Supplementary results for: Visit-to-visit blood pressure variability, neuropathology and cognitive function

Objective Large systolic blood pressure (SBP) variability has been proposed as a novel risk factor for dementia above and beyond SBP levels, but the underlying neuropathology is largely unknown. We investigated the relationship among visit-to-visit SBP variability, cognitive deterioration and underlying neuropathological changes.

Methods We used longitudinal data (between 2005 and 2019) from the National Alzheimer’s Coordinating Center. 13,284 dementia-free participants aged≥50 years were followed over a median of 5.0 (interquartile range: 3.1-7.6) years. Neuropathology data were available in 1,400 autopsied participants. Visit-to-visit SBP variability was quantified from repeated annual SBP measurements. Cognitive deterioration was defined as conversion from normal cognition to mild cognitive impairment (MCI) or dementia, or from MCI to dementia.

Results Larger visit-to-visit SBP variability was associated with cognitive deterioration (adjusted odds ratio comparing extreme quintiles: 2.64; 95%CI:2.29-3.04, P <0.001). It was also associated with a higher burden of vascular pathology (including microinfarcts, white matter lesion, atherosclerosis of the circle of Willis and arteriolosclerosis) and with neurofibrillary tangle pathology assessed by Braak staging (All P < 0.05). The association with cognitive deterioration and vascular pathology appeared stronger among those with normal cognition versus MCI at baseline. These findings were observed after adjusting for age, sex, mean SBP and other confounding variables. Similar results were observed for diastolic BP variability.

Conclusion Larger visit-to-visit SBP variability was associated with cognitive deterioration. It was also associated with cerebrovascular pathology and neurofibrillary tangles. These results suggest the intertwined role of vascular and Alzheimer's disease pathology in the etiology of dementia.

【研究背景】已有研究提出，相较于单纯的收缩压（systolic blood pressure, SBP）水平，访视间收缩压变异性可作为痴呆的新型危险因素，但潜在的神经病理学机制仍尚未明确。本研究旨在探讨访视间收缩压变异性、认知衰退与潜在神经病理改变之间的关联。
【研究方法】本研究使用了国家阿尔茨海默病协调中心（National Alzheimer’s Coordinating Center）2005年至2019年的纵向随访数据。共纳入13284名基线无痴呆、年龄≥50岁的参与者，中位随访时间为5.0年（四分位间距：3.1~7.6年）。其中1400名接受尸检的参与者具备完整的神经病理学数据。通过年度重复收缩压测量值量化访视间收缩压变异性。认知衰退定义为：从正常认知进展为轻度认知障碍（mild cognitive impairment, MCI）或痴呆，或从轻度认知障碍进展为痴呆。
【研究结果】更高的访视间收缩压变异性与认知衰退显著相关（对比最高与最低五分位组的校正优势比为2.64；95%置信区间：2.29~3.04，P<0.001）。同时，该变异性还与更高的血管病理负荷（包括微梗死、白质病变、威利斯环动脉粥样硬化及小动脉硬化）以及经Braak分期评估的神经原纤维缠结病理显著相关（所有P<0.05）。在基线为正常认知的参与者中，访视间收缩压变异性与认知衰退及血管病理的关联强度，相较于基线为轻度认知障碍的参与者更为显著。上述关联在校正年龄、性别、平均收缩压及其他混杂变量后仍具有统计学意义。舒张压变异性也得到了相似的研究结果。
【研究结论】更高的访视间收缩压变异性与认知衰退显著相关，同时也与脑血管病理及神经原纤维缠结存在关联。本研究结果提示，血管病理与阿尔茨海默病（Alzheimer's disease）病理在痴呆的发病机制中存在相互交织的作用。