Effect of genetic and vascular risk factors on rates of cognitive decline in early-onset and late-onset Alzheimer's disease

Background: Although previous studies have shown that cognitive decline in Alzheimer's disease (AD) is associated with various risk factors, they primarily focused on late-onset AD (LOAD). Objective: We aim to evaluate the differential impact of risk factors on the cognitive decline between early-onset AD (EOAD, onset < 65 years) and LOAD (onset (Formula presented.) 65 years) and explore the longitudinal effect of Apolipoprotein E allele 4 (APOE ε4) on cortical atrophy in both cohorts. Methods: Using data from 212 EOAD and 1101 LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI), we conducted multivariable mixed-effect models to evaluate the impact of APOE ε4, education, hypertension, diabetes, dyslipidemia, and body mass index on cognitive performance. Preprocessed MRI data were utilized for longitudinal parametric mapping. Results: APOE ε4 carriers in both groups showed significantly accelerated declines in language, verbal memory, executive function, and general cognition. By controlling other significant risk factors, APOE ε4 carriers showed faster declines in language and verbal memory in both groups. Females exhibited accelerated declines in Language and verbal memory in the EOAD and LOAD cohorts respectively. LOAD individuals with hypertension showed faster declines while overweight and obese participants displayed slower declines in both cohorts across all domains except visuospatial. Notably, APOE ε4 status was associated with longitudinal cortical atrophy in the LOAD cohort but not in the EOAD cohort. Conclusions: Known risk factors for AD were associated with cognitive decline in both EOAD and LOAD cohorts.