Maryam Ghahremani, Eric E. Smith, Zahinoor Ismail
Background Functional independence is crucial for healthy aging, and its loss is a diagnostic criterion for dementia, including Alzheimer's disease. However, functional impairment (FI) can emerge before dementia diagnosis. Early and accurate characterization of FI may help identify individuals at elevated risk of cognitive decline and dementia. Objective Exploring the utility of capturing persistent versus impersistent FI, to identify a higher-risk group for incident cognitive decline and dementia. Method Data from 11,793 cognitively normal (CN) older adults from the National Alzheimer's Coordinating Center were analyzed. Exploratory factor analysis identified four Functional Activities Questionnaire items—preparing hot drinks, preparing balanced meals, shopping, and traveling—representing primarily functional abilities. An FI composite score was calculated as the sum of these items. Persistent FI was operationalized as FI present (composite score ≥ 2) at more than two-thirds of all visits prior to cognitive decline and dementia. Comparator groups were impersistent/transient FI and no FI. Time-dependent covariate Cox models compared incidence of cognitive decline and dementia across time-dependent FI groups, adjusted for demographics, APOE ε4 status, presence of neuropsychiatric symptoms, CDR sum of boxes, and informant characteristics (age, sex, relationship, cohabitation status). Results The CN sample comprised 164 Persistent-FI (age = 75.7 ± 12.2; 59.1% female), 522 Transient-FI (age = 73.7 ± 9.5; 62.8% female), and 11,107 No-FI participants (age = 70.9 ± 8.9; 66.0% female). Persistent-FI was associated with a 2.12-fold greater incidence of cognitive decline and dementia versus No-FI (CI:1.80–2.51, p < 0.001). Transient-FI showed no significant difference (HR = 1.14, CI:0.97–1.33, p = 0.107). Conclusions Operationalizing FI-related risk based on persistence is a promising approach to incorporation of FI into dementia prognostication.