APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging
Thambisetty M, Beason-Held L, An Y, Kraut MA, Resnick SM.. Archives of neurology, 2010-01-01
Topic: Brain proteins, microglia and lab models
Objective To study differences in longitudinal changes in regional cerebral blood flow (rCBF) between apolipoprotein E (APOE) epsilon4 carriers and noncarriers in nondemented older adults from the Baltimore Longitudinal Study of Aging using positron emission tomography in order to determine whether there are regionally specific longitudinal changes in rCBF in APOE epsilon4 carriers that might be related to its well-established role as a genetic risk factor for Alzheimer disease. Design, setting, and participants Using oxygen 15 ([(15)O])-labeled water positron emission tomography and voxel-based analysis, we compared changes in rCBF over an 8-year period between 29 nondemented APOE epsilon4 carriers and 65 noncarriers older than 55 years. Serial neuropsychological data were collected for all participants. Results Widespread differences were observed in longitudinal change in rCBF between epsilon4 carriers and noncarriers. The predominant pattern was greater rCBF decline in epsilon4 carriers. These differences were observed in the frontal, parietal, and temporal cortices. The affected brain regions were those especially vulnerable to pathological changes in Alzheimer disease. Both epsilon4 carriers and noncarriers remained free of clinical diagnoses of dementia or mild cognitive impairment during the course of the study. Conclusions Our findings suggest that APOE epsilon4-mediated risk for Alzheimer disease is associated with widespread decline in rCBF over time that precedes the onset of dementia. Accelerated rates of decline in brain function in APOE epsilon4 carriers may contribute to an increased risk for Alzheimer disease and a younger age at onset.
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APA 7th
Thambisetty, M., Beason-Held, L., An, Y., Kraut, M. A., & Resnick, S. M. (2010). APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging. Archives of neurology. https://doi.org/10.1001/archneurol.2009.913
Vancouver
Thambisetty M, Beason-Held L, An Y, Kraut MA, Resnick SM. APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging. Archives of neurology. 2010. doi:10.1001/archneurol.2009.913. PMID: 20065135.
BibTeX
@article{thambisetty2010-20065135,
author = {Thambisetty, M. and Beason-Held, L. and An, Y. and Kraut, M. A. and Resnick, S. M.},
title = {{APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging}},
journal = {Archives of neurology},
year = {2010},
doi = {10.1001/archneurol.2009.913},
pmid = {20065135},
url = {https://doi.org/10.1001/archneurol.2009.913}
}
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Key findings
- Results Widespread differences were observed in longitudinal change in rCBF between epsilon4 carriers and noncarriers.
- Conclusions Our findings suggest that APOE epsilon4-mediated risk for Alzheimer disease is associated with widespread decline in rCBF over time that precedes the onset of dementia.
- Accelerated rates of decline in brain function in APOE epsilon4 carriers may contribute to an increased risk for Alzheimer disease and a younger age at onset.
Why it matters
In nondemented older adults, APOE epsilon4 carriers showed greater decline in regional cerebral blood flow over 8 years than noncarriers, in brain regions vulnerable to Alzheimer disease. This suggests that APOE epsilon4-related risk involves widespread decline in brain blood flow that precedes dementia, though the study did not test any treatment.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for 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 (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (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 | 2010 — within 20 year(s) of the newest study here |
| 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 | 5 / 7 | Cited 210 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.7 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 3 / 6 | Cited 7.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 2 / 4 | Cited 40 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Susan M. Resnick: h-index 117 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20065135) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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Read the original
- DOI: 10.1001/archneurol.2009.913
- PubMed: 20065135
- 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).
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