Obesity, metabolic health, and brain health: Insights from a prospective cohort study.

Background: Metabolically healthy obesity (MHO) has been linked to an increased risk of cardiovascular disease, but its link to neurological and mental health remains unclear. This cohort study explored associations between metabolic-obesity phenotypes and multiple brain-related disorders.

Methods: This population-based prospective cohort study included 318,103 UK Biobank participants with a median follow-up of 13.2 years. MHO was defined as BMI ≥ 30 kg/m and at least four of six metabolic biomarkers. Outcomes included stroke, anxiety, depression, bipolar disorder, dementia, and Parkinson's disease (PD) that were defined by ICD-10 codes. Cox regression models were performed to examine associations of metabolic-obesity phenotypes with neurological and mental disorders.

Results: Compared to metabolically healthy non-obesity (MHN) individuals, MHO participants had significantly elevated risks of stroke (HR, 1.11; 95 % CI: 1.03-1.20), anxiety (HR, 1.16; 95 % CI: 1.08-1.23), and depression (HR, 1.43; 95 % CI: 1.34-1.52). Elevated stroke risks were also observed in metabolically unhealthy non-obese (MUN) and metabolically unhealthy obese (MUO) groups. Similar patterns were found for anxiety and depression. Furthermore, stratified analyses showed significantly increased dementia risk in MUN (HR, 1.35; 95 % CI: 1.18-1.55) and MUO (HR, 1.27; 95 % CI: 1.10-1.47) among participants aged under 65, but not in older individuals.

Conclusions: The study found that MHO and MUO are significantly associated with elevated risks of brain-related disorders, including stroke, anxiety, and depression, while dementia risk is more likely linked to metabolically unhealthy states, irrespective of obesity. These findings highlight the importance of both metabolic health and normal weight to improve brain health.