Association of type 1 diabetes and age at diagnosis of type 2 diabetes with brain volume and risk of dementia in the UK Biobank: A prospective cohort study of community‐dwelling participants

To investigate the association of type 1 diabetes (T1D) and age at diagnosis of type 2 diabetes (T2D) with brain structure and incident dementia.Our analysis was based on the UK Biobank. We included 1376 participants with diabetes and 2752 randomly selected controls for brain volume analysis, and 25,141 participants with diabetes and 50,282 randomly selected controls for dementia analysis. Brain volume was measured using magnetic resonance imaging. Dementia was identified using hospital inpatient records and mortality register data until January 2021.T2D diagnosed at a younger age was associated with larger reductions in brain volume. After adjustment for glycated haemoglobin (HbA1c) and other covariates, only T2D diagnosed <50 years was associated with smaller total brain volume (β (95% CI): -14.56 (-24.67, -4.44) ml), and grey (-6.47[-12.75, -0.20] ml) and white matter volumes (-8.08[-14.66, -1.51] ml). Corresponding numbers for total brain, grey matter and white matter volumes associated with T1D were -62.86 (-93.71,-32.01), -34.27 (-53.72, -14.83), and -28.59 (-47.65, -9.52) ml, respectively. During a median follow-up of 11.9 years, 2035 new dementia cases were identified. Younger age at diagnosis of T2D was associated with larger excessive risk of dementia, whereas T2D diagnosed <50 years was associated with the largest hazard ratio (HR) (95% CI: 2.03[1.53-2.69]) in the multivariable analysis. The HR (95% CI) for dementia associated with T1D was 2.08 (1.40-3.09).Individuals with T1D or T2D diagnosed at younger age are at larger excessive risk of brain volume reduction and dementia.