Exploring the association between mild behavioral impairment and plasma p-tau217: Implications for early detection of Alzheimer's disease

Abstract

INTRODUCTION: Mild behavioral impairment (MBI), marked by late-onset persistent neuropsychiatric symptoms (NPS), may signal early dementia risk. While MBI is linked to previously established amyloid-beta (Aβ) and tau biomarkers, its association with plasma p-tau217, a promising blood-based biomarker for Alzheimer's disease (AD), remains unexplored. Here, we investigated the association between MBI and plasma p-tau217 in dementia-free individuals from the Alzheimer's Disease Neuroimaging Initiative. METHODS: MBI was defined using the Neuropsychiatric Inventory (NPI) data. Linear regression assessed the association between NPS status and continuous p-tau217 levels, while logistic regression modeled the association between NPS status and p-tau217 positivity, using a study-specific cutoff. Models adjusted for age, sex, education, and cognitive diagnosis. RESULTS: Among 101 participants (mean age = 72.0 ± 6.5; 44.6% female), those with MBI had higher plasma p-tau217 levels (β = 36.4%; 95% confidence interval [CI]: 2.2–82.0, p = 0.04) and higher odds of being p-tau217 positive (odds ratio [OR] = 3.06, 95% CI: 1.14–8.70, p = 0.03) than MBI- participants. DISCUSSION: Findings support the role of MBI in AD risk stratification. Highlights: Mild behavioral impairment (MBI) is linked to elevated plasma p-tau217, a specific Alzheimer's disease biomarker. MBI increases the odds of plasma p-tau217 positivity in dementia-free individuals. Findings support MBI as an early indicator for Alzheimer's disease risk. MBI assessment can improve biomarker-based screening and clinical trial efficiency.