Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment
Caselli RJ, Reiman EM, Locke DE, Hutton ML, Hentz JG, Hoffman-Snyder C, Woodruff BK, Alexander GE et al.. Archives of neurology, 2007-09-01
Topic: Brain proteins, microglia and lab models
Background Memory declines more rapidly with age in apolipoprotein E (APOE) epsilon4 carriers than in APOE epsilon4 noncarriers, and APOE epsilon4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth. Objective To show that presymptomatic APOE epsilon4 homozygotes experience greater psychometric decline at a younger age than APOE epsilon4 heterozygotes and noncarriers before the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD). Design Prospective observational study Setting Academic medical center. Participants A total of 43 APOE epsilon4 homozygotes, 59 APOE epsilon4 heterozygotes, and 112 APOE epsilon4 noncarriers aged 50 to 69 years were cognitively healthy and matched at entry according to age, educational level, and sex. Intervention Neuropsychological battery given every 2 years. Main outcome measures Predefined test and cognitive domain decline criteria applied to consecutive epochs. Results Of 214 participants, 48 showed no decline on any test, 126 showed decline on only 1 test in 1 or more domains, and 40 showed decline on 2 or more tests in 1 or more domains. Cognitive domain decline occurred in 4 of 10 APOE epsilon4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE epsilon4 heterozygotes and noncarriers (7.6%) (P = .02) and was more predictive of subsequent decline than nondomain decline (17 of 24 [70.8%] vs 29 of 70 [41.4%]; P = .01). Decline on any memory test was predictive of further decline (P Conclusions APOE epsilon4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE epsilon4 heterozygotes or noncarriers before the diagnosis of MCI and AD, thus confirming and characterizing the existence of a pre-MCI state in this genetic subset.
Key findings
- Results Of 214 participants, 48 showed no decline on any test, 126 showed decline on only 1 test in 1 or more domains, and 40 showed decline on 2 or more tests in 1 or more domains.
- Cognitive domain decline occurred in 4 of 10 APOE epsilon4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE epsilon4 heterozygotes and noncarriers (7.6%) (P = .02) and was more predictive of subsequent decline than nondomain decline (17 of 24 [70.8%] vs 29 of 70 [41.4%]; P = .01).
Why it matters
In this prospective study, APOE epsilon4 homozygotes aged 60 and older at entry showed cognitive domain decline more often than heterozygotes and noncarriers before any diagnosis of mild cognitive impairment or Alzheimer's disease. This indicates that cognitive decline can be detected earlier in people with two copies of the risk allele, but it does not provide a treatment or prevention.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Participants214
- Effect size40.0%; 7.6%; 70.8%
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design 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 | 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 | 2007 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 214 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 148 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.0 citations a year over 21 year(s) since 2007 |
| Impact for its field and year | 3 / 6 | Cited 4.7× 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 | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author David Osborne: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17846270) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Caselli, R. J., Reiman, E. M., Locke, D. E., Hutton, M. L., Hentz, J. G., Hoffman-Snyder, C., et al. (2007). Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Archives of neurology. https://doi.org/10.1001/archneur.64.9.1306
Vancouver
Caselli RJ, Reiman EM, Locke DE, Hutton ML, Hentz JG, Hoffman-Snyder C, et al. Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Archives of neurology. 2007. doi:10.1001/archneur.64.9.1306. PMID: 17846270.
BibTeX
@article{caselli2007-17846270,
author = {Caselli, R. J. and Reiman, E. M. and Locke, D. E. and Hutton, M. L. and Hentz, J. G. and Hoffman-Snyder, C. and Woodruff, B. K. and Alexander, G. E. and others},
title = {{Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment}},
journal = {Archives of neurology},
year = {2007},
doi = {10.1001/archneur.64.9.1306},
pmid = {17846270},
url = {https://doi.org/10.1001/archneur.64.9.1306}
}
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
12 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
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.