What is the clinical evidence from this study?

Study design: Cohort. Population: Incident all-cause dementia (n=502226). Intervention: Female sex vs. Male sex. Primary outcome: Incident fatal or non-fatal all-cause dementia (HR 0.83, 95% CI 0.77-0.89).

May 19, 2021BMC Medicine123 citationsOpen Access

Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK Biobank

JGJessica GongThe George Institute for Global Health KHKatie HarrisUNSW Sydney SPSanne A. E. PetersPreventive Cardiology

Key Result

Women had a lower overall risk of incident dementia compared to men (HR 0.83), and raised systolic blood pressure increased dementia risk in women (HR 1.08 per 20 mmHg) but not in men.

Study Design

Type

Cohort (n=502,226)

Multicenter

Yes

Structured PICO

Population

502,226 individuals aged 40-69 without prevalent dementia at baseline, followed for a median of 11.8 years to assess sex differences in cardiovascular risk factors for incident dementia.

Outcome

Incident fatal or non-fatal all-cause dementiahard clinical

Midlife cardiovascular risk factors increase dementia risk similarly in men and women, except for elevated blood pressure, which shows a dose-response relationship with dementia risk in women but a U-shaped relationship in men.

Main Result

Hazard Ratio: 0.83 (95% CI 0.77–0.89)

Absolute Event Rate: 5.88% vs 8.42%

Limitations

The UK Biobank cohort is a relatively healthy and affluent population, predominantly of Caucasian ancestry, which may limit generalizability.
Self-reported smoking, diabetes, and history of stroke may be subject to reporting bias.
Multiple testing of interactions can raise the concern of false positives.
Lack of information on medication use duration or dose for antihypertensives limits interpretation.

Abstract

BACKGROUND: Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). METHODS: Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. RESULTS: 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 95% CI 5.62-6.16 for women and 8.42 8.07-8.78 for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 0.77-0.89). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 1.02-1.13 in women and 0.98 0.93-1.03 in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer's disease). CONCLUSIONS: Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.

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