Predicting functional decline in aging and Alzheimer's disease with PET-based Braak staging

Area of Science:

• Neuroimaging and Neurology
• Geriatric Medicine
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) is characterized by tau pathology, which progresses through Braak stages.
• PET imaging allows in vivo assessment of tau accumulation.
• The relationship between tau burden, Braak staging, and functional decline needs further elucidation.

Purpose of the Study:

• To investigate the association between PET-based Braak stages and functional impairment.
• To determine if PET-based Braak staging predicts longitudinal decline in activities of daily living (ADL).

Main Methods:

• A cohort study including cognitively unimpaired, mild cognitive impairment, and AD dementia individuals.
• Participants underwent [18F]MK6240 tau-PET imaging for baseline Braak staging.
• Functional performance assessed using Functional Activities Questionnaire, Everyday Cognition, and functional Clinical Dementia Rating sum of boxes.
• Longitudinal follow-up for a mean of 1.97 years.

Main Results:

• Higher PET-based Braak stages (III-VI) were associated with poorer baseline functional performance across all measures.
• Increased tau-PET signal in Braak regions of interest correlated with worse functional scores.
• Baseline PET-based Braak stages V-VI significantly predicted longitudinal decline in ADL performance.
• Voxelwise analysis revealed widespread cortical tau-PET associations with functional impairment.

Conclusions:

• Functional impairment severity increases with tau accumulation, as indicated by PET-based Braak staging.
• PET-based Braak staging is a valuable predictor of functional decline in the Alzheimer's disease continuum.
• This study supports the clinical utility of the PET-based Braak staging framework for assessing disease progression.