Neurology· 2026Q1
Role of APOE ɛ4 and ɛ2 With Longitudinal Cognitive Decline Among Those With Exceptional Longevity
- 1citations
- Q1SCImago
- 2026year
Short summary
APOE ɛ4 carriers over 90 years old experience faster decline in executive function, while APOE ɛ2 carriers show slower decline in verbal episodic memory.
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Key points
- APOE ɛ4 carriers over 90 showed similar decline in executive function and semantic memory compared to non-carriers.
- APOE ɛ2 carriers exhibited slower decline in verbal episodic memory compared to non-carriers (β = 0.07, 95% CI 0.00-0.15).
- The negative impact of APOE ɛ4 on executive function decline extends to individuals with exceptional longevity.
- Linear mixed-effects and joint models yielded similar results, accounting for the competing risk of death.
AI-generated from the title and abstract; the full text is not read.
Abstract
BACKGROUND AND OBJECTIVES: ɛ4 is the strongest genetic risk factor for late-onset Alzheimer disease, while ɛ2 is associated with decreased risk. However, it is unclear how these genotypes relate to cognitive decline among those aged older than 90+. We examined associations of ɛ4 and ɛ2 with longitudinal change in 3 cognitive domains among individuals aged 90+. METHODS: genotyping was conducted using DNA extracted from saliva. Two dichotomous exposures were defined as ɛ4 carriers (ɛ2/ɛ4, ɛ3/ɛ4, or ɛ4/ɛ4 genotypes) vs non-ɛ4-carriers with no ɛ4 allele and ɛ2 carriers (ɛ2/2, ɛ2/3 genotypes) vs non-ɛ2-carriers (ɛ3/ɛ3, ɛ2/ɛ4, ɛ3/ɛ4, or ɛ4/ɛ4). Executive function (EF), semantic memory (SM), and verbal episodic memory (VEM) were measured every 6 months on up to 11 occasions using the Spanish and English Neuropsychological Scales. Time to all-cause mortality was calculated from baseline to death. We fit linear mixed-effects (LME) models and joint models (LME and Cox proportional hazard submodels) to account for the competing risk of death. Models adjusted for age and sex. RESULTS: ɛ2 carriers had similar decline in EF (β = 0.01, 95% CI -0.05 to 0.08) and SM (β = 0.01, 95% CI -0.05 to 0.08) but slower decline in VEM (β = 0.07, 95% CI 0.00-0.15) compared with noncarriers. Longitudinal results were similar for LME and joint models. DISCUSSION: After accounting for the competing risk of death, the negative consequences of ɛ4 on EF decline extend to those with exceptional longevity.
The authors' abstract, as published at the source. Neurology, 2026 · DOI ↗
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Field: Psychiatry and Mental health
Psychiatry and Mental healthMedicine