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APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study
Breitner JC, Wyse BW, Anthony JC, Welsh-Bohmer KA, Steffens DC, Norton MC, Tschanz JT, Plassman BL et al.. Neurology, 1999-07-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To examine the prevalence of Alzheimer's disease (AD) and other dementias in relation to age, education, sex, and genotype at APOE. Recent studies suggest age heterogeneity in the risk of AD associated with the APOE genotype and a possible interaction between APOE-epsilon4 and female sex as risk factors. We studied these topics in the 5,677 elderly residents of Cache County, Utah, a population known for long life expectancy and high participation rates. Methods We screened for dementia with a brief cognitive test and structured telephone Dementia Questionnaire, then examined all individuals with apparent cognitive symptoms and a sample of others. We estimated age-specific prevalence of AD and other dementias and used multiple logistic regression models to describe relation of AD prevalence to age, sex, education, and APOE genotype. Results We found 335 demented individuals, 230 (69%) with definite, probable, or possible AD (positive predictive value versus autopsy confirmation 85%). The adjusted prevalence estimate for AD was 6.5% and for all dementias 9.6%. After age 90, the adjusted prevalence estimate for AD was 28% and for all dementias 38%. Regression models showed strong variation in AD prevalence with age, sex, education, and number of epsilon4 alleles (effect of epsilon2 not significant). Models were improved by a term for age-squared (negative coefficient) and by separate terms for interaction of age with presence of one or two epsilon4 alleles. An association of AD with female sex was ascribable entirely to individuals with epsilon4. Conclusions In participants with no epsilon4 alleles, the age-specific prevalence of AD reached a maximum and then declined after age 95. In epsilon4 heterozygotes a similar maximum was noted earlier at age 87, in homozygotes at age 73. Female sex was a risk factor for AD only in those with epsilon4. The epsilon4 allele accounted for 70% of the population attributable risk for AD.
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APA 7th
Breitner, J. C., Wyse, B. W., Anthony, J. C., Welsh-Bohmer, K. A., Steffens, D. C., Norton, M. C., et al. (1999). APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study. Neurology. https://doi.org/10.1212/wnl.53.2.321
Vancouver
Breitner JC, Wyse BW, Anthony JC, Welsh-Bohmer KA, Steffens DC, Norton MC, et al. APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study. Neurology. 1999. doi:10.1212/wnl.53.2.321. PMID: 10430421.
BibTeX
@article{breitner1999-10430421,
author = {Breitner, J. C. and Wyse, B. W. and Anthony, J. C. and Welsh-Bohmer, K. A. and Steffens, D. C. and Norton, M. C. and Tschanz, J. T. and Plassman, B. L. and others},
title = {{APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study}},
journal = {Neurology},
year = {1999},
doi = {10.1212/wnl.53.2.321},
pmid = {10430421},
url = {https://doi.org/10.1212/wnl.53.2.321}
}
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Key findings
- Recent studies suggest age heterogeneity in the risk of AD associated with the APOE genotype and a possible interaction between APOE-epsilon4 and female sex as risk factors.
- Results We found 335 demented individuals, 230 (69%) with definite, probable, or possible AD (positive predictive value versus autopsy confirmation 85%).
- Regression models showed strong variation in AD prevalence with age, sex, education, and number of epsilon4 alleles (effect of epsilon2 not significant).
Why it matters
In 5,677 older residents of Cache County, Utah, the share of people with Alzheimer's disease rose with age, peaked and then declined, and the peak came earlier with more copies of APOE-ε4: about age 95 with none, 87 with one, and 73 with two. Being female was linked to Alzheimer's only among ε4 carriers, and the study attributes 70% of the population's attributable risk to ε4. This is a one-time prevalence survey of a single long-lived community that describes associations; it does not show individual risk or onset ages, and it tests no treatment or prevention.
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Study details
- Effect size6.5%; 9.6%
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, sample size, studied in people and randomised / 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 | 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 | 1999 — 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 401 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.8 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 4 / 6 | Cited 9.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 38 other studies in this library |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Ara S. Khachaturian: h-index 7 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10430421) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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