Enhancing Alzheimer Disease Detection Using Neuropsychiatric Symptoms: The Role of Mild Behavioural Impairment in the Revised NIA-AA Research Framework.

Abstract

BackgroundAs the prevalence of Alzheimer disease (AD) rises, early identification of at-risk individuals is essential for effective intervention. Mild behavioral impairment (MBI), which captures emergent and persistent neuropsychiatric symptoms (NPS) in later life, may enhance early detection of AD; however, its associations with 2024 NIA-AA Core 1 biomarkers remain unexplored. We investigated associations between MBI and cerebrospinal fluid (CSF) amyloid β-42 (Aβ42) and phosphorylated tau-181 (p-tau181).MethodBaseline data from 1327 dementia-free Alzheimer's Disease Neuroimaging Initiative (ADNI) participants were analyzed. Participants were classified as MBI, non-MBI NPS, or no NPS. Gaussian mixture modeling defined biomarker positivity. Logistic and multinomial logistic regressions modeled associations between NPS status and biomarker positivity or biomarker profiles, adjusting for age, sex, education, and cognition.ResultsMBI was associated with Aβ42+ (aOR = 2.26; 95% CI = 1.71-2.99), p-tau181+ (aOR = 1.72; 95% CI = 1.30-2.28), and AD continuum profile (aOR = 2.33; 95% CI = 1.73-3.14), but not with non-AD pathology. Non-MBI NPS showed no associations.ConclusionMBI may serve as a behavioral marker of AD pathology.