P-tau181 is longitudinally associated with a proxy measure of mild behavioral impairment among frail older adults: Insights from COGFRAIL.

INTRODUCTION: Cross-sectional studies link Alzheimer's disease (AD) pathogenesis to mild behavioral impairment (MBI), but longitudinal evidence remains limited. We examined whether plasma phosphorylated tau (p-tau)181 predicts progression of an MBI-proxy over 2 years in pre-frail and frail older adults with mild cognitive impairment. METHODS: This is a secondary analysis of the Cognitive Function and Prevalence of Amyloid Marker in Frail Older Adults study, including 174 participants (mean age = 82.9 ± 5.4 years). Plasma p-tau181 was analyzed both as a continuous variable and by tertiles. MBI was approximated using a Neuropsychiatric Inventory Questionnaire (NPI-Q)-based algorithm. RESULTS: Participants in the highest tertile showed greater progression in the number of affected NPI-Q-derived MBI domains and overall severity compared to the lowest tertile. Continuous analyses showed a similar but non-significant trend (P = 0.08). DISCUSSION: Amyloid and tau pathology may contribute not only to cognitive but also to behavioral impairment, supporting the hypothesis that MBI reflects underlying AD pathology, and may help identify individuals at higher risk of neuropsychiatric progression.