von Gunten Armin, Bouras Constantin, Kövari Enikö, Giannakopoulos Panteleimon, Hof Patrick R
Division of Old Age Psychiatry, Department of Psychiatry-CHUV, Prilly-Lausanne, Switzerland.
Brain Res Rev. 2006 Aug;51(2):176-211. doi: 10.1016/j.brainresrev.2005.11.003. Epub 2006 Jan 18.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive cognitive decline that typically affects first memory and later executive functions, language, and visuospatial skills. This sequence of cognitive deterioration is thought to reflect the progressive invasion of the cerebral cortex by the two major pathological hallmarks of AD, neurofibrillary tangles (NFT) and senile plaques (SP), as well as degree of neuronal and synaptic loss. In atypical AD, prominent and early deficits are found in language, motor abilities, frontal and executive capacities, or visuospatial skills. These atypical clinical features are associated with an unusual pattern of NFT or SP formation that predominantly involves cortical areas usually spared in the course of the degenerative process. In an attempt to classify this highly heterogeneous subgroup, the present article provides an overview of clinicopathological analyses in patients with atypical progression of AD symptomatology with special reference to the relationship between specific cognitive and behavioral deficits and hierarchical patterns of AD lesion distribution within the cerebral cortex. On the basis of these representative examples of a cortical circuit-based approach to explore the mechanisms giving rise to AD neuropsychological expression, we also critically discuss the possibility to develop a matrix linking clinical presentations to degeneration of forward and backward long corticocortical pathways in this disorder.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是进行性认知衰退，通常首先影响记忆，随后影响执行功能、语言和视觉空间技能。这种认知恶化的顺序被认为反映了AD的两个主要病理特征——神经原纤维缠结（NFT）和老年斑（SP）对大脑皮层的渐进性侵袭，以及神经元和突触丧失的程度。在非典型AD中，在语言、运动能力、额叶和执行能力或视觉空间技能方面会出现明显且早期的缺陷。这些非典型临床特征与NFT或SP形成的异常模式相关，这种模式主要涉及在退行性过程中通常未受影响的皮质区域。为了对这个高度异质性的亚组进行分类，本文概述了AD症状非典型进展患者的临床病理分析，特别提及了特定认知和行为缺陷与大脑皮层内AD病变分布层次模式之间的关系。基于这些以皮质回路为基础探索导致AD神经心理学表现机制的代表性实例，我们还批判性地讨论了建立一个将该疾病的临床表现与前向和后向长皮质皮质通路退化相联系的矩阵的可能性。
