Trajectories of decline in cognitively complex everyday activities across the Alzheimer’s disease continuum

Abstract

AbstractBackgroundAssessment of daily functioning may be used to capture clinically meaningful decline in Alzheimer’s disease (AD). In this multi‐center study, we aimed to investigate ‘instrumental activities of daily living’ (IADL) trajectories along the AD disease continuum from no symptoms to overt dementia, as defined in the 2018 National Institute on Aging – Alzheimer’s Association research framework (Jack et al., 2018).MethodA total of 1,557 individuals with longitudinal IADL data (72.1±8 years; 41% female; mean follow‐up 2.4±2 years) were selected from memory clinics and community‐based cohorts (Harvard Aging Brain Study, ADNI, National Alzheimer’s Coordinating Center, Amsterdam Dementia Cohort and EMIF‐AD PreclinAD and 90+). Amyloid positivity was determined at baseline using positron emission tomography or cerebrospinal fluid. Amyloid positive individuals (n=980) were classified into four NIA‐AA clinical stages based on cut‐offs on measures of subjective cognitive decline and cognitive functioning (Table 1, independent of IADL measures). Amyloid negative individuals without memory impairment or complaints (n=577) served as a control group. Everyday functioning was assessed using study‐partner‐based questionnaires as available in the different cohorts: the Everyday Cognition, Functional Activities Questionnaire and Amsterdam IADL Questionnaire. To allow comparison between the instruments, scores were standardized into Z‐scores using baseline means and standard deviations in the control group. Changes over time were analyzed using linear mixed models with random intercepts and slopes.ResultBaseline characteristics and distribution of individuals across stages can be found in Table 2. Baseline Z‐scores did not differ between amyloid negatives and stage 1; baseline Z‐scores were significantly lower in each following stage. A decline in function was found across the AD continuum, which accelerated along the clinical stages (Figure 1 and Table 3). From stage 2 onwards, IADL decline was faster compared to controls (β=‐0.085, 95% confidence interval = [‐0.116, ‐0.053], adjusted for age, sex, and education; Table 3).ConclusionOur results suggest that AD‐related functional decline accelerates along the AD continuum, as shown by steeper rates of decline in each successive stage in people with amyloid pathology. These findings were robust across different cohorts, and can be used to inform participant selection and trial design for AD clinical trials.