It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aβ) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes) with cognition. Using mediation analyses, we tested the indirect effects of WMH on cognition via Aβ deposition (¹⁸F-AV45 positron emission tomography [PET]) and neurodegeneration (cortical thickness or ¹⁸F fluorodeoxyglucose PET) in AD signature regions. We observed that increased total WMH volume was associated with poorer performance in all tested cognitive domains, with the strongest effects observed for semantic fluency. These relationships were mediated mainly via cortical thinning, particularly of the temporal lobe, and to a lesser extent serially mediated via Aβ and cortical thinning of AD signature regions. WMH volumes differentially impacted cognition depending on lobar location and Aβ status. In summary, our study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive function via localized neurodegeneration.

中文翻译：

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血管负担和认知：神经变性和淀粉样蛋白 PET 的中介作用

目前尚不清楚在患有小血管病和阿尔茨海默病 (AD) 病理的混合疾病人群中，脑血管负担在多大程度上与淀粉样蛋白 (Aβ) 沉积、神经变性和认知功能障碍相关。在 120 名受试者中，我们调查了血管负荷（白质高信号 [WMH] 体积）与认知之间的关联。使用中介分析，我们测试了 WMH 通过 Aβ 沉积（¹⁸ F-AV45 正电子发射断层扫描 [PET]）和神经变性（皮质厚度或¹⁸F 氟脱氧葡萄糖 PET) 在 AD 特征区域。我们观察到，增加的 WMH 总量与所有测试认知领域的较差表现相关，其中对语义流畅性的影响最强。这些关系主要是通过皮质变薄介导的，特别是颞叶的皮质变薄，并且在较小程度上通过 Aβ 和 AD 特征区域的皮质变薄连续介导。WMH 体积对认知的影响因脑叶位置和 Aβ 状态而异。总之，我们的研究表明主要是一种淀粉样蛋白非依赖性途径，其中血管负担通过局部神经变性影响认知功能。