Topic: Amyloid, tau and blood-test diagnosis
Background Clinical and epidemiologic studies suggest that patients with Alzheimer disease (AD) with larger head circumference have better cognitive performance at the same level of brain pathology than subjects with smaller head circumference. Methods A total of 270 patients with AD participating in the Multi-Institutional Research in Alzheimer's Genetic Epidemiology (MIRAGE) study underwent cognitive testing, APOE genotyping, and MRI of the brain in a cross-sectional study. Linear regression analysis was used to examine the association between cerebral atrophy, as a proxy for AD pathology, and level of cognitive function, adjusting for age, duration of AD symptoms, gender, head circumference, APOE genotype, diabetes mellitus, hypertension, major depression, and ethnicity. An interaction term between atrophy and head circumference was introduced to explore if head circumference modified the association between cerebral atrophy and cognition. Results There was a significant inverse association between atrophy and cognitive function, and a significant interaction between atrophy and head circumference. With greater levels of atrophy, cognition was higher for individuals with greater head circumference. Conclusion This study suggests that larger head circumference is associated with less cognitive impairment in the face of cerebral atrophy. This finding supports the notion that head circumference (and presumably brain size) offers protection against AD symptoms through enhanced brain reserve.
Key findings
- Background Clinical and epidemiologic studies suggest that patients with Alzheimer disease (AD) with larger head circumference have better cognitive performance at the same level of brain pathology than subjects with smaller head circumference.
- Results There was a significant inverse association between atrophy and cognitive function, and a significant interaction between atrophy and head circumference.
- Conclusion This study suggests that larger head circumference is associated with less cognitive impairment in the face of cerebral atrophy.
Why it matters
In this cross-sectional study of people with Alzheimer's disease, larger head circumference was associated with better cognition at the same level of brain atrophy. The authors suggest this supports the idea of brain reserve, but the study cannot show that head size causes or prevents anything.
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Study details
- Study designcross-sectional
- Participants270
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported 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 | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 270 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 | 5 / 7 | Cited 118 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.6 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 3 / 6 | Cited 5.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 10 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Alexander Kurz: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20625166) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0b013e3181e7ca97
- PubMed: 20625166
- 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. 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.
APA 7th
Perneczky, R., Wagenpfeil, S., Lunetta, K. L., Cupples, L. A., Green, R. C., Decarli, C., et al. (2010). Head circumference, atrophy, and cognition: implications for brain reserve in Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0b013e3181e7ca97
Vancouver
Perneczky R, Wagenpfeil S, Lunetta KL, Cupples LA, Green RC, Decarli C, et al. Head circumference, atrophy, and cognition: implications for brain reserve in Alzheimer disease. Neurology. 2010. doi:10.1212/wnl.0b013e3181e7ca97. PMID: 20625166.
BibTeX
@article{perneczky2010-20625166,
author = {Perneczky, R. and Wagenpfeil, S. and Lunetta, K. L. and Cupples, L. A. and Green, R. C. and Decarli, C. and Farrer, L. A. and Kurz, A. and others},
title = {{Head circumference, atrophy, and cognition: implications for brain reserve in Alzheimer disease}},
journal = {Neurology},
year = {2010},
doi = {10.1212/wnl.0b013e3181e7ca97},
pmid = {20625166},
url = {https://doi.org/10.1212/wnl.0b013e3181e7ca97}
}
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