Obesity phenotypes in midlife and cognition in early old age The Whitehall II cohort study

Objective: To examine the association of body mass index (BMI) and metabolic status with cognitive function and decline. Methods: A total of 6,401 adults (71.2% men), aged 39-63 years in 1991-1993, provided data on BMI (normal weight 18.5-24.9 kg/m(2), overweight 25-29.9 kg/m(2); and obese >= 30 kg/m(2)) and metabolic status (abnormality defined as 2 or more of 1) triglycerides >= 1.69 mmol/L or lipid-lowering drugs, 2) systolic blood pressure >= 130 mm Hg, diastolic blood pressure >= 85 mm Hg, or antihypertensive drugs, 3) glucose >= 5.6 mmol/L or medications for diabetes, and 4) high-density lipoprotein cholesterol <1.04 mmol/L for men and <1.29 mmol/L for women). Four cognitive tests (memory, reasoning, semantic, and phonemic fluency) were administered in 1997-1999, 2002-2004, and 2007-2009, standardized to z scores, and averaged to yield a global score. Results: Of the participants, 31.0% had metabolic abnormalities, 52.7% were normal weight, 38.2% were overweight, and 9.1% were obese. Among the obese, the global cognitive score at baseline (p = 0.82) and decline (p = 0.19) over 10 years was similar in the metabolically normal and abnormal groups. In the metabolically normal group, the 10-year decline in the global cognitive score was similar (p for trend = 0.36) in the normal weight (-0.40; 95% confidence interval [ CI] - 0.42 to -0.38), overweight (-0.42; 95% CI -0.45 to -0.39), and obese (-0.42; 95% CI -0.50 to -0.34) groups. However, in the metabolically abnormal group, the decline on the global score was faster among obese (-0.49; 95% CI -0.55 to -0.42) than among normal weight individuals (-0.42; 95% CI -0.50 to -0.34), (p = 0.03). Conclusions: In these analyses the fastest cognitive decline was observed in those with both obesity and metabolic abnormality. Neurology (R) 2012;79:755-762