Modeling the progression of neuropsychiatric symptoms in Alzheimer’s disease with PET-based Braak staging
Arthur C. Macedo, Joseph Therriault, Cécile Tissot, Étienne Aumont, Stijn Servaes, Nesrine Rahmouni, Jaime Fernandez‐Arias, Firoza Z Lussier, Yi-Ting Wang, Kok Pin Ng, Marie Vermeiren, Gleb Bezgin, Kely Quispialaya Socualaya, Jenna Stevenson, Seyyed Ali Hosseini, Mira Chamoun, João Pedro Ferrari‐Souza, Pâmela C.L. Ferreira, Bruna Bellaver, Douglas Teixeira Leffa, Paolo Vitali, Eduardo R. Zimmer, Zahinoor Ismail, Tharick A. Pascoal, Serge Gauthier, Pedro Rosa‐Neto
Abstract
In Alzheimer’s disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum. Participants were assigned a Braak stage at baseline and followed for 1.97 (s.d. 0.62) years. NPS were investigated using the Mild Behavioral Impairment Checklist (MBI-C) and the Neuropsychiatric Inventory Questionnaire severity (NPI-Q-S) and distress (NPI-Q-D) scales. Multiple linear regressions (MLR) assessed the association of Braak stages with baseline NPS and the annual change in NPS scores. At baseline, stages I-II, III-IV, and V-VI were associated with higher MBI-C, NPI-Q-S, and NPI-Q-D scores. Stages V-VI were associated with a significant annual increase in MBI-C scores. These findings suggest that tau accumulation may manifest clinically with an increase in NPS, which seems to be an early event in AD pathophysiology. Moreover, PET-based Braak staging appears to be a good predictor of NPS severity progression. • Neuropsychiatric symptoms are linked to tau pathology from the early disease stages. • Neuropsychiatric symptoms increase as tau pathology becomes more severe. • Tau accumulation may precede the onset of neuropsychiatric symptoms. • PET-based Braak staging predicts future behavioral symptoms in Alzheimer's disease.