Metabolic heterogeneity of obesity and cognitive decline: A 14-year population-based longitudinal cohort study

BACKGROUND: Previous studies indicate that there is metabolic heterogeneity in obese individuals. How this metabolic heterogeneity affects multidimensional cognitive decline in middle-aged and older populations is scarcely explored. METHODS: Data were derived from 2004 to 2005 (Wave 2) through 2018-2019 (Wave 9) of the English Longitudinal Study of Ageing (ELSA). Cognitive assessments were conducted face-to-face during these waves, covering three cognitive functions: memory, executive function, and orientation. Participants were categorized into four phenotypes based on BMI and metabolic status: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHOO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obesity (MUOO). Linear mixed-effects models were used to examine associations with cognitive decline. RESULTS: A total of 6211 participants were included (mean age at baseline, 65.7 years; 55.3% female), with a median follow-up of 12 years. Compared with MHNW, global cognitive decline was considerably accelerated in MUNW (-0.017 SD/year, 95% CI: -0.030 to -0.004, P = 0.009) and MUOO (-0.010 SD/year, 95% CI: -0.018 to -0.002, P = 0.018), primarily in memory function. No acceleration was observed in MHOO. Age and depression were significant moderators (interaction P < 0.05). Weight loss from MHOO to MHNW was linked to faster cognitive decline (-0.048 SD/year, 95% CI: -0.077 to -0.019; P = 0.001). CONCLUSIONS: Metabolic unhealth, rather than obesity, is significantly associated with faster cognitive decline. Weight loss in MHOO may be accompanied by potential cognitive risks.