Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease
Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, Kaplan A, La Rue A et al.. JAMA, 1995-03-01
Topic: Amyloid, tau and blood-test diagnosis
Objective Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. Design After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. Setting University medical center. Patients At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). Main outcome measures Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. Results Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. Conclusions These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Small, G. W., Mazziotta, J. C., Collins, M. T., Baxter, L. R., Phelps, M. E., Mandelkern, M. A., et al. (1995). Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. https://doi.org/10.1001/jama.1995.03520360056039
Vancouver
Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. 1995. doi:10.1001/jama.1995.03520360056039. PMID: 7884953.
BibTeX
@article{small1995-7884953,
author = {Small, G. W. and Mazziotta, J. C. and Collins, M. T. and Baxter, L. R. and Phelps, M. E. and Mandelkern, M. A. and Kaplan, A. and La Rue, A. and others},
title = {{Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease}},
journal = {JAMA},
year = {1995},
doi = {10.1001/jama.1995.03520360056039},
pmid = {7884953},
url = {https://doi.org/10.1001/jama.1995.03520360056039}
}
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.
Key findings
- To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4.
- Results Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4.
- Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4.
- Conclusions These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD.
Why it matters
In 1995, researchers used brain PET scans to compare 31 middle-aged relatives of people with Alzheimer's (all had at least two affected relatives, mild memory complaints and normal test scores). The 12 who carried the APOE ε4 gene variant had lower glucose use in the parietal lobes and more left-right imbalance than the 19 who did not. This was a single comparison with no follow-up, so it shows an association in a selected family-history group; it does not show that these brain changes lead to dementia.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designlongitudinal study
- Participants12
- Evidence strengthModerate
How this study scored 65/100
Published in a top-tier 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 | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (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 | 1995 — older than 20 years, still counted |
| Sample size | 1 / 4 | 12 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 | 6 / 7 | Cited 586 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.8 citations a year over 33 year(s) since 1995 |
| Impact for its field and year | 5 / 6 | Cited 24.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 43 other studies in this library |
| Still being cited | 1 / 4 | Cited 13 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 | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 7884953) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 65 / 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.
Related
Studies in the library that share something with this one. The line above each title says what.
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
43 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Genetics
Also tagged “precursor”
1,337 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,337 tagged studies.