Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study
Dean DC, Jerskey BA, Chen K, Protas H, Thiyyagura P, Roontiva A, O'Muircheartaigh J, Dirks H et al.. JAMA neurology, 2014-01-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. Objective To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD. Design, setting, and participants Quiet magnetic resonance imaging was performed at an academic research imaging center on 162 healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders. Cross-sectional measurements were compared in the APOE ε4 carrier and noncarrier groups. White matter MWF was compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60 ε4 carriers and 102 noncarriers). Gray matter volume was compared in a subset of fifty-nine 6- to 25-month-old infants (23 ε4 carriers and 36 noncarriers), who remained asleep during the scanning session. The carrier and noncarrier groups were matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. Main outcomes and measures Automated algorithms compared regional white matter MWF and GMV in the carrier and noncarrier groups and characterized their associations with age. Results Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P Conclusions and relevance While our findings should be considered preliminary, this study demonstrates some of the earliest brain changes associated with the genetic predisposition to AD. It raises new questions about the role of APOE in normal human brain development, the extent to which these processes are related to subsequent AD pathology, and whether they could be targeted by AD prevention therapies.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Dean, D. C., Jerskey, B. A., Chen, K., Protas, H., Thiyyagura, P., Roontiva, A., et al. (2014). Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study. JAMA neurology. https://doi.org/10.1001/jamaneurol.2013.4544
Vancouver
Dean DC, Jerskey BA, Chen K, Protas H, Thiyyagura P, Roontiva A, et al. Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study. JAMA neurology. 2014. doi:10.1001/jamaneurol.2013.4544. PMID: 24276092.
BibTeX
@article{dean2014-24276092,
author = {Dean, D. C. and Jerskey, B. A. and Chen, K. and Protas, H. and Thiyyagura, P. and Roontiva, A. and O'Muircheartaigh, J. and Dirks, H. and others},
title = {{Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study}},
journal = {JAMA neurology},
year = {2014},
doi = {10.1001/jamaneurol.2013.4544},
pmid = {24276092},
url = {https://doi.org/10.1001/jamaneurol.2013.4544}
}
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
- Results Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05, after correction for multiple comparisons; GMV differences, P < .001, uncorrected for multiple comparisons).
Why it matters
In this cross-sectional imaging study, infants carrying the APOE epsilon 4 allele had differences in white matter myelin water fraction and gray matter volume compared with noncarriers. These are early structural findings in infants and do not show that any treatment or prevention is possible.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designcross-sectional
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal, and it is a snapshot of people at one point in 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 | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (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 | 2014 — 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 265 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.9 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 17.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 2 / 4 | Cited 45 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Eric M. Reiman: h-index 151 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24276092) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2013.4544
- PubMed: 24276092
- 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).
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
13 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Genetics
Also tagged “classification”
835 studies in the library carry the topic tag “classification”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 835 tagged studies.