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Background: Parkinson's disease psychosis (PDPsy) is associated with increased nursing home placement and mortality and is closely linked with cognitive dysfunction. Objective: Assess the clinical and cognitive features associated with PDPsy in patients without dementia. Methods: We prospectively recruited people with Parkinson's disease (PwP) without dementia for a 3-year, longitudinal study at an outpatient movement disorders clinic. Participants completed annual visits involving assessment of motor and non-motor symptoms including neuropsychological testing. PDPsy was defined as the recurring presence of visual illusions, sense of presence, hallucinations, or delusions for at least 1 month. Using generalized estimating equations, we conducted two sets of analyses to separately assess the clinical and the cognitive predictors of PDPsy. Results: We enrolled 105 participants. At baseline, mean age was 67.8 (SD = 8.0), median disease duration was 4.9 years (IQR: 3.4–7.7), and mean MoCA was 24.8 (SD = 2.3). Prevalence of PDPsy increased over 3 years from 31% (n = 32) to 39% (n = 26). Forty-five participants (43%) experienced PDPsy. Visual illusions were most common (70%, n = 84), followed by hallucinations (58.3%, n = 70). In multivariate analysis, of the clinical variables, only depressive symptoms [OR 1.09, 95% CI: (1.03, 1.16), p = 0.004] increased the odds of PDPsy; of the cognitive variables, only Trail Making Test B-A scores [OR 1.43, 95% CI: (1.06, 1.93), p = 0.018] significantly increased the odds of PDPsy. Conclusions: In PwP without dementia, depressive symptoms were associated with increased risk of PDPsy. Executive/attentional dysfunction was also associated with PDPsy and may mark the transition from isolated minor hallucinations to more complex psychotic symptoms. [ABSTRACT FROM AUTHOR]

Objective: The generation and maintenance of goal-directed behavior is subserved by multiple brain regions that receive cholinergic inputs from the cholinergic nucleus 4 (Ch4). It is unknown if Ch4 degeneration contributes to apathy in Parkinson's disease (PD). Method: We analyzed data from 106 pre-surgical patients with PD who had brain MRIs and completed the Frontal Systems Behavior Scales (FrSBe). Eighty-eight patients also completed the Beck Depression Inventory-2nd Edition. Cholinergic basal forebrain grey matter densities (GMD) were measured by applying probabilistic maps to T1 MPRAGE sequences processed using voxel-based morphometry methods. We used linear and hierarchical regression modelling to examine the association between Ch4 GMD and the FrSBe Apathy subscale scores. We used similar methods to assess the specificity of this association and potential associations between Ch4 target regions and apathy. Results: Ch4 GMD (p =.021) and Ch123 GMD (p =.032) were significantly associated with Apathy subscale scores on univariate analysis. Ch4 GMD, but not Ch123 GMD, remained significantly associated with apathy when adjusting for age, sex, levodopa equivalent doses, and disease duration. Centromedial amygdala GMD, which receives cholinergic inputs from Ch4, was also associated with apathy. Ch4 GMD was not associated with depression or disinhibition, nor was it associated with executive dysfunction when adjusting for clinical and demographic variables. Conclusions: Ch4 GMD is specifically associated with apathy in PD. Ch4 degeneration results in cholinergic denervation of multiple cortical and limbic regions, which may contribute to the cognitive and emotional-affective processing deficits that underlie the behavioral symptoms of apathy. [ABSTRACT FROM AUTHOR]