impulsive sociopathic acts and 11 for nonimpulsive acts.

The most common diagnoses among the 33 demented patients were Alzheimer’s disease, frontotemporal dementia, and vascular dementia or anoxic encephalopathy. Collectively, they accounted for 20 cases. But sociopathy has also been seen in association with many other brain diseases as well, including epilepsy, Parkinsonian syndromes, stroke, traumatic brain injury, and subarachnoid hemorrhage, Dr. Mendez said.

The 11 nonimpulsive patients were significantly older (mean age, 74 years), compared with age 62 for the impulsive group. The nonimpulsive group was also more impaired in language and/or cognition as reflected by their mean Mini-Mental State Exam score of 19.72, compared with 24.12 in the impulsive group.

On the Neuropsychiatric Inventory, the nonimpulsive patients scored higher on agitation, aggression, delusions, irritability, and depression. They demonstrated more impairment of language on the Category Fluency Test and the Mini-Boston Naming Test, performed worse on three-dimensional construction tasks, and their CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) scores also showed greater memory impairment.

Pathological stealing of unneeded items was common among the impulsive group. Unlike kleptomania, however, there is no increasing tension before these acts of pathological stealing, and no release of tension afterward. Inappropriate sexual behavior in the impulsive group included prolonged staring, indecent exposure, and unsolicited sexual approach.

Physical assaults were largely confined to the nonimpulsive group. "More severe memory/language deficits may lead to misinterpretations, paranoia, and suspicion. These patients can have paramnesic delusions, such as delusions of theft. They don’t remember where they left things and conclude malevolent intent. That’s very common in midstage Alzheimer’s disease," Dr. Mendez said.

In the impulsive sociopathy group, 82% of patients had disproportionate frontal-caudate abnormalities on functional neuroimaging, compared with 36% in the nonimpulsive group.

Drug treatment should target the mechanism underlying the sociopathic behavior, he said. For disinhibited impulsive patients, he and his UCLA colleagues often will titrate an SSRI up to the equivalent of 200 mg/day of sertraline. He has also been highly impressed with the effects of lamotrigine (Lamictal). In addition, he has successfully targeted disinhibition using valproic acid, divalproex, or propranolol.

Trazodone (Oleptro) Dr. Mendez’s first-line agent when the underlying mechanism of sociopathy in dementia is agitation and/or paranoia. But if trazodone proves ineffective, he doesn’t hesitate to move to the newer antipsychotic drugs, despite the black box warnings.

"To me, the most effective drug for delusional beliefs in, say, Alzheimer’s disease has been low-dose risperidone," Dr. Mendez said.

He declared having no relevant financial interests.

DENVER – Acquired sociopathy resulting from dementia is a common condition with two broad forms that require very different treatment strategies.

Demented patients who commit impulsive, sociopathic acts without emotion or concern for the consequences most often display frontal-caudate disturbances on functional neuroimaging. Their impulsive acts – for example, pathological stealing or disinhibited sexual behavior – tend to be nonviolent, Dr. Mario F. Mendez explained at the annual meeting of the American Neuropsychiatric Association.

In contrast, demented patients whose functional neuroimaging studies show more prominent temporal and parieto-occipital pathology are more likely to come to legal attention because of their nonimpulsive sociopathic acts, which are often violent in nature, said Dr. Mendez, professor of neurology and psychiatry and biobehavioral sciences at the University of California, Los Angeles.

Mechanistically, sociopathy in dementia results either from disinhibition secondary to frontal-predominant disease (such as vascular dementia, Huntington’s disease, or frontotemporal dementia), or from agitation and paranoia with memory and language impairment leading to misinterpretation of benign environmental cues as being hostile. Individuals with the nonimpulsive form tend to have advanced Alzheimer’s disease.

The hallmark of the impulsive form of sociopathy in dementia is lesions of the ventromedial prefrontal cortex, often with an additional contribution from the anterior temporolimbic area.

"Changes to the adjacent orbital frontal cortex region may be critical, resulting in impaired control of impulsive responses to tempting situations. Affected patients have impaired automatic feedback from social cues, especially angry or aversive expressions," according to Dr. Mendez, who is also director of the neurobehavior unit at the VA Greater Los Angeles Healthcare System.

As in psychopathy, sociopathy in dementia can take the form of goal-oriented aggression. But psychopathy differs from sociopathy in dementia in several key ways: Psychopathy first appears as antisocial behavior in childhood. And it is distinguished by additional features that are not found in sociopathy in dementia, including manipulation, callousness, grandiosity, sensation seeking, and deception.

To highlight the two broad types of sociopathy in dementia, Dr. Mendez presented his observational study of 33 affected patients. All of them had become involved with the legal system as a result of their behavior. In all, 22 were tagged for impulsive sociopathic acts and 11 for nonimpulsive acts.

The most common diagnoses among the 33 demented patients were Alzheimer’s disease, frontotemporal dementia, and vascular dementia or anoxic encephalopathy. Collectively, they accounted for 20 cases. But sociopathy has also been seen in association with many other brain diseases as well, including epilepsy, Parkinsonian syndromes, stroke, traumatic brain injury, and subarachnoid hemorrhage, Dr. Mendez said.

The 11 nonimpulsive patients were significantly older (mean age, 74 years), compared with age 62 for the impulsive group. The nonimpulsive group was also more impaired in language and/or cognition as reflected by their mean Mini-Mental State Exam score of 19.72, compared with 24.12 in the impulsive group.

On the Neuropsychiatric Inventory, the nonimpulsive patients scored higher on agitation, aggression, delusions, irritability, and depression. They demonstrated more impairment of language on the Category Fluency Test and the Mini-Boston Naming Test, performed worse on three-dimensional construction tasks, and their CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) scores also showed greater memory impairment.

Pathological stealing of unneeded items was common among the impulsive group. Unlike kleptomania, however, there is no increasing tension before these acts of pathological stealing, and no release of tension afterward. Inappropriate sexual behavior in the impulsive group included prolonged staring, indecent exposure, and unsolicited sexual approach.

Physical assaults were largely confined to the nonimpulsive group. "More severe memory/language deficits may lead to misinterpretations, paranoia, and suspicion. These patients can have paramnesic delusions, such as delusions of theft. They don’t remember where they left things and conclude malevolent intent. That’s very common in midstage Alzheimer’s disease," Dr. Mendez said.

In the impulsive sociopathy group, 82% of patients had disproportionate frontal-caudate abnormalities on functional neuroimaging, compared with 36% in the nonimpulsive group.

Drug treatment should target the mechanism underlying the sociopathic behavior, he said. For disinhibited impulsive patients, he and his UCLA colleagues often will titrate an SSRI up to the equivalent of 200 mg/day of sertraline. He has also been highly impressed with the effects of lamotrigine (Lamictal). In addition, he has successfully targeted disinhibition using valproic acid, divalproex, or propranolol.

Trazodone (Oleptro) Dr. Mendez’s first-line agent when the underlying mechanism of sociopathy in dementia is agitation and/or paranoia. But if trazodone proves ineffective, he doesn’t hesitate to move to the newer antipsychotic drugs, despite the black box warnings.

"To me, the most effective drug for delusional beliefs in, say, Alzheimer’s disease has been low-dose risperidone," Dr. Mendez said.

He declared having no relevant financial interests.