Mild behavioral impairment symptom severity predicts tau hyperphosphorylation assessed by plasma p‐tau181 across the Alzheimer’s disease spectrum

Abstract

AbstractBackgroundMild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by the emergence of persistent non‐cognitive neuropsychiatric symptoms (NPS) in older adults, representing an at‐risk state for dementia and a potential marker of Alzheimer’s disease (AD). However, few studies have investigated associations between MBI and plasma biomarkers of AD pathophysiology, specifically tau hyperphosphorylation.MethodIndividuals across the AD spectrum (cognitively unimpaired (CU) and impaired (CI)) were selected from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort. MBI was assessed using the MBI‐Checklist (MBI‐C), which assesses NPS severity in five subdomains: decreased motivation (apathy), emotional dysregulation (mood/anxiety symptoms), impulse dyscontrol (agitation, impulsivity, abnormal reward salience), social inappropriateness (impaired social cognition), and abnormal thoughts/perception (psychosis). Plasma levels of p‐tau181 were quantified in all individual, and log‐transformed due to right skew. Spearman correlation analysis investigated cross‐sectional associations between plasma p‐tau181 and MBI‐C scores, and between baseline plasma p‐tau181 and annual change in MBI‐C. Multivariable linear regression analyses assessed the ability of cross‐sectional and longitudinal MBI‐C scores to predict plasma p‐tau181, adjusting for age, sex, education, and diagnostic group (CU/CI, Aβ +/‐).ResultCross‐sectional MBI data were available for 211 individuals, with longitudinal data available for 128 individuals (). Significant correlations were found between plasma p‐tau181 and MBI‐C total and apathy scores in the cross‐sectional sample (Figure A). Further, significant correlations were found with plasma p‐tau181 and the annual change in MBI‐C total and apathy scores (Figure B). These associations were corroborated by significant standardized and adjusted regression coefficients from multivariate regression models, which showed that baseline and longitudinal MBI‐C total and apathy score predicted plasma level of p‐tau181 (Figure C).ConclusionOur study provides novel findings on the association between MBI and tau hyperphosphorylation assessed using plasma biomarkers in an AD cohort. These results add to the existing evidence for MBI as a clinical manifestation of AD pathology and support the use of the MBI‐C as an enrichment tool for clinical trial enrollment and therapeutic intervention.