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.
Lindsey Kirsch-Darrow
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.