性别对心脏代谢健康和大脑年龄的影响：一项纵向队列研究。
Sex-Dependent Effects of Cardiometabolic Health and on Brain Age: A Longitudinal Cohort Study.
机构信息
From the Department of Clinical Neuroscience (S.S., L.S.S., A.-M.G.d.L.), Lausanne University Hospital and University of Lausanne, Switzerland; Department of Psychology (P.R., M.E.B., J.M.W., M.V.H., S.M.M., B.A., J.C., T.C.R., S.R.C.), University of Edinburgh, United Kingdom; Department of Psychology (L.T.W.), University of Oslo, Norway; Dementia Research Centre (W.C., J.G., D.M.C., J.B., S.-N.J., C.H.S., J.M.S.), Centre for Medical Image Computing (C.H.S., F.B., J.H.C.), and MRC Unit for Lifelong Health and Ageing (M.R., S.-N.J., C.H.S.), University College London, United Kingdom.
出版信息
Neurology. 2024 Sep 24;103(6):e209744. doi: 10.1212/WNL.0000000000209744. Epub 2024 Aug 22.
BACKGROUND AND OBJECTIVES
The aging population is growing faster than all other demographic strata. With older age comes a greater risk of health conditions such as obesity and high blood pressure (BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging, yet their influence on brain health in females vs males is largely unexplored. In this study, we investigated sex differences in relationships between BP, body mass index (BMI), and brain age over time and tested for interactions with ε4 genotype (), a known genetic risk factor of Alzheimer disease.
METHODS
The sample included participants from 2 United Kingdom-based longitudinal birth cohorts, the Lothian Birth Cohort (1936) and Insight 46 (1946). Participants with MRI data from at least 1 time point were included to evaluate sex differences in associations between CMRs and brain age. The open-access software package brainageR 2.1 was used to estimate brain age for each participant. Linear mixed-effects models were used to assess the relationships between brain age, BMI, BP, and status (i.e., carrier vs noncarrier) in males and females over time.
RESULTS
The combined sample comprised 1,120 participants (48% female) with a mean age (SD) of 73 (0.72) years in the Lothian Birth Cohort and 71 (0.68) years in Insight 46 at the time point 1 assessment. Approximately 30% of participants were carriers. Higher systolic and diastolic BP was significantly associated with older brain age in females only (β = 0.43-0.56, < 0.05). Among males, higher BMI was associated with older brain age across time points and groups (β = 0.72-0.77, < 0.05). In females, higher BMI was linked to older brain age among noncarriers (β = 0.68-0.99, < 0.05), whereas higher BMI was linked to younger brain age among carriers, particularly at the last time point (β = -1.75, < 0.05).
DISCUSSION
This study indicates sex-dependent and time-dependent relationships between CMRs, status, and brain age. Our findings highlight the necessity of sex-stratified analyses to elucidate the role of CMRs in individual aging trajectories, providing a basis for developing personalized preventive interventions.
背景和目的
人口老龄化速度快于其他所有人口阶层。随着年龄的增长，肥胖和高血压（BP）等健康状况的风险也会增加。这些心血管代谢危险因素（CMRs）在中年和老年时表现出明显的性别差异，但它们对女性和男性大脑健康的影响在很大程度上尚未得到探索。在这项研究中，我们研究了 BP、体重指数（BMI）和大脑年龄随时间的关系中的性别差异，并测试了与 ε4 基因型（）的相互作用，该基因型是阿尔茨海默病的已知遗传危险因素。
方法
该样本包括来自 2 个英国基于纵向出生队列的参与者，即洛锡安出生队列（1936 年）和洞察 46 队列（1946 年）。至少有 1 个时间点的 MRI 数据的参与者被纳入研究，以评估 CMRs 和大脑年龄之间关联的性别差异。使用开放获取软件包 brainageR 2.1 来估计每个参与者的大脑年龄。线性混合效应模型用于评估男性和女性大脑年龄、BMI、BP 和 状态（即携带者与非携带者）随时间的关系。
结果
合并样本包括 1120 名参与者（48%为女性），洛锡安出生队列的平均年龄（SD）为 73（0.72）岁，洞察 46 队列的平均年龄（SD）为 71（0.68）岁，在第一次评估时。大约 30%的参与者是 携带者。在女性中，较高的收缩压和舒张压与大脑年龄较大显著相关（β=0.43-0.56，<0.05）。在男性中，较高的 BMI 与各个时间点和 组的大脑年龄较大相关（β=0.72-0.77，<0.05）。在女性中，较高的 BMI 与非携带者的大脑年龄较大相关（β=0.68-0.99，<0.05），而在携带者中，较高的 BMI 与大脑年龄较小相关，尤其是在最后一个时间点（β=-1.75，<0.05）。
讨论
本研究表明 CMRs、 状态和大脑年龄之间存在性别依赖和时间依赖的关系。我们的研究结果强调了进行性别分层分析以阐明 CMRs 在个体衰老轨迹中的作用的必要性，为制定个性化的预防干预措施提供了依据。
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