Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia
Sanders AE, Wang C, Katz M, Derby CA, Barzilai N, Ozelius L, Lipton RB.. JAMA, 2010-01-01
Topic: Brain proteins, microglia and lab models
Context Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. Objective To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). Design, setting, and participants Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up--63 lost to follow-up and 7 new to the study--were excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) epsilon4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test [FCSRT], possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. Main outcome measures Memory decline and incident dementia. Results Valine allele frequency was 43.5%. A total of 40 cases of incident dementia occurred during follow-up (mean [(SD], 4.3 [3.1] years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval [CI], -0.58 to -0.29 vs 0.21 points per year of age for valine; 95% CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P = .03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P = .02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P = .04). Conclusion This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Sanders, A. E., Wang, C., Katz, M., Derby, C. A., Barzilai, N., Ozelius, L., et al. (2010). Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia. JAMA. https://doi.org/10.1001/jama.2009.1988
Vancouver
Sanders AE, Wang C, Katz M, Derby CA, Barzilai N, Ozelius L, et al. Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia. JAMA. 2010. doi:10.1001/jama.2009.1988. PMID: 20068209.
BibTeX
@article{sanders2010-20068209,
author = {Sanders, A. E. and Wang, C. and Katz, M. and Derby, C. A. and Barzilai, N. and Ozelius, L. and Lipton, R. B.},
title = {{Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia}},
journal = {JAMA},
year = {2010},
doi = {10.1001/jama.2009.1988},
pmid = {20068209},
url = {https://doi.org/10.1001/jama.2009.1988}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Context Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear.
- Objective To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD).
- Results Valine allele frequency was 43.5%.
- Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval [CI], -0.58 to -0.29 vs 0.21 points per year of age for valine; 95% CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P = .03) and no significant differences on the Digit Span or Digit Symbol Substitution tests.
- Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P = .02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P = .04).
Why it matters
In this cohort of older adults without dementia, a variant in the CETP gene was tested for links to memory decline and dementia risk. The study is observational, so it cannot show that changing this gene or related cholesterol pathways would prevent Alzheimer disease.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designcohort study
- Participants523
- Effect size43.5%
- Evidence strengthModerate
How this study scored 60/100
Published in a top-tier journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (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 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 523 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 106 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.9 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 9.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 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 | 1 / 4 | Last-listed author Amy E. Sanders: h-index 13 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Albert Einstein College of Medicine: institution h-index 973 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20068209) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
2 studies in the alzhub library list this one in their references.
Related studies in Genetics
Also tagged “amyloid-beta”
1,339 studies in the library carry the topic tag “amyloid-beta”; 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.