Importance Aortic stiffness is associated with clinical hallmarks of Alzheimer disease and related dementias and could be a modifiable target for disease prevention. Objective To assess associations of aortic stiffness and pressure pulsatility with global amyloid-β plaques and regional tau burden in the brain of middle-aged and older adults without dementia. Design, Setting, and Participants The sample for this cross-sectional study was drawn from the Framingham Heart Study Third Generation Cohort at examination 3 (N = 3171; 2016-2019), of whom 3092 successfully underwent comprehensive hemodynamic evaluations. In a supplemental visit (2015-2021), a subset of 270 participants without dementia who represented the spectrum of vascular risk also underwent positron emission tomography. Thirteen participants were excluded for missing covariate data. The final sample size was 257 participants. Exposures Three measures of aortic stiffness and pressure pulsatility (carotid-femoral pulse wave velocity, central pulse pressure [CPP], and forward wave amplitude [FWA]) were evaluated using arterial tonometry. Main Outcomes and Measures Global amyloid-β plaques and regional tau were assessed using 11C-Pittsburgh compound B and 18F-flortaucipir positron emission tomography tracers, respectively. Results The mean (SD) age of the 257 participants was 54 (8) years, and 126 were women (49%). All participants were White Western European race. In multivariable models, higher CPP (β per SD = 0.17; 95% CI, 0.00-0.35; P = .045) and FWA (β per SD = 0.16; 95% CI, 0.00-0.31; P = .04) were associated with greater entorhinal tau burden. In similar models, higher CPP (β per SD = 0.19; 95% CI, 0.02-0.36; P = .03) and FWA (β per SD = 0.17; 95% CI, 0.01-0.32; P = .03) were associated with greater rhinal tau burden. Aortic stiffness and pressure pulsatility measures were not associated with amygdala, inferior temporal, precuneus tau burden, or global amyloid-β plaques. Associations for entorhinal and rhinal tau outcomes were more prominent in older participants (≥60 years). For example, higher levels of all aortic stiffness and pressure pulsatility measures (β per SD = 0.40-0.92; P = .001-.02) were associated with higher entorhinal tau burden among older but not younger participants in stratified analyses. Conclusions and Relevance In this cross-sectional study, abnormal central vascular hemodynamics were associated with higher tau burden in specific brain regions. Findings suggest that aortic stiffness, which is potentially modifiable, may be a probable independent target for prevention of tau-related pathologies.

中文翻译：

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在没有痴呆症的 Framingham 心脏研究参与者中，主动脉僵硬度和压力脉动与全球淀粉样蛋白-β 和区域 Tau 负荷的关联。

重要性 主动脉僵硬与阿尔茨海默病和相关痴呆症的临床特征相关，可能成为疾病预防的可修改目标。目的 评估主动脉僵硬度和压力搏动与无痴呆症中老年人大脑中全脑淀粉样蛋白-β斑块和区域 tau 负荷的相关性。设计、设置和参与者 本横断面研究的样本来自弗雷明汉心脏研究第三代队列检查 3（N = 3171；2016-2019），其中 3092 人成功进行了全面的血液动力学评估。在补充访问（2015-2021 年）中，代表血管风险范围的 270 名没有痴呆症的参与者也接受了正电子发射断层扫描。13 名参与者因缺少协变量数据而被排除在外。最终样本量为 257 名参与者。暴露 主动脉硬度和压力脉动的三种测量方法（颈动脉-股动脉脉搏波速度、中心脉压 [CPP] 和前向波振幅 [FWA]）使用动脉眼压测量法进行评估。主要成果和措施 分别使用 11C-Pittsburgh 化合物 B 和 18F-flortaucipir 正电子发射断层扫描示踪剂评估全球淀粉样蛋白-β 斑块和区域 tau 蛋白。结果 257 名参与者的平均 (SD) 年龄为 54 (8) 岁，其中 126 名是女性 (49%)。所有参与者都是西欧白人。在多变量模型中，较高的 CPP（β/SD = 0.17；95% CI，0.00-0.35；P = .045）和 FWA（β/SD = 0.16；95% CI，0.00-0.31；P = .04）相关具有更大的内嗅 tau 负荷。在类似模型中，更高的 CPP（β/SD = 0.19；95% CI，0.02-0.36；P = . 03) 和 FWA（β/SD = 0.17；95% CI，0.01-0.32；P = .03）与更大的鼻腔 tau 负荷相关。主动脉僵硬度和压力脉动测量与杏仁核、下颞叶、楔前叶 tau 负荷或全球淀粉样蛋白-β 斑块无关。内嗅和鼻腔 tau 结果的相关性在老年参与者（≥60 岁）中更为突出。例如，在分层分析中，较高水平的所有主动脉硬度和压力脉动测量值（β/SD = 0.40-0.92；P = .001-.02）与较高的内嗅 tau 负荷相关，但与较年轻的参与者无关。结论和相关性 在这项横断面研究中，中央血管血流动力学异常与特定脑区较高的 tau 负荷有关。研究结果表明，主动脉僵硬可能是可以改变的，