Peter S Myers1, John L O'Donnell1, Joshua J Jackson1, Christina N Lessov-Schlaggar1, Rebecca L Miller1, Erin R Foster1, Carlos Cruchaga1, Bruno A Benitez1, Paul T Kotzbauer1, Joel S Perlmutter1, Meghan C Campbell2. 1. From the Department of Neurology (P.S.M., J.L.O., R.L.M., E.R.F., C.C., P.T.K., J.S.P., M.C.C.), Department of Psychiatry (C.N.L.-S., E.R.F., C.C., B.A.B.), Program in Occupational Therapy (E.R.F., J.S.P.), Department of Genetics (C.C.), Department of Radiology (J.S.P., M.C.C.), Department of Neuroscience (J.S.P.), and Program in Physical Therapy (J.S.P.), Washington University School of Medicine; and Department of Psychological and Brain Sciences (J.J.J.), Washington University in St. Louis, MO. 2. From the Department of Neurology (P.S.M., J.L.O., R.L.M., E.R.F., C.C., P.T.K., J.S.P., M.C.C.), Department of Psychiatry (C.N.L.-S., E.R.F., C.C., B.A.B.), Program in Occupational Therapy (E.R.F., J.S.P.), Department of Genetics (C.C.), Department of Radiology (J.S.P., M.C.C.), Department of Neuroscience (J.S.P.), and Program in Physical Therapy (J.S.P.), Washington University School of Medicine; and Department of Psychological and Brain Sciences (J.J.J.), Washington University in St. Louis, MO. meghanc@wustl.edu.
Abstract
BACKGROUND AND OBJECTIVES: 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. METHODS: 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-amyloid42 [β-amyloid]), a β-amyloid PET scan, and/or provided a blood sample for APOE 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, and 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. RESULTS: Baseline measures of CSF β-amyloid predicted decline for memory (p = 0.04) and overall cognitive function (p = 0.01). APOE genotypes showed a significant group (ε4+, ε4-) effect such that ε4+ individuals declined faster than ε4- individuals in visuospatial function (p = 0.03). Baseline β-amyloid PET significantly predicted decline in all cognitive measures (all p ≤ 0.004). Neither baseline CSF α-synuclein nor tau predicted cognitive decline. All 3 β-amyloid--related metrics (CSF, PET, APOE) also predicted time to dementia. Models with β-amyloid PET as a predictor fit the data the best. DISCUSSION: Presence or risk of β-amyloid accumulation consistently predicted cognitive decline and time to dementia in PD. This suggests that β-amyloid has high potential as a prognostic indicator and biomarker for cognitive changes in PD.
BACKGROUND AND OBJECTIVES: 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. METHODS: 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-amyloid42 [β-amyloid]), a β-amyloid PET scan, and/or provided a blood sample for APOE 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, and 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. RESULTS: Baseline measures of CSF β-amyloid predicted decline for memory (p = 0.04) and overall cognitive function (p = 0.01). APOE genotypes showed a significant group (ε4+, ε4-) effect such that ε4+ individuals declined faster than ε4- individuals in visuospatial function (p = 0.03). Baseline β-amyloid PET significantly predicted decline in all cognitive measures (all p ≤ 0.004). Neither baseline CSF α-synuclein nor tau predicted cognitive decline. All 3 β-amyloid--related metrics (CSF, PET, APOE) also predicted time to dementia. Models with β-amyloid PET as a predictor fit the data the best. DISCUSSION: Presence or risk of β-amyloid accumulation consistently predicted cognitive decline and time to dementia in PD. This suggests that β-amyloid has high potential as a prognostic indicator and biomarker for cognitive changes in PD.
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