Evidence map›Paper›PMID 40043118›Full record

ArticleScience advances2025

The interplay between age at menopause and synaptic integrity on Alzheimer's disease risk in women.

Madeline Wood Alexander, William G Honer, Rowan Saloner, Liisa A M Galea, David A Bennett, Jennifer S Rabin, Kaitlin B Casaletto

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Elevated temporal tau PET predicts faster cognitive decline in women than men: A meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Pooled it
  2. Trial
  3. Article
  4. Observational
  5. Article
  6. Menopausal insomnia as a modifiable node of dementia risk: Mechanistic insights and intervention strategies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  7. Article
  8. Age at menopause,Research square · 2026
    Article
  9. Article
  10. Plasma proteomics link menopause timing to brain aging and dementia risk.medRxiv : the preprint server for health sciences · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  15. Neurologic Complications of Pregnancy and Menopause.Continuum (Minneapolis, Minn.) · 2026
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Madeline Wood AlexanderHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.ORCID 0000-0003-4598-0201
William G HonerDepartment of Psychiatry, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-7628-5108
Rowan SalonerMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID 0000-0002-1351-6183
Liisa A M GaleaDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0003-2874-9972
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.ORCID 0000-0003-3689-554X
Jennifer S RabinHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.ORCID 0000-0003-4754-2221
Kaitlin B CasalettoMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID 0000-0001-5000-7604

Funding

EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Unraveling the intersection of synaptic biology, lifestyle, and cognitive resilienceR01AG072475 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CASALETTO, KAITLIN B · 2021 to 2025
$4.3M
Leveraging mouse and human models to investigate neuroprotective effects of blood-derived exerkines in Alzheimer's diseaseR56AG082414 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CASALETTO, KAITLIN B, VILLEDA, SAUL A · 2023 to 2023
$1.2M
NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG072475NIA NIH HHS R56 AG082414
6 · The paper itself

Abstract

Menopause is a major biological transition that may influence women's late-life brain health. Earlier estrogen depletion-via earlier menopause-has been associated with increased risk for Alzheimer's disease (AD). Synaptic dysfunction also incites and exacerbates AD progression. We investigated whether age at menopause and synaptic health together influence AD neuropathology and cognitive trajectories using clinical and autopsy data from 268 female decedents in the Rush Memory and Aging Project. We observed significant interactions between age at menopause and synaptic integrity on cognitive decline and tau tangles, such that earlier menopause strengthened the associations of reduced synaptic integrity with faster cognitive decline and elevated tau. Exploratory analyses showed that these relationships were attenuated in women who took menopausal hormone therapy. These findings suggest that midlife endocrine processes or their sequalae may influence synaptic vulnerability to AD. Interventions addressing both hormonal factors and synaptic health could enhance resilience to dementia in women.

Indexed as

Alzheimer DiseaseMenopauseSynapsesAgedAged, 80 and overAge FactorsAgingCognitive DysfunctionFemaleHumansMiddle AgedRisk Factorstau Proteinstau Proteins

Identifiers

PMID40043118
PMCPMC11881898

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.