Cognitive and neuropsychiatric profile of the synucleinopathies: Parkinson disease, dementia with Lewy bodies, and multiple system atrophy.

Parkinson disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) share alpha-synuclein immunoreactivity. These "synucleinopathies" have overlapping signs and symptoms, but less is known about similarities and differences in their cognitive and neuropsychiatric profiles. We compared the cognitive and neuropsychiatric profiles of individuals with PD, MSA, and DLB. Overall, the DLB group showed the most cognitive impairment, the MSA group demonstrated milder impairment, and the PD group was the least cognitively impaired. The DLB and MSA groups showed worse executive function and visuospatial skills than PD, whereas DLB showed impaired memory relative to both PD and MSA. On the neuropsychiatric screening, all groups endorsed depression and anxiety; the DLB group alone endorsed delusions and disinhibition. Consistent with their greater level of cognitive and neuropsychiatric impairment, the DLB group showed the greatest amount of functional impairment on a measure of instrumental activities of daily living (Functional Activities Questionnaire). We found that MSA subjects had cognitive difficulties that fell between the mild deficits of the PD group and the more severe deficits of the DLB group. PD, MSA, and DLB groups have similar neuropsychiatric profiles of increased depression and anxiety. Similar underlying alpha-synuclein pathology may contribute to these shared features.