Methods: Participants were 4,323 women and 2,764 men aged 65 and over enrolled in the longitudinal Three-City Study. Cognitive decline, defined as being in the worst quintile of the distribution of the difference between baseline score and either 2- or 4-year follow-up, was assessed by the Mini-Mental State Examination (MMSE, global cognitive function), the Isaacs Set Test (IST, verbal fluency), and the Benton Visual Retention Test (BVRT, visual working memory). MetS was defined by National Cholesterol Education Program–Adult Treatment Panel III criteria (at least 3 of 5 cardio-metabolic abnormalities: hypertension, high waist circumference, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, hyperglycemia). Proportional hazards models were adjusted for age, gender, educational level, center, baseline cognitive score, APOE4 genotype, and other potential confounders.

Results: MetS at baseline was associated with an increased risk of cognitive decline on MMSE (hazard ratio [HR] = 1.22 [1.08–1.37]; p = 0.001) and BVRT (HR = 1.13 [1.01–1.26]; p = 0.03) but not on IST (HR = 1.11 [0.95–1.29]; p = 0.18). Among MetS components, hypertriglyceridemia and low HDL cholesterol were significantly associated with higher decline on MMSE; diabetes, but not elevated fasting glycemia, was significantly associated with higher decline on BVRT and IST.

Conclusions: MetS as a whole and several of its components had a negative impact on global cognitive decline and specific cognitive functions in older persons.

Footnotes
Study funding: The 3C Study is conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut de Santé Publique et Développement (ISPED) of the Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l'Education Nationale, Institut de la Longévité, Regional Councils of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques.” The Lille Genopole was supported by an unconditional grant from Eisai. Mélanie Le Goff worked with the financial support of the “ANR–Agence Nationale de la Recherche–The French National Research Agency” under the “Programme National de Recherche en Alimentation et Nutrition Humaine,” project COGINUT ANR-06-PNRA-005.