Observational studyJournal of Alzheimer's disease : JAD2021
APOE E2/E2 Is Associated with Slower Rate of Cognitive Decline with Age.
Observational study in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Pooled it
- A metabolomic signature of the APOE2 allele.GeroScience · 2023Pooled it
- The Association BetweenNeurology. Genetics · 2026Article
- Article
- Genetic Architecture of Cognitive Resilience in Alzheimer's Disease: Mechanisms, Pathways, and Therapeutic Implications.Neurology international · 2026Review
- Walking to protect against cognitive decline: the role of APOE genotype and sex.Biology of sex differences · 2026Article
- A Robust Serum Proteomic Signature of the E2 Allele of Apolipoprotein E.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of lipids in the effect of APOE2 on cognitive function: a causal mediation analysis.European journal of epidemiology · 2025Article
- Sex andInternational journal of molecular sciences · 2025Article
- HSV-1 as a Potential Driver of Alzheimer's Disease.Pathogens (Basel, Switzerland) · 2025Review
- Cognitive Resilience in Apolipoprotein ε4 Carrier Women Predicted by Neuron-Derived Extracellular Vesicles.Annals of clinical and translational neurology · 2025Article
- Utility of Polygenic Risk Scores in Families with Exceptional Longevity.medRxiv : the preprint server for health sciences · 2025Article
- Causal mediation analysis of the neuroprotection ofmedRxiv : the preprint server for health sciences · 2025Article
- APOE epsilon variants and composite risk of dementia, disability, and death in the health and retirement study.Journal of the American Geriatrics Society · 2024Article
- Impact of APOE ε4 and ε2 on plasma neurofilament light chain and cognition in autosomal dominant Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- Cluster Buster: A Machine Learning Algorithm for Genotyping SNPs from Raw Data.bioRxiv : the preprint server for biology · 2024Article
- Article
- Apolipoproteine andInternational journal of molecular sciences · 2024Article
- Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Characteristics and Predictors of Alzheimer's Disease Resilience Phenotype.Journal of clinical medicine · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe E4 allele of the APOE gene is known to be associated with cognitive impairment. However, a limited number of studies have examined the association between the E2 allele and longitudinal changes of cognitive function.
objectiveTo determine whether rates of cognitive change differ in carriers of the APOE E2 allele compared to other genotypes.
methodsWe conducted a secondary analysis of data from two ongoing longitudinal cohort studies, the Long Life Family Study (LLFS) and New England Centenarian Study (NECS). We included participants who had APOE genotyping data, data from longitudinal administrations of the Telephone Interview for Cognitive Status (TICS), and age, sex, and education available. We assessed whether cognitive change as measured by rate of decline in TICS score differed among people with different APOE genotypes. We used a hierarchical mixed effect model with APOE genotypes, their interactions with age, and potential confounders.
resultsAfter adjusting for sex and education, in carriers of the common E3/E3 genotype, TICS score decreased by 0.15 points per year of age. In those with the E2/E2 genotype, TICS score decreased by 0.05 points per year of age, a significantly slower rate of decline (p = 0.017). We observed no protective effect of the E2/E3 genotype on cognitive decline.
conclusionThese results suggest a protective effect of the E2/E2 genotype on a measure of global cognitive function.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.