Evidence map›Paper›PMID 40646704›Full record

ArticleAnnals of neurology2025

Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline.

Madeline Wood Alexander, D Luke Fischer, Lawren VandeVrede, Emma Nichols, Lei Yu, James R Pike, Walter Swardfager, Che-Yuan Wu, Mario Masellis, Liisa A M Galea and 8 more

Abstract read
In one paragraph

Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Age at menopause,Research square · 2026
    Article
  4. Article
  5. Plasma proteomics link menopause timing to brain aging and dementia risk.medRxiv : the preprint server for health sciences · 2026
    Article
  6. 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

18 authors.

Madeline Wood AlexanderHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.ORCID 0000-0003-4598-0201
D Luke FischerMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID 0000-0002-5245-3832
Lawren VandeVredeMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Emma NicholsCenter for Economic and Social Research and Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Lei YuRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.ORCID 0000-0002-0237-8758
James R PikeUniversity of North Carolina Gillings School of Public Health, Chapel Hill, NC, USA.
Walter SwardfagerHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.ORCID 0000-0002-0030-8908
Che-Yuan WuHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
Mario MasellisHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
Liisa A M GaleaDepartment of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
Katherine ZukotynskiHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
Gillian EinsteinDalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Sandra E BlackHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
Lisa L BarnesRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Zoe ArvanitakisRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
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
Jennifer S RabinHurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.ORCID 0000-0003-4754-2221

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
National Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Gil Dan Rabinovici · 2019 to 2026
$36.9M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Mark W Bondi · 2019 to 2026
$34.9M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin · 2019 to 2026
$34.5M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2019 to 2026
$33.5M
Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carolyn Wei Zhu · 2020 to 2026
$31.0M
Yale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER, CHRISTOPHER H VAN DYCK · 2020 to 2026
$30.2M
Research Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Miguel Arce · 2020 to 2026
$30.1M
Research Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI C. Elizabeth Shaaban · 2020 to 2026
$29.4M
Alzheimer's Association 1144933National Institute on Aging/National Institutes of Health and R01AG022018National Institute on Aging/National Institutes of Health P30AG010161National Institute on Aging/National Institutes of Health P30AG072975National Institute on Aging/National Institutes of Health R01AG017917NIA NIH HHS P20 AG068024NIA NIH HHS P20 AG068053NIA NIH HHS P20 AG068077NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG079280NIA NIH HHS U24 AG072122NINDS NIH HHS UE5 NS070680
6 · The paper itself

Abstract

objectiveTo investigate how sex and age at menopause influence the interplay between Alzheimer's disease (AD) and Lewy body disease (LBD) neuropathologies, and their associations with cognitive decline.

methodsWe analyzed data from: (1) three Rush Alzheimer's Disease Center cohorts (i.e., the Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study), and (2) the National Alzheimer's Coordinating Center Neuropathology Data Set. Neuropathological evaluation assessed LBD (neocortical/limbic-type vs none) and AD, including neuritic plaques (β-amyloid plaques surrounded by dystrophic neurites) and neurofibrillary tangles. In each dataset, we tested interactive associations between LBD and sex on neuritic plaques, neurofibrillary tangles, and cognitive decline. Additionally, in the Rush dataset, we tested whether age at spontaneous menopause modified the associations of LBD with neuritic plaques, neurofibrillary tangles, and cognitive decline in women.

resultsIn the Rush dataset, we included 1,277 women and 579 men. In the National Alzheimer's Coordinating Center dataset, we included 3,283 women and 3,563 men. Across both datasets, men were more likely to have LBD, whereas women showed greater neuritic plaque and neurofibrillary tangle burdens. Sex modified the associations of LBD with neurofibrillary tangles (but not neuritic plaques), whereby LBD was more strongly associated with greater neurofibrillary tangle burden in women than men. Men showed faster LBD-related cognitive decline, whereas women showed faster neurofibrillary tangle-related decline, after adjusting for copathologies (neuritic plaques, neurofibrillary tangles, and LBD, as appropriate). In women, earlier age at menopause exacerbated the associations of LBD with neurofibrillary tangle burden and episodic memory decline.

interpretationSex may influence AD and LBD neuropathologies, highlighting the need for precision approaches to dementia prevention and intervention. ANN NEUROL 2025;98:1014-1026.

Indexed as

Alzheimer DiseaseCognitive DysfunctionLewy Body DiseaseSex CharacteristicsAgedAged, 80 and overCohort StudiesFemaleHumansMaleMenopauseMiddle AgedNeurofibrillary TanglesPlaque, Amyloid

Identifiers

PMID40646704
PMCPMC12341763

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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.