Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome.
Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome.
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DOI：
10.1186/alzrt155
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Black SE
中科院分区：
文献类型：
--
作者：
Lam B;Masellis M;Freedman M;Stuss DT;Black SE
随着对阿尔茨海默病（AD）的临床体内生物标志物和病理复杂性的认识不断增加，疾病分类学正在发展。强调原型疾病的统一共识标准继续发展，以实现治疗决策和临床试验的诊断清晰度。然而，很明显，AD在临床表现和进展方面具有异质性，表现出萎缩和代谢减退/灌注不足的不同地形分布。此外，AD经常与可能进一步细微差别临床表达的其他病症相伴，例如加剧执行和视觉空间功能障碍的突触核蛋白病和加重额叶执行障碍的血管病理（特别是随着人类衰老而越来越普遍的小血管疾病）。这些非典型临床模式中的一些复发可能意味着存在不同的AD变体。例如，局灶性颞叶功能障碍与纯粹的遗忘综合征相关，非常缓慢的衰退，萎缩和神经元缠结主要限于内侧颞区，包括内嗅皮质。左顶叶萎缩和/或代谢减退/灌注不足与语言症状、发病年龄较小和下降速度较快相关-AD的潜在“语言变体”。相反，同样的模式，但主要影响右顶叶与一个类似的综合征，但视觉空间症状取代受损的语言功能。最后，极其罕见的额叶变异与执行功能障碍有关，与记忆衰退的程度不一致，可能有突出的行为症状。基因型差异可能是这些亚型的基础;例如，载脂蛋白E e4的缺乏通常与年轻发病AD的遗传性相关。了解这种变异性背后的机制值得进一步研究，通过成像技术，生物标志物测定和定量病理学方法的最新进展，结合标准化的临床，功能，神经心理学和神经行为评估。需要这样的理解来促进“个性化AD药物”，并最终允许针对特定AD亚型的临床试验。虽然重点仍然是合理的原型疾病，继续努力开发疾病修饰疗法不应排除罕见的AD亚型和常见的共病表现，因为目前经常出现这种情况。只有对他们进行同样的治疗，我们才能解决这种毁灭性痴呆综合征的全部负担。
With increasing knowledge of clinical in vivo biomarkers and the pathological intricacies of Alzheimer's disease (AD), nosology is evolving. Harmonized consensus criteria that emphasize prototypic illness continue to develop to achieve diagnostic clarity for treatment decisions and clinical trials. However, it is clear that AD is clinically heterogeneous in presentation and progression, demonstrating variable topographic distributions of atrophy and hypometabolism/hypoperfusion. AD furthermore often keeps company with other conditions that may further nuance clinical expression, such as synucleinopathy exacerbating executive and visuospatial dysfunction and vascular pathologies (particularly small vessel disease that is increasingly ubiquitous with human aging) accentuating frontal-dysexecutive symptomatology. That some of these atypical clinical patterns recur may imply the existence of distinct AD variants. For example, focal temporal lobe dysfunction is associated with a pure amnestic syndrome, very slow decline, with atrophy and neurofibrillary tangles limited largely to the medial temporal region including the entorhinal cortex. Left parietal atrophy and/or hypometabolism/hypoperfusion are associated with language symptoms, younger age of onset, and faster rate of decline - a potential 'language variant' of AD. Conversely, the same pattern but predominantly affecting the right parietal lobe is associated with a similar syndrome but with visuospatial symptoms replacing impaired language function. Finally, the extremely rare frontal variant is associated with executive dysfunction out of keeping with degree of memory decline and may have prominent behavioural symptoms. Genotypic differences may underlie some of these subtypes; for example, absence of apolipoprotein E e4 is often associated with atypicality in younger onset AD. Understanding the mechanisms behind this variability merits further investigation, informed by recent advances in imaging techniques, biomarker assays, and quantitative pathological methods, in conjunction with standardized clinical, functional, neuropsychological and neurobehavioral evaluations. Such an understanding is needed to facilitate 'personalized AD medicine', and eventually allow for clinical trials targeting specific AD subtypes. Although the focus legitimately remains on prototypic illness, continuing efforts to develop disease-modifying therapies should not exclude the rarer AD subtypes and common comorbid presentations, as is currently often the case. Only by treating them as well can we address the full burden of this devastating dementia syndrome.
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影响因子：
8.3
作者：
Bombois, Stephanie;Debette, Stephanie;Pasquier, Florence
通讯作者：
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168.9
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11
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9.9
作者：
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