Evidence mapPaperPMID 41211101Full record

ArticleImaging neuroscience (Cambridge, Mass.)2025

Investigating the impact of sex and reproductive aging on latent signatures of modifiable dementia risk factors.

Alice Mukora, Manuela Costantino, Olivier Parent, Gabriel A Devenyi, M Mallar Chakravarty

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Article in Imaging neuroscience (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Alice MukoraMcGill University-Integrated Program in Neuroscience, Montreal, QC, Canada.ORCID https://orcid.org/0000-0001-8431-985X
Manuela CostantinoUniversity of Chicago-Committee on Genetics, Genomics and Systems Biology, Chicago, IL, United States.
Olivier ParentMcGill University-Integrated Program in Neuroscience, Montreal, QC, Canada.
Gabriel A DevenyiCerebral Imaging Centre-Douglas Mental Health University Institute, Montreal, QC, Canada.
M Mallar ChakravartyMcGill University-Integrated Program in Neuroscience, Montreal, QC, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treating modifiable risk factors for dementia may serve to prevent maladaptive brain aging. These include, and are not limited to, obesity, hypertension, and other metabolic disorders. Nearly two-thirds of affected individuals are female, and emerging research has pointed to potential sex-specific factors, such as reproductive aging, as potent modifiers of dementia risk. Here, we leverage neuroimaging to characterize sex differences in the neural signatures of modifiable dementia risk factors, examining their relationship with brain anatomy, and integrate female-specific factors related to menopause history in a sex-specific analysis. Using cross-sectional data from the UK Biobank, we selected a cohort of 31,711 (age 44-82, 55.2% female/44.8% male) participants without diagnosed neurological conditions and collated behavioral data previously determined as modifiable risk factors. Using partial least squares analysis (PLS), we examined latent signatures that represent linear combinations that maximize covariance between patterns of brain (mean cortical thickness from 64 regions) and risk factor variables. To examine sex differences, we performed PLS analysis using the entire sample. We performed linear models to explore age-by-sex interactions with the PLS-derived brain scores and the risk factor pattern scores. To examine sex-specific relationships, we performed separate PLS analyses for the males and females and integrated menopause-related variables into the latter analysis. Our study found sex-dependent and menopause-dependent relationships between lifestyle risk factors and cortical thickness, highlighting stronger impacts of cardiometabolic factors on males and social and obesity-related factors on females in preserving brain health. The inclusion of menopause-related variables did not change the relationships with lifestyle risk factors, and strict age matching dampened the strength of the findings. Our findings suggest that lifestyles and the female-specific endocrine environment influence sex differences in cortical anatomy during brain aging.

Indexed as

agingmenopausepartial least squaressex differencesstructural MRI

Identifiers

PMID41211101
PMCPMC12592373

What Socratic holds

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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 Socratic graph.