Association of birth weight, midlife obesity, and transition patterns with mild cognitive impairment and brain MRI...

To evaluate associations of birth weight, midlife weight, and their transitions with mild cognitive impairment (MCI) and brain MRI indices.

This prospective cohort study included 200,726 UK Biobank participants. Self-reported birth weight and measured midlife anthropometrics were used to classify obesity (waist circumference [WC]/waist-to-hip ratio [WHR]). We constructed nine weight transition patterns from birth to midlife WC, six from birth to midlife WHR. Cox proportional hazards models and linear regression models were used to examine associations of birth weight, midlife body size and their transitions with MCI and brain MRI indices.

Compared to normal birth weight, low birth weight (HR: 1.29, 95 % CI: 1.16-1.44) and high birth weight (1.11, 1.01-1.22) were both associated with increased risk of MCI, showing a U-shaped relationship. Compared to normal weight at midlife, midlife central obesity [WC (1.25, 1.15-1.37) and WHR (1.27, 1.17-1.37)] were significantly associated with elevated MCI risk. Compared to individuals with normal weight at birth and midlife, those with low birth weight who transition to central obesity at midlife, defined by WC (1.51, 1.27-1.78) or WHR (1.42, 1.22-1.66), showed the highest risk of MCI. Weight transitions were also associated with brain structure, individuals who had low or high birth weight and developed midlife obesity showed significant reductions in total brain volume and grey matter volume, as well as increases in white matter hyperintensity volume.

Birth weight exhibited a U-shaped association with MCI risk. Individuals transitioning from low birth weight to midlife central obesity demonstrated the highest MCI susceptibility.