Neuropsychiatric symptoms and α-Synuclein profile of patients with Parkinson's disease dementia, dementia with Lewy bodies and Alzheimer's disease

Given the overlapping of neuropathological, neurochemical and neuropsychiatric profiles of Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), their differential diagnosis is challenging. Specific neuropsychiatric features or biomarkers, such as cerebrospinal fluid (CSF) alpha-Synuclein (alpha-Syn), may aid in differential diagnosis. This study aims to compare the neuropsychiatric and CSF alpha-Syn profiles in these conditions, and to investigate the possible association between CSF alpha-Syn levels and neuropsychiatric symptoms. We conducted a prospective cross-sectional study, between January 2013 and January 2015, with 16 PDD, 28 DLB and 19 AD patients. All participants underwent a detailed clinical, neuropsychological, neuropsychiatric [Neuropsychiatric Inventory (NPI)] and CSF alpha-Syn analysis. Significantly greater NPI Hallucinations Subitem score was found in the PDD and DLB groups compared to AD (both p < 0.001). NPI Agitation score was greater in the DLB compared to PDD group (p = 0.012). NPI Sleep score was greater in the DLB compared to AD group (p = 0.001). Total NPI score was greater in the DLB compared to AD and PDD groups. To discriminate between the DLB and AD and between DLB and PDD groups, logistic regression analysis showed that both NPI scores and alpha-Syn levels were independently associated. There was no correlation between NPI scores and alpha-Syn levels. Increased NPI scores and alpha-Syn levels are associated with greater likelihood for being in DLB than in PDD or AD groups. ROC analysis showed that the combination of NPI and alpha-Syn increases the discriminative ability of each marker alone (p < 0.001) with AUC equal to 0.95 (95% CI 0.91-0.99). NPI scores and CSF alpha-Syn levels were useful as independent variables to differentiate DLB from PDD and AD.