发现脑微出血与阿尔茨海默病认知衰退及病理积累密切相关。
Cerebral microbleeds: Association with cognitive decline and pathology build-up
- 分析1573名参与者脑微出血位置与认知、病理的关系。
- 颞叶微出血者语言、语义和执行功能下降更明显，伴全身皮层τ蛋白增加。
- 皮层微出血者β-淀粉样蛋白升高，提示其在诊断中具重要价值。
脑微出血是血管与淀粉样病变的标志，与衰老相关认知衰退有关，但在阿尔茨海默病（AD）发病和进展中的作用仍不明确。本研究分析了1573名来自ADNI队列的受试者，其具有磁共振成像数据及微出血数量和位置信息，探讨叶性微出血与β-淀粉样蛋白（Aβ-PET）、tau缠结（tau-PET）以及纵向认知衰退的关联。采用普通最小二乘回归分析区域微出血与认知域特异性衰退（使用ADAS-Cog11及其子量表）的关系，调整协变量。参与者至少接受两次神经心理学评估，间隔不少于两年。在1573名受试者（692名女性，平均年龄71.23岁）中，373人存在微出血。颞叶微出血者在语义、语言和运动功能领域衰退更显著；全皮层微出血与语言能力下降相关。病理上，颞叶微出血与全皮层tau蛋白升高有关，而皮层微出血则与颞、顶、额叶Aβ水平上升相关。在混合人群中，微出血与长期认知衰退，尤其是语义和语言领域相关，并与基线Aβ和tau病理负荷更高有关。结果表明，叶性微出血应纳入阿尔茨海默病的诊断与预后评估。
原文摘要 · Abstract (English)
Cerebral microbleeds, markers of brain damage from vascular and amyloid pathologies, are linked to cognitive decline in aging, but their role in Alzheimer's disease (AD) onset and progression remains unclear. This study aimed to explore whether the presence and location of lobar microbleeds are associated with amyloid-$β$ (A$β$)-PET, tau tangle formation (tau-PET), and longitudinal cognitive decline. We analyzed 1,573 ADNI participants with MR imaging data and information on the number and location of microbleeds. Associations between lobar microbleeds and pathology, cerebrospinal fluid (CSF), genetics, and cognition were examined, focusing on regional microbleeds and domain-specific cognitive decline using ordinary least-squares regression while adjusting for covariates. Cognitive decline was assessed with ADAS-Cog11 and its domain-specific sub-scores. Participants underwent neuropsychological testing at least twice, with a minimum two-year interval between assessments. Among the 1,573 participants (692 women, mean age 71.23 years), 373 participants had microbleeds. The presence of microbleeds was linked to cognitive decline, particularly in the semantic, language, and praxis domains for those with temporal lobe microbleeds. Microbleeds in the overall cortex were associated with language decline. Pathologically, temporal lobe microbleeds were associated with increased tau in the overall cortex, while cortical microbleeds were linked to elevated A$β$ in the temporal, parietal, and frontal regions. In this mixed population, microbleeds were connected to longitudinal cognitive decline, especially in semantic and language domains, and were associated with higher baseline A$β$ and tau pathology. These findings suggest that lobar microbleeds should be included in AD diagnostic and prognostic evaluations.
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