Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer's disease.
Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer's disease.
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DOI：
10.1007/s00401-016-1571-z
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发表时间：
2016-05
影响因子：
12.7
通讯作者：
Kalaria RN
中科院分区：
文献类型：
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作者：
Kalaria RN
血管性痴呆(VAD)被认为是一种神经认知障碍，在一般没有其他病理学的情况下，由多种血管原因解释。脑血管疾病的异质性给阐明VaD和血管认知障碍(VCI)的神经病理基础和机制带来了挑战。VaD的共识和准确诊断有赖于广泛的临床、神经心理和神经影像检查以及随后的病理证实。临床疑似VaD的病理诊断需要充分的死后脑标本和严格的评估方法来确定重要的底物。决定VaD亚型的因素包括血管病变的性质和程度、累及颅外和颅内血管的程度以及组织改变的解剖位置。动脉粥样硬化性和心源性栓塞性疾病是脑血管损伤或脑梗塞的最常见的底物。以动脉硬化和腔隙梗死为特征的小血管疾病也会导致皮质和皮质下微梗塞，这似乎是认知障碍的最强有力的底物。弥漫性WM改变伴髓鞘丢失和轴突异常在几乎所有的VaD亚型中都是常见的。同阿尔茨海默病一样，内侧颞叶和海马区萎缩并伴有可变的海马区硬化症也是VAD的特征。最近的观察表明，VaD患者颞叶和额叶的神经元萎缩是有血管基础的，这完全独立于任何阿尔茨海默病的病理。需要收集关于关键区域特定神经元和树突突触变化导致执行功能障碍和其他认知缺陷的进一步知识，这些缺陷定义了VCI和VAD。遗传性动脉病变，如伴有皮质下梗塞和白质脑病的常染色体显性遗传性脑动脉病或CADASIL，为了解与脑小血管疾病相关的痴呆的机制提供了洞察力。为了更好地确定痴呆的微血管疾病和血管底物，需要更多地了解神经化学和分子研究。相关动物模型的研究对于探讨认知障碍的发病机制和预防血管原因具有重要意义。
Vascular dementia (VaD) is recognised as a neurocognitive disorder, which is explained by numerous vascular causes in the general absence of other pathologies. The heterogeneity of cerebrovascular disease makes it challenging to elucidate the neuropathological substrates and mechanisms of VaD as well as vascular cognitive impairment (VCI). Consensus and accurate diagnosis of VaD relies on wide-ranging clinical, neuropsychometric and neuroimaging measures with subsequent pathological confirmation. Pathological diagnosis of suspected clinical VaD requires adequate postmortem brain sampling and rigorous assessment methods to identify important substrates. Factors that define the subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes. Atherosclerotic and cardioembolic diseases appear the most common substrates of vascular brain injury or infarction. Small vessel disease characterised by arteriolosclerosis and lacunar infarcts also causes cortical and subcortical microinfarcts, which appear to be the most robust substrates of cognitive impairment. Diffuse WM changes with loss of myelin and axonal abnormalities are common to almost all subtypes of VaD. Medial temporal lobe and hippocampal atrophy accompanied by variable hippocampal sclerosis are also features of VaD as they are of Alzheimer’s disease. Recent observations suggest that there is a vascular basis for neuronal atrophy in both the temporal and frontal lobes in VaD that is entirely independent of any Alzheimer pathology. Further knowledge on specific neuronal and dendro-synaptic changes in key regions resulting in executive dysfunction and other cognitive deficits, which define VCI and VaD, needs to be gathered. Hereditary arteriopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL have provided insights into the mechanisms of dementia associated with cerebral small vessel disease. Greater understanding of the neurochemical and molecular investigations is needed to better define microvascular disease and vascular substrates of dementia. The investigation of relevant animal models would be valuable in exploring the pathogenesis as well as prevention of the vascular causes of cognitive impairment.