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Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study
Buckley RF, O'Donnell A, McGrath ER, Jacobs HIL, Lois C, Satizabal CL, Ghosh S, Rubinstein ZB et al.. Annals of neurology, 2022-05-17
Topic: Plasma and spinal-fluid biomarkers
Objective Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle-aged adults. Methods 328 CN participants from the Framingham Study (mean age = 57 years (±10 years), 161 women, of whom, 104 were post-menopausal) underwent tau and β-amyloid (Aβ)-PET neuroimaging. We examined global Aβ-PET, and tau-PET signal in 5 regions identified a priori as demonstrating significant sex differences in older adults (in temporal, inferior parietal, middle frontal, and lateral occipital regions). We examined sex and menopause status-related differences in each region-of-interest, using linear regressions, as well as interactions with Aβ and APOEε4 genotype. Results Women exhibited higher tau-PET signal (p < 0.002), and global Aβ-PET (p = 0.010), than men in inferior parietal, rostral middle frontal, and lateral occipital regions. Compared with age-matched men, post-menopausal women showed significantly higher tau-PET signal in parieto-occipital regions (p < 0.0001). By contrast, no differences in tau-PET signal existed between pre-menopausal women and men. Aβ-PET was not associated with menopausal status or age. Neither Aβ-PET nor APOEε4 status moderated sex or menopause associations with tau-PET. Interpretation Clear divergence in tauopathy between the sexes are apparent approximately 20 years earlier than previously reported. Menopause status moderated sex differences in Aβ and tau-PET burden, with tau first appearing post-menopause. Sex and menopause differences consistently appeared in middle frontal and parieto-occipital regions but were not moderated by Aβ burden or APOEε4, suggesting that menopause-related tau vulnerability may be independent of AD-related pathways. ANN NEUROL 2022;92:11-22.
Key findings
- Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men.
- We examined global Aβ-PET, and tau-PET signal in 5 regions identified a priori as demonstrating significant sex differences in older adults (in temporal, inferior parietal, middle frontal, and lateral occipital regions).
- Results Women exhibited higher tau-PET signal (p < 0.002), and global Aβ-PET (p = 0.010), than men in inferior parietal, rostral middle frontal, and lateral occipital regions.
- Compared with age-matched men, post-menopausal women showed significantly higher tau-PET signal in parieto-occipital regions (p < 0.0001).
- Aβ-PET was not associated with menopausal status or age.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2022 — within 6 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35471588) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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APA 7th
Buckley, R. F., O'Donnell, A., McGrath, E. R., Jacobs, H. I. L., Lois, C., Satizabal, C. L., et al. (2022). Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study. Annals of neurology. https://doi.org/10.1002/ana.26382
Vancouver
Buckley RF, O'Donnell A, McGrath ER, Jacobs HIL, Lois C, Satizabal CL, et al. Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study. Annals of neurology. 2022. doi:10.1002/ana.26382. PMID: 35471588.
BibTeX
@article{buckley2022-35471588,
author = {Buckley, R. F. and O'Donnell, A. and McGrath, E. R. and Jacobs, H. I. L. and Lois, C. and Satizabal, C. L. and Ghosh, S. and Rubinstein, Z. B. and others},
title = {{Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study}},
journal = {Annals of neurology},
year = {2022},
doi = {10.1002/ana.26382},
pmid = {35471588},
url = {https://doi.org/10.1002/ana.26382}
}
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