The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period
Wilson RS, Schneider JA, Barnes LL, Beckett LA, Aggarwal NT, Cochran EJ, Berry-Kravis E, Bach J et al.. Archives of neurology, 2002-07-01
Topic: Brain proteins, microglia and lab models
Context Impairment of episodic memory is an early and defining feature of Alzheimer disease (AD). The apolipoprotein E (APOE) epsilon 4 allele is known to influence risk of AD but it has been difficult to establish whether it affects episodic memory differently from other cognitive functions. Objective To examine the association of epsilon 4 with decline in different cognitive systems. Design Longitudinal cohort study. Setting More than 40 groups of Catholic clergy from across the United States. Participants Older Catholic clergy members without clinical evidence of dementia at baseline underwent annual clinical evaluations for up to 6 years. Of 624 persons eligible for follow-up, 611 (98%) participated, of whom 161 (26%) had at least 1 epsilon 4 allele. They completed an average of 5.5 evaluations (range, 2-7). Main outcome measures Incident AD and annual rates of change in episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. Results The presence of epsilon 4 was associated with risk of developing AD on follow-up (relative risk, 1.92; 95% confidence interval, 1.27-2.89). In a series of random effects models, epsilon 4 was associated with impaired baseline function in episodic memory and visuospatial ability and with more rapid decline in all domains. The effect of epsilon 4 on annual decline in episodic memory (>3-fold increase) was significantly stronger than its effect on decline in other cognitive systems (P Conclusion The results suggest that the APOE epsilon 4 allele influences risk of AD by a relatively selective effect on episodic memory.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wilson, R. S., Schneider, J. A., Barnes, L. L., Beckett, L. A., Aggarwal, N. T., Cochran, E. J., et al. (2002). The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period. Archives of neurology. https://doi.org/10.1001/archneur.59.7.1154
Vancouver
Wilson RS, Schneider JA, Barnes LL, Beckett LA, Aggarwal NT, Cochran EJ, et al. The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period. Archives of neurology. 2002. doi:10.1001/archneur.59.7.1154. PMID: 12117364.
BibTeX
@article{wilson2002-12117364,
author = {Wilson, R. S. and Schneider, J. A. and Barnes, L. L. and Beckett, L. A. and Aggarwal, N. T. and Cochran, E. J. and Berry-Kravis, E. and Bach, J. and others},
title = {{The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period}},
journal = {Archives of neurology},
year = {2002},
doi = {10.1001/archneur.59.7.1154},
pmid = {12117364},
url = {https://doi.org/10.1001/archneur.59.7.1154}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Results The presence of epsilon 4 was associated with risk of developing AD on follow-up (relative risk, 1.92; 95% confidence interval, 1.27-2.89).
- In a series of random effects models, epsilon 4 was associated with impaired baseline function in episodic memory and visuospatial ability and with more rapid decline in all domains.
- The effect of epsilon 4 on annual decline in episodic memory (>3-fold increase) was significantly stronger than its effect on decline in other cognitive systems (P<.01), and at baseline, its effect on episodic memory was marginally stronger than its effect on other cognitive domains (P =.06).
Why it matters
In older Catholic clergy followed for up to 6 years, carrying the APOE epsilon4 allele was linked to a higher risk of developing Alzheimer's disease and to faster decline across several thinking abilities, especially episodic memory. This describes risk and decline patterns but does not test any treatment or prevention.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designcohort study
- Participants624
- Evidence strengthModerate
How this study scored 58/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2002 — older than 20 years, still counted |
| Sample size | 2 / 4 | 624 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 193 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.4 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 4 / 6 | Cited 10.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author David Alan Bennett: h-index 197 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Rush University Medical Center: institution h-index 670 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12117364) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 13.
Later studies that cite this one
12 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Genetics
Also tagged “precursor”
1,339 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.