Impact of APOE e4 on cognitive trajectory in early‐onset vs late‐onset Alzheimer’s disease

Abstract

AbstractBackgroundAging and the apolipoprotein E e4 (APOE4) are the two major risk factors for Alzheimer’s disease (AD). Previous reports suggest that the impact of APOE4 on increasing risk for AD differs according to age. However, whether the impact of APOE4 on cognitive trajectories in AD differ according to age is not well established. Thus, we evaluated the impact of APOE4 on cognitive trajectories in early‐onset AD (EOAD) and late‐onset AD (LOAD).MethodIn this retrospective longitudinal study, we collected 807 AD patients who underwent two or more neuropsychological tests after they were diagnosed with AD. We categorized the patients into two groups according to their age at symptom onset: 222 patients with EOAD (age at onset <65 years) and 585 patients with LOAD (age at onset ≥ 65 years). Linear mixed‐effects model analyses were performed to evaluate the effects of APOE4 on cognitive changes after controlling for age, sex, and education in each group.ResultIn LOAD, APOE4 carriers showed more rapid cognitive decline compared to APOE4 noncarriers in language and visuospatial functions. However, in EOAD, APOE4 noncarriers showed more rapid cognitive decline compared to APOE4 carriers in general cognitive function and in all cognitive domains including language, visuospatial, memory, and frontal executive function.ConclusionOur data showed that APOE4 is associated with accelerated cognitive decline in LOAD whereas the association is reversed in EOAD. We suggest that in EOAD, there might be other genetic or environmental factors that overshadow the detrimental effects of APOE4.