Ma Yuan, Bos Daniel, Wolters Frank J, Niessen Wiro, Hofman Albert, Ikram M Arfan, Vernooij Meike W
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (Y.M., A.H.).
Department of Epidemiology (D.B., F.J.W., A.H., M.A.I., M.W.V.), Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Stroke. 2025 Jan;56(1):95-104. doi: 10.1161/STROKEAHA.124.047593. Epub 2024 Dec 5.
Cerebral hypoperfusion is associated with vascular brain injury and neurodegeneration, but their longitudinal relationship is largely unknown, especially in healthy older adults.
We investigated the longitudinal relationship between cerebral hemodynamics and subclinical vascular brain disease in community-dwelling older adults without stroke or dementia at baseline. Participants underwent brain magnetic resonance imaging scans every 3 to 4 years between 2005 and 2016. Cerebral blood flow (CBF) was measured through 2-dimensional phase-contrast magnetic resonance imaging; the cerebrovascular resistance index (CVRi) was defined as the ratio of mean arterial blood pressure to total CBF. Simultaneous progression in subclinical brain disease was evaluated through repeated magnetic resonance imaging assessment of white matter hyperintensities (WMH), cerebral microbleeds, lacune, and brain atrophy. The longitudinal relationship was estimated using generalized estimating equations, with adjustment for age, sex, smoking habits, body mass index, systolic blood pressure (for CBF measures), lipid level, history of diabetes and cardiovascular disease, and the baseline burden of magnetic resonance imaging markers.
Among 3623 older adults (mean age, 61.4±9.3 years; 54.6% women), large decreases and increases in CBF and increases in CVRi over time were associated with white matter hyperintensity progression. The risk ratios for white matter hyperintensity progression were 1.36 (95% CI, 1.19-1.55) for large decreases in total CBF (lowest quartile), 1.02 (95% CI, 0.91-1.14) for moderate decreases (second quartile), and 1.28 (95% CI, 1.14-1.45) for large increases (highest quartile), compared with stable CBF (third quartile). The corresponding risk ratios for changes in CVRi were 1.13 (95% CI, 1.00-1.30), 1.25 (95% CI, 1.09-1.43), and 1.33 (95% CI, 1.16-1.52) for the second to fourth (versus lowest) quartiles, respectively, showing a dose-response relationship. The changes in CBF also demonstrate a similar U-shaped association with the progression of brain atrophy and incident microbleeds, whereas increases in CVRi were associated with lower microbleed risk.
Longitudinal changes in CBF and CVRi may capture distinct pathophysiologies linking cerebral hemodynamics to subclinical brain disease, extending beyond single-time point measurements.
脑灌注不足与脑血管损伤和神经退行性变相关，但其纵向关系在很大程度上尚不清楚，尤其是在健康的老年人中。
我们研究了社区居住的无卒中或痴呆的老年人中脑血流动力学与亚临床脑血管疾病之间的纵向关系。参与者在2005年至2016年期间每3至4年接受一次脑磁共振成像扫描。通过二维相位对比磁共振成像测量脑血流量（CBF）；脑血管阻力指数（CVRi）定义为平均动脉血压与总CBF的比值。通过对白质高信号（WMH）、脑微出血、腔隙和脑萎缩的重复磁共振成像评估来评估亚临床脑疾病的同时进展。使用广义估计方程估计纵向关系，并对年龄、性别、吸烟习惯、体重指数、收缩压（用于CBF测量）、血脂水平、糖尿病和心血管疾病史以及磁共振成像标记物的基线负担进行调整。
在3623名老年人（平均年龄61.4±9.3岁；54.6%为女性）中，随着时间的推移，CBF的大幅下降和增加以及CVRi的增加与白质高信号进展相关。总CBF大幅下降（最低四分位数）时白质高信号进展的风险比为1.36（95%CI，1.19-1.55），中度下降（第二四分位数）时为1.02（95%CI，0.91-1.14），大幅增加（最高四分位数）时为1.28（95%CI，1.14-1.45），与稳定的CBF（第三四分位数）相比。CVRi变化的相应风险比分别为第二至第四（与最低）四分位数的1.13（95%CI，1.00-1.30）、1.25（95%CI，1.09-1.43）和1.33（95%CI，1.16-1.52），呈现剂量反应关系。CBF的变化也显示出与脑萎缩进展和新发微出血的类似U形关联，而CVRi的增加与较低的微出血风险相关。
CBF和CVRi的纵向变化可能反映了将脑血流动力学与亚临床脑疾病联系起来的不同病理生理学，这超出了单点测量的范围。
