Zahra Shirzadi, Rory Boyle, Wai-Ying W Yau, Gillian Coughlan, Jessie Fanglu Fu, Michael J Properzi, Rachel F Buckley, Hyun-Sik Yang, Catherine E Scanlon, Stephanie Hsieh, Rebecca E Amariglio, Kathryn Papp, Dorene Rentz, Julie C Price, Keith A Johnson, Reisa A Sperling, Jasmeer P Chhatwal, Aaron P Schultz
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We used the following measures from the baseline visit: cortical amyloid, inferior temporal cortex tau, relative cerebral blood flow, white matter hyperintensities, peak width of skeletonized mean diffusivity, and Framingham Heart Study cardiovascular disease risk. We used exploratory factor analysis to extract orthogonal factors from these variables and their interactions. These factors were used in a regression model to explain longitudinal Preclinical Alzheimer Cognitive Composite-5 (PACC) decline (follow-up = 8.5 ±2.7 years). We next examined whether gray matter volume atrophy acts as a mediator of factors and PACC decline. Latent factors of systemic vascular risk, white matter injury, and relative cerebral blood flow independently explain cognitive decline beyond amyloid and tau. Gray matter volume atrophy mediates these associations with the strongest effect on white matter injury. 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引用次数: 0
摘要
除了淀粉样蛋白和 tau 病理学之外,全身血管风险升高、白质损伤和脑血流量减少也是导致晚年认知能力下降的原因。鉴于这些参数之间存在很强的共线性,我们提出了一个框架,利用哈佛大学老年脑研究(N = 166 名基线认知功能未受损的老年人)来提取认知功能衰退的独立潜在特征。我们使用了基线访问中的以下测量指标:皮层淀粉样蛋白、下颞皮层 tau、相对脑血流量、白质高密度、骨架化平均扩散峰值宽度和弗雷明汉心脏研究心血管疾病风险。我们使用探索性因子分析从这些变量及其交互作用中提取正交因子。这些因素被用于回归模型,以解释临床前阿尔茨海默氏症认知综合征-5(PACC)的纵向衰退(随访时间 = 8.5 ± 2.7 年)。接下来,我们研究了灰质体积萎缩是否是各种因素与 PACC 下降之间的中介。除淀粉样蛋白和tau外,全身血管风险、白质损伤和相对脑血流量等潜在因素也能独立解释认知能力的下降。灰质体积萎缩介导了这些关联,对白质损伤的影响最大。这些结果表明,除了目前的脑血管损伤、淀粉样蛋白和 tau 标记之外,系统性血管风险也是认知能力下降的原因之一。
Vascular contributions to cognitive decline: Beyond amyloid and tau in the Harvard Aging Brain Study.
In addition to amyloid and tau pathology, elevated systemic vascular risk, white matter injury, and reduced cerebral blood flow contribute to late-life cognitive decline. Given the strong collinearity among these parameters, we proposed a framework to extract the independent latent features underlying cognitive decline using the Harvard Aging Brain Study (N = 166 cognitively unimpaired older adults at baseline). We used the following measures from the baseline visit: cortical amyloid, inferior temporal cortex tau, relative cerebral blood flow, white matter hyperintensities, peak width of skeletonized mean diffusivity, and Framingham Heart Study cardiovascular disease risk. We used exploratory factor analysis to extract orthogonal factors from these variables and their interactions. These factors were used in a regression model to explain longitudinal Preclinical Alzheimer Cognitive Composite-5 (PACC) decline (follow-up = 8.5 ±2.7 years). We next examined whether gray matter volume atrophy acts as a mediator of factors and PACC decline. Latent factors of systemic vascular risk, white matter injury, and relative cerebral blood flow independently explain cognitive decline beyond amyloid and tau. Gray matter volume atrophy mediates these associations with the strongest effect on white matter injury. These results suggest that systemic vascular risk contributes to cognitive decline beyond current markers of cerebrovascular injury, amyloid, and tau.
期刊介绍:
JCBFM is the official journal of the International Society for Cerebral Blood Flow & Metabolism, which is committed to publishing high quality, independently peer-reviewed research and review material. JCBFM stands at the interface between basic and clinical neurovascular research, and features timely and relevant research highlighting experimental, theoretical, and clinical aspects of brain circulation, metabolism and imaging. The journal is relevant to any physician or scientist with an interest in brain function, cerebrovascular disease, cerebral vascular regulation and brain metabolism, including neurologists, neurochemists, physiologists, pharmacologists, anesthesiologists, neuroradiologists, neurosurgeons, neuropathologists and neuroscientists.