Differential effects of risk factors on the cognitive trajectory of early- and late-onset Alzheimer's disease

Alzheimers Res Ther. 2021 Jun 14;13(1):113. doi: 10.1186/s13195-021-00857-w.


Background: Although few studies have shown that risk factors for Alzheimer's disease (AD) are associated with cognitive decline in AD, not much is known whether the impact of risk factors differs between early-onset AD (EOAD, symptom onset < 65 years of age) versus late-onset AD (LOAD). Therefore, we evaluated whether the impact of Alzheimer's disease (AD) risk factors on cognitive trajectories differ in EOAD and LOAD.

Methods: We followed-up 193 EOAD and 476 LOAD patients without known autosomal dominant AD mutation for 32.3 ± 23.2 months. Mixed-effects model analyses were performed to evaluate the effects of APOE ε4, low education, hypertension, diabetes, dyslipidemia, and obesity on cognitive trajectories.

Results: APOE ε4 carriers showed slower cognitive decline in general cognitive function, language, and memory domains than APOE ε4 carriers in EOAD but not in LOAD. Although patients with low education showed slower cognitive decline than patients with high education in both EOAD and LOAD, the effect was stronger in EOAD, specifically in frontal-executive function. Patients with hypertension showed faster cognitive decline than did patients without hypertension in frontal-executive and general cognitive function in LOAD but not in EOAD. Patients with obesity showed slower decline in general cognitive function than non-obese patients in EOAD but not in LOAD.

Conclusions: Known risk factors for AD were associated with slower cognitive decline in EOAD but rapid cognitive decline in LOAD.

Keywords: Age; Alzheimer’s disease; Cognitive decline; Risk factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / genetics
  • Cognition
  • Humans
  • Memory
  • Risk Factors