Effect of tau burden and Lewy pathology on neuropsychiatric symptoms in Aβ-positive individuals

Abstract

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common across the Alzheimer's disease (AD) spectrum. We aimed to evaluate the effects of amyloid beta (A beta), tau, and Lewy body (LB) pathologies on NPS in A beta-positive individuals. METHODS: In 336 A beta-positive participants from the Alzheimer's Disease Neuroimaging Initiative cohort, spanning from cognitively unimpaired to those with early dementia, NPS were assessed. A beta and tau positron emission tomography were conducted. In a subgroup of 238 participants, dichotomized LB pathology was assessed by detecting alpha-synuclein seeding activity. The effects of A beta, tau, and LB pathologies on NPS were evaluated using logistic regression analyses. RESULTS: Greater tau burden was associated with delusion, agitation/aggression, irritability/lability, aberrant motor behavior, and appetite/eating disorder. In subgroup analyses, LB pathology was associated with delusion, anxiety, apathy, and sleep disturbance, independent of A beta and tau burden. DISCUSSION: Tau and LB pathologies are major determinants of NPS in A beta-positive individuals, each contributing distinct symptom profiles.