Predicting Cognitive Decline in Early Alzheimer’s: Insights from East Asian Cohorts

Background While cognitive decline is inevitable in early Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI), the rate of decline varies widely. Aims This study aimed to identify groups of individuals following similar trajectories of cognitive decline, and develop a model predicting those at risk of rapid decline. Methods A longitudinal study of 251 clinic-based early AD/aMCI converters from Taiwan, with external validation in an independent Japanese cohort. Group-based trajectory modeling identified cognitive decline patterns using Mini-Mental State Examination (MMSE) scores. Baseline assessments included demographics, lifestyle factors, comorbidities, functional capacities, neuropsychiatric symptoms, neuropsychological tests, and clinical characteristics. Backward logistic regression was used to identify predictors of rapid cognitive decline. Results Two cognitive trajectories were identified: a rapid decline group (two-year MMSE decline of 5.8 ± 5.1 points) and a slower decline group (1.4 ± 2.6 points). Baseline MMSE score, instrumental activities of daily living (IADL) score, and apolipoprotein E ( APOE ) ε4 allele count were significant predictors of rapid cognitive decline. The prediction model demonstrated good discrimination in the Taiwanese cohort (The area under the curve (AUC) = 0.841, 95% confidence intervals (CI): 0.771–0.892) with sensitivity of 0.769 and specificity of 0.728, and showed acceptable discrimination (AUC = 0.715, 95% CI: 0.649–0.780) with good recalibration in the Japanese validation cohort. Conclusions This is the first clinic-based prediction model for cognitive decline in East Asian early AD/aMCI with external validation. Baseline MMSE, IADL, and APOE genotype may assist clinicians in risk stratification, disease monitoring, and individualized care planning in aging populations.