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. 2025 Jul;21(7):e70506.
doi: 10.1002/alz.70506.

Sex differences in modifiable dementia risk factors: Findings from the Rush Memory and Aging Project

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Sex differences in modifiable dementia risk factors: Findings from the Rush Memory and Aging Project

Jissa Martin et al. Alzheimers Dement. 2025 Jul.

Abstract

Introduction: We aimed to calculate population attributable fractions (PAFs) for incident dementia and examine sex differences in individuals with no cognitive impairment (NCI) or mild cognitive impairment (MCI).

Methods: Longitudinal data from the Rush University Memory and Aging Project (MAP) were analyzed. Cox proportional-hazards models were used to estimate covariate-adjusted hazard ratios for incident dementia and calculate weighted PAFs within each cognitive status/sex subgroup.

Results: The analytical sample comprised 1481 NCI (76.7% female) and 515 MCI (69.7% female) participants. Overall PAFs were similar for NCI (18.2%) and MCI (18.6%) subgroups, however, sex differences were evident. Males had higher PAFs than females in both NCI (42.5% vs. 25.1%) and MCI (51.5% vs. 12.4%), with differing risk factor profiles.

Discussion: These findings support the notion that dementia risk is modifiable after the onset of MCI and that the number of potentially preventable dementia cases may be higher in males than in females.

Highlights: The proportion of potentially preventable dementia cases was similar for no cognitive impairment (NCI) and mild cognitive impairment (MCI) individuals. For both cognitive states, a higher proportion of potentially preventable dementia cases was observed in males compared to females. The profiles of modifiable risk factors contributing to dementia differed between males and females. Lifestyle related risk factors were more prominent contributors to preventable dementia in males. Psychosocial risk factors, such as depression and social isolation, were important contributors in females.

Keywords: dementia; mild cognitive impairment; modifiable risk factors; population attributable fractions; sex differences.

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Conflict of interest statement

The authors have no conflicts of interest to report. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Flowchart of study participant selection. MAP, Memory and Aging Project.
FIGURE 2
FIGURE 2
PAFs for modifiable dementia risk factors in males and females with no cognitive impairment. Outer circles represent the prevalence of each risk factor with larger, darker circles denoting higher prevalence. Gray lines connecting each outer circle to its corresponding inner circle indicate the hazard ratio for dementia. Inner circles represent the individual PAF for each factor with size proportional to PAF magnitude. PAF, population attributable fraction.
FIGURE 3
FIGURE 3
PAFs for modifiable dementia risk factors in males and females with mild cognitive impairment. Outer circles represent the prevalence of each risk factor with larger, darker circles denoting higher prevalence. Gray lines connecting each outer circle to its corresponding inner circle indicate the hazard ratio for dementia. Inner circles represent the individual PAF for each factor with size proportional to PAF magnitude. PAF, population attributable fraction; TBI, traumatic brain injury.

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