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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

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posted on 2022-07-12, 15:08 authored by Marcos D. Machado-Fragua, Aurore Fayosse, Manasa Shanta Yerramalla, Thomas T. van Sloten, Adam G. Tabak, Mika Kivimaki, Séverine Sabia, Archana Singh-Manoux


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 7265, 6660, and 3608 participants at age <60, 60 to <70, and ≥70 years were used to examine associations with incident dementia using cause-specific Cox regression. 

Results, Analyses of MetS measured <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 (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 60-70 years (HR 1.14, 95%CI 0.91, 1.42), or after 70 years (HR 1.10, 95%CI 0.86, 1.40) was not associated with incident dementia. Multi-state models showed higher risk of dementia in those with 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 age 60, 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 3 components; only part of this risk is mediated by cardiovascular disease.


The Whitehall II study has been supported by grants from the National Institute on Aging, NIH (R01AG056477, R01AG062553); UK Medical Research Council (R024227, S011676), and the Wellcome Trust (221854/Z/20/Z). MK is supported by the Academy of Finland (311492), Helsinki Institute of Life Science, and NordForsk. SS is supported by the French National Research Agency (ANR-19-CE36-0004-01).


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