Association of Metabolic Syndrome With Incident Dementia: Role of Number and Age at Measurement of Components in a 28-Year Follow-up of the Whitehall II Cohort Study

Abstract

Objective: Previous research suggests an inconsistent association between Metabolic syndrome (MetS) and incident dementia. We examined the role of number of MetS components and age at their assessment for incident dementia.

Research design and methods: MetS components (fasting glucose, triglycerides, waist circumference, blood pressure, and HDL cholesterol) on 7,265, 6,660, and 3,608 participants at <60, 60 to <70, and ≥70 years of age were used to examine associations with incident dementia using cause-specific Cox regression.

Results: Analyses of MetS measured at <60, 60 to <70, and ≥70 years involved 393 (5.4%), 497 (7.5%), and 284 (7.9%) dementia cases over a median follow-up of 20.8, 10.4, and 4.2 years, respectively. Every additional MetS component before 60 (hazard ratio [HR] 1.13 [95% CI 1.05, 1.23]) and 60 to <70 (HR 1.08 [95% CI 1.00, 1.16]) but not ≥70 years (HR 1.04 [95% CI 0.96, 1.13]) was associated with higher dementia risk. MetS defined conventionally (≥3 components) before 60 years (HR 1.23 [95% CI 0.96, 1.57]), between 60 and 70 years (HR 1.14 [95% CI 0.91, 1.42]), or >70 years of age (HR 1.10 [95% CI 0.86, 1.40]) was not associated with incident dementia. Multistate models showed higher risk of dementia in those with ≥1 (HR 1.99 [95% CI 1.08, 3.66]) and ≥2 MetS components (HR 1.69 [95% CI 1.12, 2.56]) before 60 years of age, even when they remained free of cardiovascular disease over the follow-up.

Conclusions: Risk of incident dementia increases with every additional MetS component present in midlife rather than after accumulation of three components; only part of this risk is mediated by cardiovascular disease.

Figure 1

Role of high metabolic risk (defined as presence of ≥1, ≥2, or ≥3 MetS components) at <60 years of age in the transition from: healthy state to incident CVD (stroke, CHD, or heart failure) (A); CVD (stroke, CHD, or heart failure) to incident dementia (B); and healthy state to incident dementia in those free of CVD (stroke, CHD, or heart failure) over the follow-up (C). Analyses with age as timescale and adjusted for sex, education, ethnicity, birth cohort (5 year groups), and health-related behaviors at <60 years of age (smoking, alcohol consumption, consumption of fruits and vegetables, and physical activity).