Sex- and age-specific impacts of smoking, overweight/obesity, hypertension, and diabetes mellitus in the development of disabling dementia in a Japanese population

Sex- and age-specific impacts of cardiovascular risk factors on the development of dementia have not been well evaluated. We investigated these impacts of smoking, overweight/obesity, hypertension, and diabetes mellitus on the risk of disabling dementia. The study participants were 25,029 (10,134 men and 14,895 women) Japanese aged 40-74 years without disabling dementia at baseline (2008-2013). They were assessed on smoking status (non-current or current), overweight/obesity (body mass index ≥25 kg/m and ≥30 kg/m , respectively), hypertension (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or any antihypertensive medication use), and diabetes mellitus (a fasting serum glucose ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, hemoglobin A1c ≥6.5% by the National Glycohemoglobin Standardization Program or glucose-lowering medication use) at baseline. Disabling dementia was identified as the level of care required ≥1 and cognitive disability grade ≥IIa according to the National Long-term Care Insurance Database. We used a Cox proportional regression model to estimate hazard ratios and 95% confidence intervals (95% CIs) of disabling dementia according to the cardiovascular risk factors and calculated the population attributable fractions (PAFs). During a median follow-up of 9.1 years, 1,322 (606 men and 716 women) developed disabling dementia. Current smoking and hypertension were associated with a higher risk of disabling dementia in both sexes, whereas overweight or obesity was not associated with the risk in either sex. Diabetes mellitus was associated with a higher risk only in women (p for sex interaction = 0.04). The significant PAFs were 13% for smoking and 14% for hypertension in men and 3% for smoking, 12% for hypertension, and 5% for diabetes mellitus in women. The total PAFs of the significant risk factors were 28% in men and 20% in women. When stratified by age, hypertension in midlife (40-64 years) was associated with the increased risk in men, while diabetes mellitus in later-life (65-74 years) was so in women. A substantial burden of disabling dementia was attributable to smoking, and hypertension in both sexes and diabetes mellitus in women, which may require the management of these cardiovascular risk factors to prevent dementia.