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Patterns of brain activation in people at risk for Alzheimer's disease
Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, Small GW.. The New England journal of medicine, 2000-08-01
Topic: Amyloid, tau and blood-test diagnosis
Background The epsilon4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease, we performed APOE genotyping and functional magnetic resonance imaging (MRI) of the brain in older persons with intact cognition. Methods We studied 30 subjects (age, 47 to 82 years) who were neurologically normal, of whom 16 were carriers of the APOE epsilon4 allele and 14 were homozygous for the APOE epsilon3 allele. The mean age and level of education were similar in the two groups. Patterns of brain activation during functional MRI scanning were determined while subjects memorized and recalled unrelated pairs of words and while subjects rested between such periods. Memory was reassessed in 14 subjects two years later. Results Both the magnitude and the extent of brain activation during memory-activation tasks in regions affected by Alzheimer's disease, including the left hippocampal, parietal, and prefrontal regions, were greater among the carriers of the APOE epsilon4 allele than among the carriers of the APOE epsilon3 allele. During periods of recall, the carriers of the APOE epsilon4 allele had a greater average increase in signal intensity in the hippocampal region (1.03 percent vs. 0.62 percent, P Conclusions Patterns of brain activation during tasks requiring memory differ depending on the genetic risk of Alzheimer's disease and may predict a subsequent decline in memory.
Key findings
- Results Both the magnitude and the extent of brain activation during memory-activation tasks in regions affected by Alzheimer's disease, including the left hippocampal, parietal, and prefrontal regions, were greater among the carriers of the APOE epsilon4 allele than among the carriers of the APOE epsilon3 allele.
Why it matters
This study found that cognitively normal APOE epsilon4 carriers had greater brain activation during memory tasks in regions affected by Alzheimer's disease than non-carriers. It examines brain responses related to genetic risk, not treatment, cure, or prevention.
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Study details
- Participants30
- Evidence strengthLow
How this study scored 62/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (The New England journal of medicine) |
| Journal's citation record | 4 / 4 | New England Journal of Medicine: journal h-index 1,505 (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 | 2000 — older than 20 years, still counted |
| Sample size | 1 / 4 | 30 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 | 7 / 7 | Cited 1,331 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 47.5 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 5 / 6 | Cited 29.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 35 other studies in this library |
| Still being cited | 3 / 4 | Cited 76 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gary W. Small: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10944562) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
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Read the original
- DOI: 10.1056/nejm200008173430701
- PubMed: 10944562
- Original source →
- Free full text: New England Journal of Medicine →
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 7 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
Bookheimer, S. Y., Strojwas, M. H., Cohen, M. S., Saunders, A. M., Pericak-Vance, M. A., Mazziotta, J. C., et al. (2000). Patterns of brain activation in people at risk for Alzheimer's disease. The New England journal of medicine. https://doi.org/10.1056/nejm200008173430701
Vancouver
Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, et al. Patterns of brain activation in people at risk for Alzheimer's disease. The New England journal of medicine. 2000. doi:10.1056/nejm200008173430701. PMID: 10944562.
BibTeX
@article{bookheimer2000-10944562,
author = {Bookheimer, S. Y. and Strojwas, M. H. and Cohen, M. S. and Saunders, A. M. and Pericak-Vance, M. A. and Mazziotta, J. C. and Small, G. W.},
title = {{Patterns of brain activation in people at risk for Alzheimer's disease}},
journal = {The New England journal of medicine},
year = {2000},
doi = {10.1056/nejm200008173430701},
pmid = {10944562},
url = {https://doi.org/10.1056/nejm200008173430701}
}
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