Topic: Amyloid, tau and blood-test diagnosis
Objective To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults. Methods Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE epsilon4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions. Results Nondemented older adults with an APOE epsilon4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched epsilon3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated. Conclusions The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE epsilon4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding.
Key findings
- Results Nondemented older adults with an APOE epsilon4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched epsilon3 counterparts.
- Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated.
- Conclusions The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype.
- Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE epsilon4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding.
Why it matters
In this small functional MRI study of 20 nondemented older adults, those with an APOE ε4 allele showed greater magnitude and extent of brain response during learning of new pictures than those without. The authors say the results are consistent with a compensatory hypothesis, but this is a small imaging study and does not show that any treatment, cure, or prevention is available.
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Study details
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty 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 | 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 | 2005 — 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 371 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.1 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 15.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gregory G. Brown: h-index 63 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15699382) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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Read the original
- DOI: 10.1212/01.wnl.0000150885.00929.7e
- PubMed: 15699382
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. Check the citation against the original before you use it.
APA 7th
Bondi, M. W., Houston, W. S., Eyler, L. T., & Brown, G. G. (2005). fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease. Neurology. https://doi.org/10.1212/01.wnl.0000150885.00929.7e
Vancouver
Bondi MW, Houston WS, Eyler LT, Brown GG. fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease. Neurology. 2005. doi:10.1212/01.wnl.0000150885.00929.7e. PMID: 15699382.
BibTeX
@article{bondi2005-15699382,
author = {Bondi, M. W. and Houston, W. S. and Eyler, L. T. and Brown, G. G.},
title = {{fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease}},
journal = {Neurology},
year = {2005},
doi = {10.1212/01.wnl.0000150885.00929.7e},
pmid = {15699382},
url = {https://doi.org/10.1212/01.wnl.0000150885.00929.7e}
}
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