Age, sex, and APOE gene-specific associations between dynapenic obesity and dementia in a large cohort.

Objective: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort.

Methods: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses.

Results: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44-1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65-2.50), younger (<65 years, HR: 1.97, 95% CI: 1.55-2.50), and non-ε4-carrier (HR: 1.97, 95% CI: 1.60-2.44) (all P for interaction <0.05). In participants under 65 years and non-ε4-carrier, those with dynapenic obesity had the highest risk of dementia (HR: 2.63, 95% CI: 1.91-3.62), compared with the healthy group (P for second order interaction = 0.026).

Conclusions: Dynapenic obesity is associated with increased risks of dementia, especially in participants under 65 years and non-ε4-carrier, suggesting the importance of managing dynapenic obesity in the prevention of cognition-related disorders.