Sex Differences in Domain-Specific Cognitive Trajectories and Dementia Risk: Evidence From the Whitehall II Cohort.
5 affiliations
- 1Ageing Epidemiology (AGE) Research Unit School of Public Health Imperial College London London UK imperial.ac.uk.
- 2Surgery and Cancer Imperial College London London UK imperial.ac.uk.
- 3Division of Clinical Geriatrics Center for Alzheimer Research Karolinska Institutet and Karolinska University Hospital Stockholm Sweden ki.se.
- 4Imperial Clinical Trials Unit School of Public Health Imperial College London London UK imperial.ac.uk.
- 5Department of Epidemiology and Biostatistics MRC Centre for Environment and Health School of Public Health, Imperial College London London UK.
Abstract
Background
Evidence on sex differences in cognition and dementia is inconsistent, and it is unclear whether such differences are explained by dementia risk factors.Objective
To assess (i) sex differences in cognitive decline and dementia risk, (ii) the extent to which modifiable and nonmodifiable risk factors explain these differences and (iii) whether birth cohort and apolipoprotein (APOE)-Ꜫ4 carrier status modify sex differences in cognitive decline.Methods
Data from the Whitehall II study were analysed to examine cross-sectional and longitudinal associations between sex, cognitive decline and dementia risk. Cognitive outcomes included verbal memory and verbal fluency, assessed from Phase 5 onward, with over 16 years of follow-up. Test scores were standardised using means and standard deviations from the baseline cognitive tests to generate z-scores. All-cause dementia was ascertained through linkage to three electronic health record databases.Results
Among 5920 participants aged 44.8-68.2 years, women demonstrated better baseline performance than men in memory (adjusted mean difference = -0.2, p < 0.0001), phonemic fluency (-0.1, p = 0.001) and semantic fluency (-0.2, p < 0.0001). Men exhibited a steeper decline in semantic fluency (adjusted β = -2.6, p < 0.0001) and a nominal decline in phonemic fluency (-1.7, p = 0.007). Sex differences remained after adjustment for covariates. Dementia incidence did not differ significantly by sex. Birth cohort and APOE-Ꜫ4 carrier status did not meaningfully modify associations between sex and cognitive outcomes.Conclusion
Cognitive advantages observed in women in midlife did not translate into lower dementia risk. Further research incorporating biological, psychosocial and life-course factors, as well as the timing and heterogeneity of underlying disease processes, is needed to better understand sex differences in cognitive ageing and dementia.
Related
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- Mini‐Mental State Examination trajectories across dementia subtypes in the Swedish Registry for Cognitive/Dementia Disorders and U.S. National Alzheimer's Coordinating Center
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- Cognitive Trajectories of Post-Stroke Delirium: Longitudinal Global and Domain-Specific Impairment and Digital Markers
- Home-administered unfocused transcranial ultrasound in subjective cognitive decline and dementia: an open-label, uncontrolled feasibility pilot study
BibTeX
@article{toopchiani2026differences,
title = {{Sex Differences in Domain-Specific Cognitive Trajectories and Dementia Risk: Evidence From the Whitehall II Cohort.}},
author = {Sima Toopchiani and Shireen Sindi and Leila Janani and Oliver Robinson},
journal = {Journal of aging research},
year = {2026},
month = oct,
doi = {10.1155/jare/1953393},
url = {https://europepmc.org/article/MED/42959399},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sex Differences in Domain-Specific Cognitive Trajectories and Dementia Risk: Evidence From the Whitehall II Cohort.
AU - Sima Toopchiani
AU - Shireen Sindi
AU - Leila Janani
AU - Oliver Robinson
PY - 2026
DA - 2026/10/28
JO - Journal of aging research
DO - 10.1155/jare/1953393
UR - https://europepmc.org/article/MED/42959399
AB - Background Evidence on sex differences in cognition and dementia is inconsistent, and it is unclear whether such differences are explained by dementia risk factors.Objective To assess (i) sex differences in cognitive decline and dementia risk, (ii) the extent to which modifiable and nonmodifiable risk factors explain these differences and (iii) whether birth cohort and apolipoprotein (APOE)-Ꜫ4 carrier status modify sex differences in cognitive decline.Methods Data from the Whitehall II study were analysed to examine cross-sectional and longitudinal associations between sex, cognitive decline and dementia risk. Cognitive outcomes included verbal memory and verbal fluency, assessed from Phase 5 onward, with over 16 years of follow-up. Test scores were standardised using means and standard deviations from the baseline cognitive tests to generate z-scores. All-cause dementia was ascertained through linkage to three electronic health record databases.Results Among 5920 participants aged 44.8-68.2 years, women demonstrated better baseline performance than men in memory (adjusted mean difference = -0.2, p < 0.0001), phonemic fluency (-0.1, p = 0.001) and semantic fluency (-0.2, p < 0.0001). Men exhibited a steeper decline in semantic fluency (adjusted β = -2.6, p < 0.0001) and a nominal decline in phonemic fluency (-1.7, p = 0.007). Sex differences remained after adjustment for covariates. Dementia incidence did not differ significantly by sex. Birth cohort and APOE-Ꜫ4 carrier status did not meaningfully modify associations between sex and cognitive outcomes.Conclusion Cognitive advantages observed in women in midlife did not translate into lower dementia risk. Further research incorporating biological, psychosocial and life-course factors, as well as the timing and heterogeneity of underlying disease processes, is needed to better understand sex differences in cognitive ageing and dementia.
SN - 2090-2204
SN - 2090-2212
ER -