Proteinopathy and Longitudinal Cognitive Decline in Parkinson Disease

• Published in: Neurology
• Main Authors: Myers, Peter S, O'Donnell, John L, Jackson, Joshua J, Lessov-Schlaggar, Christina N, Miller, Rebecca L, Foster, Erin R, Cruchaga, Carlos, Benitez, Bruno A, Kotzbauer, Paul T, Perlmutter, Joel S, Campbell, Meghan C
• Format: Journal Article
• Language: English
• Published: United States 05.07.2022
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0000000000200344

People with Parkinson disease (PD) commonly experience cognitive decline, which may relate to increased α-synuclein, tau, and β-amyloid accumulation. This study examines whether the different proteins predict longitudinal cognitive decline in PD. All participants (PD: n = 152; controls: n = 52) were part of a longitudinal study and completed a lumbar puncture for CSF protein analysis (α-synuclein, total tau (tau), and β-amyloid-42 (β-amyloid)), a β-amyloid PET scan, and/or provided a blood sample for genotype (ε4+, ε4-), which is a risk factor for β-amyloid accumulation. Participants also had comprehensive, longitudinal clinical assessments of overall cognitive function and dementia status as well as cognitive testing of attention, language, memory, visuospatial and executive function. We used hierarchical linear growth models to examine whether the different protein metrics predict cognitive change and multivariate Cox proportional hazard models to predict time to dementia conversion. Akaike Information Criterion was used to compare models for best fit. Baseline measures of CSF β-amyloid predicted decline for memory (p = .04) and overall cognitive function (p = .01). genotypes showed a significant group (ε4+, ε4-) effect, such that ε4+ declined faster than ε4- in visuospatial function (p = .03). Baseline β-amyloid PET significantly predicted decline in all cognitive measures (all p ≤ .004). Neither baseline CSF α-synuclein nor tau predicted cognitive decline. All three β-amyloid-related metrics (CSF, PET, ) also predicted time to dementia. Models with β-amyloid PET as a predictor fit the data the best. Presence or risk of β-amyloid accumulation consistently predicted cognitive decline and time to dementia in PD. This suggests β-amyloid has high potential as a prognostic indicator and biomarker for cognitive changes in PD.