Blood‐based Alzheimer's disease biomarkers and cognitive trajectories in older people with HIV with undetectable viral loads

Abstract INTRODUCTION Cognitive impairment among people with HIV (PWH) remains common, yet underlying mechanisms remain unclear. Alzheimer's disease (AD) is the leading cause of dementia, and blood‐based biomarkers offer a promising diagnostic alternative. We evaluated phosphorylated‐tau 217 (p‐tau217), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as predictors of cognitive decline among virologically suppressed older PWH. METHODS Thai PWH aged ≥50 years with plasma viral loads <50 copies/mL completed the Montreal Cognitive Assessment (MoCA) at baseline (2015–2017) and a follow‐up visit (2021–2024). Associations between each biomarker and cognitive trajectories were assessed using multivariate mixed‐effects models. RESULTS Among 255 participants followed for a median of 5.9 years, those in Q4 of p‐tau217 and GFAP had greater MoCA decline than Q1‐3 (p‐tau217: ‐3.3 vs. ‐1.4, p‐interaction = 0.02; GFAP: ‐2.9 vs. ‐1.3, p‐interaction = 0.03). DISCUSSION Elevated p‐tau217 and GFAP predict cognitive decline in PWH, underscoring AD and inflammatory biomarker relevance.