Neurology. 2025 May 27;104(10):e213599. doi: 10.1212/WNL.0000000000213599. Epub 2025 Apr 23.
ABSTRACT
BACKGROUND AND OBJECTIVES: Young-onset dementia (YOD) poses substantial societal and health care burdens. Although metabolic syndrome (MetS) is recognized as a contributor to late-onset dementia, its effect on YOD remains unclear. This study aimed to determine whether MetS and its individual components increase the risk of YOD, including all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD).
METHODS: We conducted a nationwide population-based cohort study using data from the Korean National Insurance Service. Individuals aged 40-60 who underwent national health check-ups in 2009 were included and followed until December 31, 2020, or age 65, whichever came first. MetS was defined according to established guidelines, incorporating measurements of waist circumference, blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Covariates included age, sex, income level, smoking status, alcohol consumption, and comorbidities such as hypertension, diabetes, dyslipidemia, and depression. The primary outcome was incident all-cause YOD, defined as a dementia diagnosis before age 65; secondary outcomes included young-onset AD and VaD. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs.
RESULTS: A total of 1,979,509 participants (mean age, 49.0 years; 51.3% men; 50.7% with MetS) were included. Over an average follow-up of 7.75 years, 8,921 individuals (0.45%) developed YOD. MetS was associated with a 24% higher risk of all-cause YOD (adjusted HR 1.24, 95% CI 1.19-1.30), a 12.4% increased risk of AD (HR 1.12, 95% CI 1.03-1.22), and a 20.9% increased risk of VaD (HR 1.21, 95% CI 1.08-1.35). Significant interactions were noted with younger age (40-49 vs 50-59), female sex, drinking status, obesity, and depression.
DISCUSSION: In this large Korean cohort, MetS and its individual components were significantly associated with an increased risk of YOD. These findings suggest that interventions targeting MetS may help mitigate YOD risk. However, the observational design precludes definitive causal inferences, and reliance on claims data could introduce misclassification bias. Future research using longitudinal designs and comprehensive data collection is needed to validate and expand on these associations.
PMID:40267374 | DOI:10.1212/WNL.0000000000213599
