Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alzheimers Dement. 2013 Jan;9(1):76-92. doi: 10.1016/j.jalz.2012.02.007. Epub 2012 Nov 22.
Vascular disease was once considered the principal cause of aging-related dementia. More recently, however, research emphasis has shifted to studies of progressive neurodegenerative disease processes, such as those giving rise to neuritic plaques, neurofibrillary tangles, and Lewy bodies. Although these studies have led to critical insights and potential therapeutic strategies, interest in the role of systemic and cerebrovascular disease mechanisms waned and has received relatively less attention and research support. Recent studies suggest that vascular disease mechanisms play an important role in the risk for aging-related cognitive decline and disorders. Vascular disease frequently coexists with cognitive decline in aging individuals, shares many risk factors with dementias considered to be of the "Alzheimer type," and is observed more frequently than expected in postmortem material from individuals manifesting "specific" disease stigmata, such as abundant plaques and tangles. Considerable difficulties have emerged in attempting to classify dementias as being related to vascular versus neurodegenerative causes, and several systems of criteria have been used. Despite multiple attempts, a lack of consensus remains regarding the optimal means of incorporating vascular disease into clinical diagnostic, neurocognitive, or neuropathologic classification schemes for dementias. We propose here an integrative, rather than a strictly taxonomic, approach to the study and elucidation of how vascular disease mechanisms contribute to the development of dementias. We argue that, instead of discriminating between, for example, "Alzheimer's disease," "vascular dementia," and other diseases, there is a greater need to focus clinical and research efforts on elucidating specific pathophysiologic mechanisms that contribute to dementia phenotypes and neuropathologic outcomes. We outline a multitiered strategy, beginning with clinical and public health interventions that can be implemented immediately, enhancements to ongoing longitudinal studies to increase their informative value, and new initiatives to capitalize on recent advances in systems biology and network medicine. This strategy will require funding from multiple public and private sources to support collaborative and interdisciplinary research efforts to take full advantage of these opportunities and realize their societal benefits.
血管疾病曾被认为是与衰老相关的痴呆的主要原因。然而，最近研究的重点已经转移到了对进行性神经退行性疾病过程的研究上，例如引起神经纤维缠结、神经原纤维缠结和路易体的疾病。虽然这些研究带来了重要的见解和潜在的治疗策略，但人们对系统性和脑血管疾病机制的兴趣减弱，得到的关注和研究支持相对较少。最近的研究表明，血管疾病机制在与衰老相关的认知能力下降和障碍的风险中起着重要作用。血管疾病在衰老个体中经常与认知能力下降共存，与被认为是“阿尔茨海默病型”的痴呆症有许多共同的危险因素，并且在表现出大量斑块和缠结等“特定”疾病特征的个体的尸检材料中观察到的频率高于预期。在试图将痴呆症分类为与血管或神经退行性原因相关时，出现了相当大的困难，并且已经使用了几种分类标准。尽管进行了多次尝试，但在将血管疾病纳入痴呆症的临床诊断、神经认知或神经病理分类方案方面，仍然缺乏共识。我们在这里提出了一种综合的方法，而不是严格的分类方法，来研究和阐明血管疾病机制如何导致痴呆症的发展。我们认为，与其区分例如“阿尔茨海默病”、“血管性痴呆”和其他疾病，不如更加需要关注阐明有助于痴呆症表型和神经病理学结果的具体病理生理机制的临床和研究工作。我们概述了一个多层次的策略，从可以立即实施的临床和公共卫生干预措施开始，增强正在进行的纵向研究以提高其信息价值，以及利用系统生物学和网络医学的最新进展的新举措。这项策略将需要来自多个公共和私人来源的资金，以支持协作和跨学科的研究工作，充分利用这些机会并实现其社会效益。
