Pearson Andrew G, Miller Kathleen B, Corkery Adam T, Eisenmann Nicole A, Howery Anna J, Cody Karly A, Chin Nathaniel A, Johnson Sterling C, Barnes Jill N
Bruno Balke Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, United States.
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, United States.
Front Aging Neurosci. 2022 Jul 11;14:888470. doi: 10.3389/fnagi.2022.888470. eCollection 2022.
Vascular dysfunction may occur prior to declines in cognitive function and accumulation of neuropathology. White matter hyperintensities (WMH) develop due to cerebral ischemia and elevated blood pressure in midlife. The purpose of this study was to evaluate associations between cardiovascular and cerebrovascular responses to sympathoexcitatory stimuli and WMH burden in cognitively unimpaired middle-aged and older adults. Sixty-eight adults (age = 63 ± 4y, men = 20, women = 48) participated in this study. Participants completed isometric handgrip exercise (IHG) exercise at 40% of maximal voluntary contraction until fatigue followed by a 90s period of post-exercise ischemia. Heart rate (HR), mean arterial pressure (MAP), middle cerebral artery blood velocity (MCAv), and end-tidal CO were continuously measured throughout the protocol. Cerebrovascular resistance index (CVRi) was calculated as MAP/MCAv. WMH lesion volume and intracranial volume (ICV) were measured using a FLAIR and T1 scan on a 3T MRI scanner, respectively. WMH fraction was calculated as (WMH lesion volume/ICV)*100 and cubic root transformed. Multiple linear regressions were used to determine the association between cardiovascular and cerebrovascular responses to IHG exercise and post-exercise ischemia and WMH fraction. Multiple linear regression models were adjusted for age, sex, apolipoprotein ε4 status, and total work performed during IHG exercise. During IHG exercise, there were significant increases from baseline in HR (25 ± 12%), MAP (27 ± 11%), MCAv (5 ± 10%), and CVRi (22 ± 17%; < 0.001 for all). During post-exercise ischemia, HR (8 ± 7%), MAP (22 ± 9%), and CVRi (23 ± 16%) remained elevated ( < 0.001) while MCAv (0 ± 10%) was not different compared to baseline. There was an inverse association between the percent change in HR (r = -0.42, = 0.002), MAP (r = -0.41, = 0.002), and CVRi (r = -0.31, = 0.045), but not MCAv (r = 0.19, = 0.971) in response to IHG exercise and WMH fraction. There were no associations between responses to post-exercise ischemia and WMH fraction. Lower sympathoexcitatory responses to IHG exercise are associated with greater WMH burden in middle-aged to older adults. These findings suggest that individuals who demonstrate smaller increases in HR, MAP, and CVRi in response to sympathoexcitatory stress have greater WMH burden.
血管功能障碍可能在认知功能下降和神经病理学积累之前就已出现。白质高信号（WMH）是由于中年时期的脑缺血和血压升高而形成的。本研究的目的是评估认知功能未受损的中年和老年人对交感神经兴奋刺激的心血管和脑血管反应与WMH负担之间的关联。68名成年人（年龄=63±4岁，男性=20名，女性=48名）参与了本研究。参与者以最大自主收缩力的40%进行等长握力运动（IHG），直至疲劳，随后是90秒的运动后缺血期。在整个实验过程中持续测量心率（HR）、平均动脉压（MAP）、大脑中动脉血流速度（MCAv）和呼气末二氧化碳（EtCO）。脑血管阻力指数（CVRi）计算为MAP/MCAv。使用3T MRI扫描仪上的液体衰减反转恢复序列（FLAIR）和T1加权扫描分别测量WMH病变体积和颅内体积（ICV）。WMH分数计算为（WMH病变体积/ICV）*100，并进行立方根转换。使用多元线性回归来确定对IHG运动和运动后缺血的心血管和脑血管反应与WMH分数之间的关联。多元线性回归模型对年龄、性别、载脂蛋白ε4状态以及IHG运动期间完成的总工作量进行了调整。在IHG运动期间，HR（25±12%）、MAP（27±11%）、MCAv（5±10%）和CVRi（22±17%；所有P<0.001）较基线均有显著增加。在运动后缺血期间，HR（8±7%）、MAP（22±9%）和CVRi（23±16%）仍保持升高（P<0.001），而MCAv（0±10%）与基线相比无差异。对IHG运动的HR（r=-0.42，P=0.002）、MAP（r=-0.41，P=0.002）和CVRi（r=-0.31，P=0.045）的百分比变化与WMH分数呈负相关，但MCAv（r=0.19，P=0.971）与WMH分数无关联。运动后缺血反应与WMH分数之间无关联。中年至老年成年人对IHG运动的交感神经兴奋反应较低与更大的WMH负担相关。这些发现表明，对交感神经兴奋应激时HR、MAP和CVRi升高幅度较小的个体具有更大的WMH负担。
