Serum cholesterol and risk of Alzheimer disease: a community-based cohort study
Li G, Shofer JB, Kukull WA, Peskind ER, Tsuang DW, Breitner JC, McCormick W, Bowen JD et al.. Neurology, 2005-10-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Objectives To examine the association of serum total cholesterol (TC) and high density lipoprotein (HDL) levels and subsequent incidence of dementia and Alzheimer disease (AD) in a population-based cohort study. Methods A cohort of cognitively intact persons, aged 65 and older, was randomly selected from Group Health Cooperative (GHC), a large health maintenance organization, and was assessed biennially for dementia. Premorbid levels of TC and HDL were obtained from a computerized clinical laboratory database at GHC. Cox proportional hazards regression was used to calculate hazard ratios (HR, 95% CI) for dementia and AD associated with quartiles of TC and HDL levels. Results Of the 2,356 eligible participants, 2,141 had at least one serum TC measure prior to the initial enrollment. Using the lowest TC quartiles as the reference group, the HR in the highest TC quartiles was not significantly elevated for dementia (1.16, 0.81 to 1.67) or for AD (1.00, 0.61 to 1.62) after adjusting for age, sex, education, baseline cognition, vascular comorbidities, body mass index, and lipid-lowering agent use. Serum HDL showed a similar lack of significant association with risk of dementia or AD. Models that included the presence of one or more APOE-epsilon4 alleles showed a typical association of epsilon4 with AD risk. This association was not materially modified by inclusion of TC level. Conclusion The data do not support an association between serum total cholesterol or high density lipoprotein in late life and subsequent risk of dementia or Alzheimer disease (AD). The increased risk of AD with APOE-epsilon4 is probably not mediated by serum total cholesterol levels.
What this study adds
Evidence grade: Moderate
This is a follow-up (cohort) study. In this community-based cohort, higher serum total cholesterol and HDL levels were not significantly associated with later development of dementia or Alzheimer's disease. The typical association of APOE-ε4 with Alzheimer's risk was not materially changed by including cholesterol level.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Li, G., Shofer, J. B., Kukull, W. A., Peskind, E. R., Tsuang, D. W., Breitner, J. C., et al. (2005). Serum cholesterol and risk of Alzheimer disease: a community-based cohort study. Neurology. https://doi.org/10.1212/01.wnl.0000178989.87072.11
Vancouver
Li G, Shofer JB, Kukull WA, Peskind ER, Tsuang DW, Breitner JC, et al. Serum cholesterol and risk of Alzheimer disease: a community-based cohort study. Neurology. 2005. doi:10.1212/01.wnl.0000178989.87072.11. PMID: 16217057.
BibTeX
@article{li2005-16217057,
author = {Li, G. and Shofer, J. B. and Kukull, W. A. and Peskind, E. R. and Tsuang, D. W. and Breitner, J. C. and McCormick, W. and Bowen, J. D. and others},
title = {{Serum cholesterol and risk of Alzheimer disease: a community-based cohort study}},
journal = {Neurology},
year = {2005},
doi = {10.1212/01.wnl.0000178989.87072.11},
pmid = {16217057},
url = {https://doi.org/10.1212/01.wnl.0000178989.87072.11}
}
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
- Cox proportional hazards regression was used to calculate hazard ratios (HR, 95% CI) for dementia and AD associated with quartiles of TC and HDL levels.
- Results Of the 2,356 eligible participants, 2,141 had at least one serum TC measure prior to the initial enrollment.
- Using the lowest TC quartiles as the reference group, the HR in the highest TC quartiles was not significantly elevated for dementia (1.16, 0.81 to 1.67) or for AD (1.00, 0.61 to 1.62) after adjusting for age, sex, education, baseline cognition, vascular comorbidities, body mass index, and lipid-lowering agent use.
- Serum HDL showed a similar lack of significant association with risk of dementia or AD.
- The increased risk of AD with APOE-epsilon4 is probably not mediated by serum total cholesterol levels.
Why it matters
In this community-based cohort, higher serum total cholesterol and HDL levels were not significantly associated with later development of dementia or Alzheimer's disease. The typical association of APOE-ε4 with Alzheimer's risk was not materially changed by including cholesterol level.
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Study details
- Study designcohort study
- Evidence strengthModerate
How this study scored 57/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2005 — older than 20 years, still counted |
| 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 160 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.0 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 5.3× 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 | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Eric B. Larson: h-index 63 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16217057) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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