Evidence map›Paper›PMID 41273226›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Exploring sex-specific risk factors in cognitive decline: Insights into modifiable and non-modifiable determinants using a network analysis.

Brittany Intzandt, Joel Ramirez, Benjamin Lam, Mario Masellis, Gillian Einstein, Louis Bherer, Sandra E Black, PREVENT‐AD Research Group, ONDRI and CCNA Investigators

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Brittany IntzandtSchool of Kinesiology and Health Science, Centre for Integrative and Applied Neuroscience, York University, Toronto, Ontario, Canada.
Joel RamirezThe Dr. Sandra Black Centre for Brain Resilience and Recovery, Cognitive Neurology Research Unit, Hurvitz Brain Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
Benjamin LamThe Dr. Sandra Black Centre for Brain Resilience and Recovery, Cognitive Neurology Research Unit, Hurvitz Brain Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
Mario MasellisThe Dr. Sandra Black Centre for Brain Resilience and Recovery, Cognitive Neurology Research Unit, Hurvitz Brain Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
Gillian EinsteinRotman Research Institute, Baycrest Academy for Research and Education, Toronto, Ontario, Canada.
Louis BhererResearch Center and Centre ÉPIC, Montréal Heart Institute, Montreal, Quebec, Canada.
Sandra E BlackThe Dr. Sandra Black Centre for Brain Resilience and Recovery, Cognitive Neurology Research Unit, Hurvitz Brain Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
PREVENT‐AD Research Group
ONDRI and CCNA Investigators

Funding

Investigating the impact of loneliness on brain aging and pre-symptomatic Alzheimer's disease progressionR01AG068563 · NIA · MCGILL UNIVERSITY · PI BZDOK, DANILO, SPRENG, ROBERT NATHAN · 2020 to 2024
$2.3M
Alzheimer Society Research ProgramCanada Foundation for InnovationCIHR BDO-148341CIHR CIHR CNA-137794CIHR CNA-163902Douglas Hospital Research Centre and FoundationFondation Jean-Louis LévesqueFonds de Recherche du Québec - Santé FRQ-356162Foundation Brain CanadaMcGill UniversityNational Institute of Health of the United StatesNIA NIH HHS R01 AG068563Ontario Brain InstitutePfizer Canada
6 · The paper itself

Abstract

backgroundHow sex-specific risk factors for dementia interact remains understudied. Network analysis provides a novel approach to examine these relationships, offering insights into sex-specific risk factor connectivity in healthy controls (HCs) and individuals with mild cognitive impairment or Alzheimer's disease (cognitive decline [CD]).

methodsA network analysis of 896 participants examined associations among modifiable, non-modifiable, and cognitive risk factors. Network invariance and global strength tests assessed structural and connectivity differences.

resultsIn males, network invariance differed between HC and CD groups, but connectivity was unchanged. In females, network invariance and connectivity were significantly altered, with HC females exhibiting stronger overall connectivity. Key risk factors in females included systolic blood pressure and apolipoprotein E ε4, whereas males' networks were primarily influenced by cognitive outcomes. DISCUSSION: Sex-specific networks suggest distinct mechanisms underlying cognitive decline. Future work differentiating mild cognitive impairment and Alzheimer's disease stages will refine our understanding of risk factor evolution and inform precision medicine approaches to dementia prevention. HIGHLIGHTS: Sex-stratified networks of risk factors differ in healthy and cognitively impaired adults. Female networks show greater global connectivity in healthy versus cognitively decline groups. Apolipoprotein E, family history, and lifestyle factors show sex-specific centrality in networks. Network structure changes more in females across the cognitive decline spectrum. Findings support sex-specific modeling of dementia risk for precision prevention.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAgedApolipoprotein E4FemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsRisk FactorsSex FactorsApolipoprotein E4Alzheimer's diseasenetwork analysisrisk factorssex differences

Identifiers

PMID41273226
PMCPMC12639403

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.