血管因素导致认知障碍和痴呆(VCID)生物标志物的未来:阿尔伯特白质与认知研究所2025年度研讨会会议记录

The future of biomarkers for vascular contributions to cognitive impairment and dementia (VCID): proceedings of the 2025 annual workshop of the Albert research institute for white matter and cognition.

作者信息

Lennon Matthew J, Karvelas Nikolaos, Ganesh Aravind, Whitehead Shawn, Sorond Farzaneh A, Durán Laforet Violeta, Head Elizabeth, Arfanakis Konstantinos, Kolachalama Vijaya B, Liu Xiao, Lu Hanzhang, Ramirez Joel, Walker Keenan, Weekman Erica, Wellington Cheryl L, Winston Charisse, Barone Frank C, Corriveau Roderick A

机构信息

Centre for Healthy Brain Aging (CHeBA), Discipline of Psychiatry & Mental Health, School of Clinical Medicine, University of New South Wales, Sydney NSW, Australia.

Northern Sydney Local Health District, NSW Health, Sydney NSW, Australia.

出版信息

Geroscience. 2025 Jun 21. doi: 10.1007/s11357-025-01746-y.

Abstract

Advances in biomarkers and pathophysiology of vascular contributions to cognitive impairment and dementia (VCID) are expected to bring greater mechanistic insights, more targeted treatments, and potentially disease-modifying therapies. The 2025 Annual Workshop of the Albert Research Institute for White Matter and Cognition, sponsored by the Leo and Anne Albert Charitable Trust since 2015, focused on novel biomarkers for VCID. The meeting highlighted the complexity of dementia, emphasizing that the majority of cases involve multiple brain pathologies, with vascular pathology typically present. Potential novel approaches to diagnosis of disease processes and progression that may result in VCID included measures of microglial senescence and retinal changes, as well as artificial intelligence (AI) integration of multimodal datasets. Proteomic studies identified plasma proteins associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; a rare genetic disorder affecting brain vessels) and age-related vascular pathology that suggested potential therapeutic targets. Blood-based microglial and brain-derived extracellular vesicles are promising tools for early detection of brain inflammation and other changes that have been associated with cognitive decline. Imaging measures of blood perfusion, oxygen extraction, and cerebrospinal fluid (CSF) flow were discussed as potential VCID biomarkers, in part because of correlations with classic pathological Alzheimer's disease (AD) biomarkers. MRI-visible perivascular spaces, which may be a novel imaging biomarker of sleep-driven glymphatic waste clearance dysfunction, are associated with vascular risk factors, lower cognitive function, and various brain pathologies including Alzheimer's, Parkinson's and cerebral amyloid angiopathy (CAA). People with Down syndrome are at high risk for dementia. Individuals with Down syndrome who develop dementia almost universally experience mixed brain pathologies, with AD pathology and cerebrovascular pathology being the most common. This follows the pattern in the general population where mixed pathologies are also predominant in the brains of people clinically diagnosed with dementia, including AD dementia. Intimate partner violence-related brain injury, hypertension's impact on dementia risk, and the promise of remote ischemic conditioning for treating VCID were additional themes.

摘要

血管性认知障碍和痴呆(VCID)的生物标志物及病理生理学进展有望带来更深入的机制见解、更具针对性的治疗方法以及潜在的疾病修饰疗法。自2015年以来由利奥和安妮·阿尔伯特慈善信托基金赞助的阿尔伯特白质与认知研究所2025年度研讨会聚焦于VCID的新型生物标志物。会议强调了痴呆的复杂性,指出大多数病例涉及多种脑部病变,血管病变通常存在。可能导致VCID的疾病过程和进展的潜在新诊断方法包括小胶质细胞衰老和视网膜变化的测量,以及多模态数据集的人工智能(AI)整合。蛋白质组学研究确定了与伴有皮质下梗死和白质脑病的脑常染色体显性动脉病(CADASIL,一种影响脑血管的罕见遗传病)以及与年龄相关的血管病变相关的血浆蛋白,这些病变提示了潜在的治疗靶点。基于血液的小胶质细胞和脑源性细胞外囊泡是早期检测与认知衰退相关的脑部炎症和其他变化的有前景的工具。血液灌注、氧提取和脑脊液(CSF)流动的成像测量被讨论为潜在的VCID生物标志物,部分原因是它们与经典的阿尔茨海默病(AD)病理生物标志物相关。MRI可见的血管周围间隙可能是睡眠驱动的类淋巴废物清除功能障碍的新型成像生物标志物,与血管危险因素、较低的认知功能以及包括阿尔茨海默病、帕金森病和脑淀粉样血管病(CAA)在内的各种脑部病变相关。唐氏综合征患者患痴呆的风险很高。患有痴呆的唐氏综合征个体几乎普遍经历混合性脑部病变,其中AD病理和脑血管病理最为常见。这与普通人群的模式一致,在临床诊断为痴呆的人群(包括AD痴呆)的大脑中,混合病变也占主导地位。亲密伴侣暴力相关的脑损伤、高血压对痴呆风险的影响以及远程缺血预处理治疗VCID的前景是其他主题。

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