Adults with Down syndrome (DS) face markedly elevated Alzheimer's disease risk (DS-AD), yet distinguishing DS-AD from non-AD functional decline — particularly DS Regression Disorder (DS-RD) — remains clinically challenging. Using the DSQIID caregiver questionnaire in a nationwide Japanese cohort (n=769), we identified a bimodal age distribution of functional decline: a statistically significant local peak at ~28 years (F(3,756)=5.996, p=0.0005), confirmed as non-AD by plasma p-tau181 data, followed by a later rise after age 38 consistent with DS-AD. Exploratory factor analysis identified six DSQIID domains. Critically, both DS-RD and DS-AD groups showed prominent Psychomotor Slowing, but Memory and Orientation impairment was selectively elevated in DS-AD — a finding replicated across biomarker-confirmed outpatient and clinically confirmed residential validation cohorts. These results support initiating caregiver-based DS-AD screening from age 35, with domain-level DSQIID profiling as a practical differentiation tool.