n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood
Whalley LJ, Deary IJ, Starr JM, Wahle KW, Rance KA, Bourne VJ, Fox HC.. The American journal of clinical nutrition, 2008-02-01
Topic: Brain proteins, microglia and lab models
Background Evidence for an inverse relation between dietary intake of n-3 polyunsaturated fatty acids (PUFAs) and age-related cognitive decline is inconsistent. This inconsistency may arise because the relation is present only in the absence of the apolipoprotein E epsilon4 (APOE epsilon4) allele. Objective We aimed to determine the contribution of erythrocyte n-3 PUFA content to cognitive aging in the presence or absence of the APOE epsilon4 allele. Design We followed up 120 volunteers, born in 1936, at approximate ages of 64, 66, and 68 y. Their intelligence quotient at 11 y old was available. At first follow-up, we determined APOE genotype and measured the PUFA composition of erythrocyte membranes. Six cognitive tests were administered at all follow-ups. We related cognitive performance at approximately 64 y old and cognitive changes from approximately 64 to approximately 68 y old to erythrocyte n-3 PUFA composition on recruitment and to APOE epsilon4 allele status. Results Total n-3 PUFA and docosohexaenoic acid concentrations were associated with benefits for cognition at approximately 64 y old and from approximately 64 to approximately 68 y old. After adjustment for sex, APOE epsilon4 status, and intelligence quotient at 11 y old, the effects associated with total n-3 PUFA remained significant. Cognitive benefits were associated with higher erythrocyte n-3 PUFA content but were significant only in the absence of the APOE epsilon4 allele. Conclusions These data are evidence of a gene x environment interaction for cognitive aging. They are relevant to the analysis of trials of n-3 PUFA supplements in cognitive aging and dementia prevention, and they support heterogeneity in cognitive aging and, possibly, in Alzheimer disease.
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APA 7th
Whalley, L. J., Deary, I. J., Starr, J. M., Wahle, K. W., Rance, K. A., Bourne, V. J., et al. (2008). n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood. The American journal of clinical nutrition. https://doi.org/10.1093/ajcn/87.2.449
Vancouver
Whalley LJ, Deary IJ, Starr JM, Wahle KW, Rance KA, Bourne VJ, et al. n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood. The American journal of clinical nutrition. 2008. doi:10.1093/ajcn/87.2.449. PMID: 18258638.
BibTeX
@article{whalley2008-18258638,
author = {Whalley, L. J. and Deary, I. J. and Starr, J. M. and Wahle, K. W. and Rance, K. A. and Bourne, V. J. and Fox, H. C.},
title = {{n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood}},
journal = {The American journal of clinical nutrition},
year = {2008},
doi = {10.1093/ajcn/87.2.449},
pmid = {18258638},
url = {https://doi.org/10.1093/ajcn/87.2.449}
}
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Key findings
- Results Total n-3 PUFA and docosohexaenoic acid concentrations were associated with benefits for cognition at approximately 64 y old and from approximately 64 to approximately 68 y old.
- After adjustment for sex, APOE epsilon4 status, and intelligence quotient at 11 y old, the effects associated with total n-3 PUFA remained significant.
- Cognitive benefits were associated with higher erythrocyte n-3 PUFA content but were significant only in the absence of the APOE epsilon4 allele.
Why it matters
In this follow-up study of people born in 1936, higher total n-3 polyunsaturated fatty acid content in red blood cell membranes was associated with better cognition at about age 64 and less decline to about age 68. However, these cognitive benefits were significant only in people without the APOE epsilon4 allele, so the findings do not show that n-3 fatty acids prevent Alzheimer's disease in everyone.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The American journal of clinical nutrition) |
| Journal's citation record | 3 / 4 | American Journal of Clinical Nutrition: journal h-index 499 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 180 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.0 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 4 / 6 | Cited 13.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Helen C Fox: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Edinburgh: institution h-index 1,378 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18258638) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 45 / 100 | — |
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