Mild behavioral impairment and risk of incident dementia: A systematic review and meta-analysis
TL;DR
This systematic review evaluated longitudinal evidence on the association between MBI and incident dementia, including conversion rates, dementia subtypes, domain-specific risk patterns, and biomarker correlates, finding MBI seems to represent a clinically meaningful syndrome that identifies individuals at elevated risk for dementia.
Abstract
Background Late-life emergence of persistent behavioral changes has been recognized as a clinically meaningful sign of neurodegeneration. These neuropsychiatric symptoms, operationalized as mild behavioral impairment (MBI), represent a unique pathway through which early dementia symptoms may become observable. By capturing this neurobehavioral dimension of risk, MBI expands the traditional focus on cognitive decline and may provide a complementary framework for understanding the early manifestations of neurodegeneration. Objective This systematic review evaluated longitudinal evidence on the association between MBI and incident dementia, including conversion rates, dementia subtypes, domain-specific risk patterns, and biomarker correlates. Methods We systematically searched five databases up to November 2025. Eligible studies were longitudinal prospective or retrospective cohorts including adults ≥ 50 years without dementia at baseline, assessing MBI using ISTAART-aligned instruments and reporting incident dementia outcomes. Two reviewers independently screened studies and extracted data. Hazard ratios were synthesized using random-effects meta-analysis, with heterogeneity and publication bias formally assessed. Results Despite significant study heterogeneity, MBI was associated with increased risk of incident dementia. Alzheimer's disease was the most frequently reported outcome. Among different neurobehavioral domains, apathy and affective dysregulation emerged as particularly strong predictors of dementia risk. A few biomarker studies linked MBI to greater amyloid burden, elevated plasma phosphorylated tau, and structural brain changes, supporting a biological connection between MBI and early neurodegeneration. Conclusions MBI seems to represent a clinically meaningful syndrome that identifies individuals at elevated risk for dementia. Future studies must confirm the clinical and epidemiological value of MBI and/or its subdomains, exploring their biological substrates.