Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment
Devanand DP, Pelton GH, Zamora D, Liu X, Tabert MH, Goodkind M, Scarmeas N, Braun I et al.. Archives of neurology, 2005-06-01
Topic: Amyloid, tau and blood-test diagnosis
Background In cognitively impaired patients without dementia, the utility of apolipoprotein E (APOE) genotyping is unclear. Objective To evaluate the predictive utility of the APOE epsilon4 genotype for conversion to probable Alzheimer disease (AD). Design Naturalistic, longitudinal study. Setting Memory disorders outpatient clinic. Patients A total of 136 patients with memory complaints were determined to have mild cognitive impairment and were evaluated every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated annually. Main outcome measures Primary outcome measures included conversion to AD. Secondary outcome measures included change over time in Mini-Mental State Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score. Results The APOE epsilon4 allele was present in 25% of patients and 21% of healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of 136 patients converted to AD. APOE epsilon4 carrier status did not differ between converters (31%) and nonconverters to AD (23%, P = .3) and did not affect the time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02). In a Cox proportional hazards model stratified by age quartiles, after controlling for sex, education, MMSE score, and SRT delayed recall score, APOE epsilon4 increased the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95% confidence interval, 1.1-7.3; P = .03) but not in patients 55 to 69 years old (n = 79; P = .7). Conclusions APOE epsilon4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE epsilon4 homozygosity was associated with increased risk of conversion to AD. However, APOE epsilon4 carrier status by itself did not predict cognitive decline or conversion to AD, indicating that APOE genotyping in patients with mild cognitive impairment may have limited clinical applicability for prediction of outcome.
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APA 7th
Devanand, D. P., Pelton, G. H., Zamora, D., Liu, X., Tabert, M. H., Goodkind, M., et al. (2005). Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. Archives of neurology. https://doi.org/10.1001/archneur.62.6.975
Vancouver
Devanand DP, Pelton GH, Zamora D, Liu X, Tabert MH, Goodkind M, et al. Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. Archives of neurology. 2005. doi:10.1001/archneur.62.6.975. PMID: 15956169.
BibTeX
@article{devanand2005-15956169,
author = {Devanand, D. P. and Pelton, G. H. and Zamora, D. and Liu, X. and Tabert, M. H. and Goodkind, M. and Scarmeas, N. and Braun, I. and others},
title = {{Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment}},
journal = {Archives of neurology},
year = {2005},
doi = {10.1001/archneur.62.6.975},
pmid = {15956169},
url = {https://doi.org/10.1001/archneur.62.6.975}
}
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Key findings
- Results The APOE epsilon4 allele was present in 25% of patients and 21% of healthy controls.
- Four of 5 APOE epsilon4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02).
- Conclusions APOE epsilon4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE epsilon4 homozygosity was associated with increased risk of conversion to AD.
Why it matters
In outpatients with mild cognitive impairment, APOE ε4 carrier status was associated with conversion to Alzheimer disease after accounting for other risk factors, and ε4 homozygosity was linked to increased risk of conversion. This is about predicting who develops the disease, not about treating or preventing it.
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Study details
- Study designlongitudinal study
- Participants57
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same 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 longitudinal study following the same 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 | 1 / 4 | 57 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 119 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.2 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 6.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Richard P Mayeux: h-index 158 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Columbia University: institution h-index 1,824 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15956169) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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