RESUMO
BACKGROUND: Elevated blood pressure (BP) is a modifiable risk factor associated with cognitive impairment and cerebrovascular diseases. However, the causal effect of BP on white matter brain aging remains unclear. METHODS: In this study, we focused on N â=â228â473 individuals of European ancestry who had genotype data and clinical BP measurements available (103â929 men and 124â544 women, mean ageâ=â56.49, including 16â901 participants with neuroimaging data available) collected from UK Biobank (UKB). We first established a machine learning model to compute the outcome variable brain age gap (BAG) based on white matter microstructure integrity measured by fractional anisotropy derived from diffusion tensor imaging data. We then performed a two-sample Mendelian randomization analysis to estimate the causal effect of BP on white matter BAG in the whole population and subgroups stratified by sex and age brackets using two nonoverlapping data sets. RESULTS: The hypertension group is on average 0.31âyears (95% CIâ=â0.13-0.49; P â<â0.0001) older in white matter brain age than the nonhypertension group. Women are on average 0.81âyears (95% CIâ=â0.68-0.95; P â<â0.0001) younger in white matter brain age than men. The Mendelian randomization analyses showed an overall significant positive causal effect of DBP on white matter BAG (0.37âyears/10âmmHg, 95% CI 0.034-0.71, P â=â0.0311). In stratified analysis, the causal effect was found most prominent among women aged 50-59 and aged 60-69. CONCLUSION: High BP can accelerate white matter brain aging among late middle-aged women, providing insights on planning effective control of BP for women in this age group.
Assuntos
Hipertensão , Substância Branca , Pessoa de Meia-Idade , Masculino , Humanos , Feminino , Substância Branca/diagnóstico por imagem , Pressão Sanguínea/genética , Imagem de Tensor de Difusão/métodos , Análise da Randomização Mendeliana , Bancos de Espécimes Biológicos , Envelhecimento/genética , Encéfalo/fisiologia , Reino UnidoRESUMO
In response to a study previously published in PLOS Biology, this Formal Comment thoroughly examines the concept of 'glucotypes' with regard to its generalisability, interpretability and relationship to more traditional measures used to describe data from continuous glucose monitoring.