A large-scale cohort study in Japan found that individuals whose spouses experienced cardiovascular disease events faced a higher risk of developing dementia.
In a large-scale cohort study in Japan, published in JAMA Neurology, investigators used the data of 93,396 individuals enrolled in the Japan Health Insurance Association insurance program to examine the interpersonal pathway for elevated dementia risk, potentially revealing new avenues for monitoring and early intervention strategies.
The study covered the period from April 1, 2016, to March 31, 2022. The Kyoto University institutional review board approved the study with a waiver of informed consent due to the retrospective nature of the data. The study followed the STROBE reporting guideline for observational studies.
The study employed a target trial emulation framework to adjust for potential confounders. Index individuals who were dementia free at baseline were matched with comparison individuals whose spouses had not experienced cardiovascular disease (CVD). Matching criteria included age, sex, and income. The median follow-up period was 24 months (interquartile range = 10–42 months).
The investigators used multivariable Poisson regression models to explore the association between spouses' CVD and individuals' dementia. Models were adjusted for age, sex, spouse's age, income, and disease histories of both index individuals and spouses (including diabetes, hypertension, CVD, and dementia). The cumulative incidence function accounted for death of index individuals. Statistical analysis was performed using R version 4.3.0.
The investigators found that individuals aged 65 years or older whose spouses experienced CVD events faced a 32% higher incidence rate of dementia compared with matched controls (incidence rate ratio [IRR] = 1.32, 95% confidence interval [CI] = 1.10–1.57).
Among the key findings were:
- Demographics: Mean age of index individuals was 68.8 (SD = 2.6) years, 96.2% were men, and 3.8% were women
- Outcomes: 559 dementia events and 1,653 deaths occurred among index individuals during follow-up period
- Cumulative incidence: Exposed group (those with spouses who had CVD events) showed higher cumulative incidence of dementia compared with unexposed group
- Disease history prevalence: 39.6% of index individuals had history of diabetes, 57.9% had hypertension, and 19.1% had CVD.
The investigators conducted subgroup analyses to examine potential heterogeneity in associations:
- Male subgroup IRR = 1.33 (95% CI = 1.11–1.59)
- Female subgroup IRR = 0.78 (95% CI = 0.26–2.38)
- Diabetes history subgroup IRR = 1.37 (95% CI = 1.06–1.76)
- No diabetes history subgroup IRR = 1.26 (95% CI = 0.99–1.61)
- Hypertension history subgroup IRR = 1.18 (95% CI = 0.95–1.46)
- No hypertension history subgroup IRR = 1.61 (95% CI = 1.19–2.17)
- CVD history subgroup IRR = 1.49 (95% CI = 1.08–2.05)
- No CVD history subgroup IRR = 1.24 (95% CI = 1.01–1.53).
The study had several limitations, including a short follow-up period, uncontrolled confounders, potential measurement errors, a lack of detailed socioeconomic data, and a predominantly male population, limiting generalizability.
The study was supported by grants from the Japan Health Insurance Association, with additional funding from various Japanese research agencies. The research was conducted against the backdrop of a projected global dementia prevalence of 152.8 million patients by 2050.
Conflict of interest disclosures can be found in the study.
