Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study
Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study
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DOI：
10.1016/s1474-4422(19)30228-5
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发表时间：
2019-10-01
期刊：
影响因子：
48
通讯作者：
Schott, Jonathan M.
中科院分区：
文献类型：
--
作者：
Lane, Christopher A.;Barnes, Josephine;Schott, Jonathan M.
背景：中年高血压增加了晚年认知损害的风险。风险暴露的敏感期以及风险通过关节或血管相关机制传递的程度尚不清楚。我们的目标是确定血压或成年期血压变化是否以及何时与晚年大脑结构、病理和认知相关。方法参与者来自Insight 46，这是正在进行的纵向医学研究委员会全国健康与发展调查的神经科学子研究，出生队列最初包括1946年英国大陆一周内出生的5362人。年龄69-71岁的参与者在伦敦大学学院(英国伦敦)接受了T1和FLAIR容量磁共振成像、florbetapir淀粉样蛋白PET成像和认知评估；所有参与者都没有痴呆。血压测量是在36岁、43岁、53岁、60岁-和69岁收集的。我们还计算了不同年龄之间的血压变化变量。主要结果指标是使用自动化方法从多模式MRI定量的白质高强度体积(WMHV)，使用标准化摄取值比率方法定量的淀粉样蛋白(3)阳性或阴性，通过3D-T1 MRI定量的全脑和海马体体积，以及综合认知评分-临床前阿尔茨海默病认知复合体(PACC)。我们研究了36、43、53、60-和69岁之间的血压和血压变化与WMHV的关系，使用具有伽玛分布和对数链接函数的广义线性模型，使用Logistic回归方法研究了Arnyloid-0状态，使用线性回归方法研究了全脑体积和海马体体积，使用线性回归方法研究了PAcc评分，并对潜在的混杂因素进行了调整。465名参与者(238名151%的男性；平均年龄70.7岁[SD 0.7J；83118%的1名淀粉样β蛋白阳性]被纳入成像分析。53岁时较高的收缩压(SBP)和舒张压(DBP)以及43~53岁间SBP和DBP的较大幅度增加与69~71岁年龄段的WMHV呈正相关(平均每10 mm HgWMHV增加7%，95%可信区间1~14，p=0。024；平均WMHV每10 mm Hg增加15%，4-27，p=0。平均WMHV每改变一个SD SBP增加15%，3-29，p=0。舒张压每改变1个SD，平均WMHV增加15%，3-30，p=0.017)。43岁时较高的舒张压与69-71岁时较小的全脑体积相关(每10毫米汞柱较大的舒张压为-6.9毫升，-11.9至-1.9，p=0。0068)，36~43岁的DBP增幅较大(-6.5INL/1SD，-11.1~-1.9，NO-0054)。在36-43岁年龄段，收缩压升高较大与69-71岁年龄段较小的海马体体积相关(-0.03mL/1SD变化，-0.06--0.001，p=0.043)。绝对血压和血压变化都不能预测69-71岁的淀粉样β蛋白状态或PACC评分。从成年早期到中年，解释高和血压升高似乎与69-71岁的WMHV增加和脑体积变小有关。我们没有发现这个年龄段的血压影响认知或大脑淀粉样β蛋白负荷的证据。血压监测和干预可能需要在40岁左右开始，以最大限度地促进晚年大脑健康。版权所有(C)2019作者(S)。爱思唯尔有限公司出版。
Background Midlife hypertension confers increased risk for cognitive impairment in late life. The sensitive period for risk exposure and extent that risk is mediated through arnyloid or vascular-related mechanisms are poorly understood. We aimed to identify if, and when, blood pressure or change in blood pressure during adulthood were associated with late-life brain structure, pathology, and cognition.Methods Participants were from Insight 46, a neuroscience substudy of the ongoing longitudinal Medical Research Council National Survey of Health and Development, a birth cohort that initially comprised 5362 individuals born throughout mainland Britain in one week in 1946. Participants aged 69-71 years received T1 and FLAIR volumetric MRI, florbetapir amyloid-PET imaging, and cognitive assessment at University College London (London, UK); all participants were dementia-free. Blood pressure measurements had been collected at ages 36, 43, 53, 60-64, and 69 years. We also calculated blood pressure change variables between ages. Primary outcome measures were white matter hyperintensity volume (WMHV) quantified from multimodal MRI using an automated method, amyloid-(3 positivity or negativity using a standardised uptake value ratio approach, whole-brain and hippocarnpal volumes quantified from 3D-T1 MRI, and a composite cognitive score-the Preclinical Alzheimer Cognitive Composite (PACC). We investigated associations between blood pressure and blood pressure changes at and between 36, 43, 53, 60-64, and 69 years of age with WMHV using generalised linear models with a gamma distribution and log link function, arnyloid-0 status using logistic regression, whole-brain volume and hippocarnpal volumes using linear regression, and PACC score using linear regression, with adjustment for potential confounders.Findings Between May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. 465 participants (238 151%1 men; mean age 70.7 years [SD 0.7J; 83 118%1 amyloid-beta-positive) were included in imaging analyses. Higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) at age 53 years and greater increases in SBP and DBP between 43 and 53 years were positively associated with WMHV at 69-71 years of age (increase in mean WMHV per 10 mm Hg greater SBP 7%, 95% CI 1-14, p=0 . 024; increase in mean WMHV per 10 mm Hg greater DBP 15%, 4-27, p=0 . 0057; increase in mean WMHV per one SD change in SBP 15%, 3-29, p=0 . 012; increase in mean WMHV per 1 SD change in DBP 15%, 3-30, p=0.017). Higher DBP at 43 years of age was associated with smaller whole-brain volume at 69-71 years of age (-6.9 mL per 10 mm Hg greater DBP, -11.9 to -1.9, p=0 . 0068), as were greater increases in DBP between 36 and 43 years of age (-6.5 inL per 1 SD change, -11.1 to -1.9, NO-0054). Greater increases in SBP between 36 and 43 years of age were associated with smaller hippocampal volumes at 69-71 years of age (-0.03 mL per 1 SD change, -0.06 to -0.001, p=0.043). Neither absolute blood pressure nor change in blood pressure predicted amyloid-beta status or PACC score at 69-71 years of age.Interpretation High and increasing blood pressure from early adulthood into midlife seems to be associated with increased WMHV and smaller brain volumes at 69-71 years of age. We found no evidence that blood pressure affected cognition or cerebral amyloid-beta load at this age. Blood pressure monitoring and interventions might need to start around 40 years of age to maximise late-life brain health. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.