Modeling the progression of neuropsychiatric symptoms in Alzheimer's disease with PET-based Braak staging

Neurobiol Aging. 2024 Dec:144:127-137. doi: 10.1016/j.neurobiolaging.2024.09.009. Epub 2024 Sep 20.

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.

Keywords: Alzheimer's disease; Braak staging; Dementia; Neurofibrillary tangles; Neuropsychiatric symptom; Positron emission tomography.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / psychology
  • Brain / diagnostic imaging
  • Brain / pathology
  • Disease Progression*
  • Female
  • Humans
  • Male
  • Positron-Emission Tomography*
  • Severity of Illness Index
  • tau Proteins* / metabolism

Substances

  • tau Proteins