Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts
Buckley RF, Mormino EC, Amariglio RE, Properzi MJ, Rabin JS, Lim YY, Papp KV, Jacobs HIL et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2018-05-24
Topic: Amyloid, tau and blood-test diagnosis
Introduction Our objective was to investigate the effect of sex on cognitive decline within the context of amyloid β (Aβ) burden and apolipoprotein E genotype. Methods We analyzed sex-specific effects on Aβ-positron emission tomography, apolipoprotein, and rates of change on the Preclinical Alzheimer Cognitive Composite-5 across three cohorts, such as the Alzheimer's Disease Neuroimaging Initiative, Australian Imaging, Biomarker and Lifestyle, and Harvard Aging Brain Study (n = 755; clinical dementia rating = 0; age (standard deviation) = 73.6 (6.5); female = 55%). Mixed-effects models of cognitive change by sex, Aβ-positron emission tomography, and apolipoprotein ε4 were examined with quadratic time effects over a median of 4 years of follow-up. Results Apolipoprotein ε4 prevalence and Aβ burden did not differ by sex. Sex did not directly influence cognitive decline. Females with higher Aβ exhibited faster decline than males. Post hoc contrasts suggested that females who were Aβ and apolipoprotein ε4 positive declined faster than their male counterparts. Discussion Although Aβ did not differ by sex, cognitive decline was greater in females with higher Aβ. Our findings suggest that sex may play a modifying role on risk of Alzheimer's disease-related cognitive decline.
Key findings
- Results Apolipoprotein ε4 prevalence and Aβ burden did not differ by sex.
- Post hoc contrasts suggested that females who were Aβ and apolipoprotein ε4 positive declined faster than their male counterparts.
- Our findings suggest that sex may play a modifying role on risk of Alzheimer's disease-related cognitive decline.
Why it matters
In 755 people without dementia (mean age 73.6) pooled from three research cohorts and followed for a median of 4 years, women and men had similar amyloid levels and APOE ε4 rates, and sex alone did not change how fast thinking scores declined. However, women with higher amyloid declined faster than men, and an exploratory (post hoc) analysis suggested the same for women who were both amyloid- and ε4-positive. The authors conclude sex "may play a modifying role" in Alzheimer's-related decline. This is an observational finding, and no treatment or prevention was tested.
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Study details
- Participants755
- Evidence strengthLow
How this study scored 58/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 56 of the 96 points we could judge it on, which is 58 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 755 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 279 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.9 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 18.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 25 other studies in this library |
| Still being cited | 3 / 4 | Cited 101 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 18 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29803541) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 56 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 56 of the 96 points we could judge it on is 58 out of 100. |
| Total | 58 / 100 | — |
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Read the original
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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
Buckley, R. F., Mormino, E. C., Amariglio, R. E., Properzi, M. J., Rabin, J. S., Lim, Y. Y., et al. (2018). Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1016/j.jalz.2018.04.010
Vancouver
Buckley RF, Mormino EC, Amariglio RE, Properzi MJ, Rabin JS, Lim YY, et al. Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2018. doi:10.1016/j.jalz.2018.04.010. PMID: 29803541.
BibTeX
@article{buckley2018-29803541,
author = {Buckley, R. F. and Mormino, E. C. and Amariglio, R. E. and Properzi, M. J. and Rabin, J. S. and Lim, Y. Y. and Papp, K. V. and Jacobs, H. I. L. and others},
title = {{Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2018},
doi = {10.1016/j.jalz.2018.04.010},
pmid = {29803541},
url = {https://doi.org/10.1016/j.jalz.2018.04.010}
}
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