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Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia
Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J.. Proceedings of the National Academy of Sciences of the United States of America, 2003-12-19
Topic: Amyloid, tau and blood-test diagnosis
Fluorodeoxyglucose positron emission tomography (PET) studies have found that patients with Alzheimer's dementia (AD) have abnormally low rates of cerebral glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal cortex. We previously found that cognitively normal, late-middle-aged carriers of the apolipoprotein E epsilon4 allele, a common susceptibility gene for late-onset Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same brain regions as patients with probable AD. We now consider whether epsilon4 carriers have these regional brain abnormalities as relatively young adults.
Key findings
- We previously found that cognitively normal, late-middle-aged carriers of the apolipoprotein E epsilon4 allele, a common susceptibility gene for late-onset Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same brain regions as patients with probable AD.
- We now consider whether epsilon4 carriers have these regional brain abnormalities as relatively young adults.
- Apolipoprotein E genotypes were established in normal volunteers 20-39 years of age.
- Clinical ratings, neuropsychological tests, magnetic resonance imaging, and PET were performed in 12 epsilon4 heterozygotes, all with the epsilon3/epsilon4 genotype, and 15 noncarriers of the epsilon4 allele, 12 of whom were individually matched for sex, age, and educational level.
Why it matters
APOE ε4 is "a common susceptibility gene for late-onset Alzheimer's dementia", and the authors had earlier found that healthy late-middle-aged carriers show low brain glucose use in the same regions as people with Alzheimer's. This study asked whether that pattern is already present at ages 20–39, comparing 12 carriers (all with one ε4 copy) with 15 non-carriers using memory and thinking tests, MRI and PET. The record we hold describes the question and methods but not the results; it tested no treatment and cannot show that carriers will develop Alzheimer's.
Study details
- Evidence strengthLow
How this study scored 56/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 2004 — 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 981 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 40.9 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 5 / 6 | Cited 20.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 70 other studies in this library |
| Still being cited | 3 / 4 | Cited 66 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John Hardy: h-index 205 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 14688411) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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 names 8 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.
APA 7th
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., et al. (2004). Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2635903100
Vancouver
Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proceedings of the National Academy of Sciences of the United States of America. 2004. doi:10.1073/pnas.2635903100. PMID: 14688411.
BibTeX
@article{reiman2004-14688411,
author = {Reiman, E. M. and Chen, K. and Alexander, G. E. and Caselli, R. J. and Bandy, D. and Osborne, D. and Saunders, A. M. and Hardy, J.},
title = {{Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2004},
doi = {10.1073/pnas.2635903100},
pmid = {14688411},
url = {https://doi.org/10.1073/pnas.2635903100}
}
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