The association of age at diagnosis of hypertension with brain structure and incident dementia in the UK Biobank

Little is known about whether the association of hypertension with brain volume and dementia is modified by an individual's age at their diagnosis of hypertension. Our analysis was based on the UK Biobank with baseline data collected between 2006 and 2010. Brain magnetic resonance imaging was used to measure brain volumes between 2014 and 2019. Dementia was ascertained using hospital inpatient, mortality, and self-reported data until 2021. We randomly selected a control participant for each hypertensive participant stratified by hypertension diagnosis age using propensity score. The cohort comprised 11 399 individuals with hypertension and 11 399 controls for the brain volume analysis and 124 053 individuals with hypertension and 124 053 controls for the dementia analysis. Individuals with hypertension diagnosed at ages <35 (beta (95% CI, -10.83 [-19.27 to -2.39] mL), 35 to 44 (-6.82 [-12.18 to -1.46] mL), and 45 to 54 years (-3.77 [-6.91 to -0.64] mL) had smaller total brain volume compared with the corresponding controls in the multivariable analysis. Similarly, hypertension diagnosed in early- and mid-life was independently associated with smaller volumes of gray matter, peripheral cortical gray matter, and white matter. Over a median follow-up of 11.9 years, 4626 cases of incident all-cause dementia were documented. Individuals with hypertension diagnosed at 35 to 44 years of age only (hazard ratio [95% CI]: 1.61 [1.31-1.99]) had a higher risk of all-cause dementia compared with the corresponding controls after adjustment for covariates. Hypertension diagnosed in young adulthood or mid-life, but not late life is associated with smaller brain volumes and an increased risk of dementia.