Robles Alfredo
Unidad de Neurología Cognitiva, Hospital La Rosaleda, Santiago de Compostela (A Coruña).
Neurologia. 2009 Jul-Aug;24(6):399-418.
Everyone has a particular combination of risk polymorphisms and occasionally determinant mutations, related to molecular items which are pathogenetic in degenerative dementias. If we add other epigenetic factors to this, we can generate a very heterogeneous base, which explains why these diseases manifest through varied clinical and neuropathological phenotypes, distributed in <
A review of the current knowledge about phenotype variants of degenerative dementias has been carried out, detecting overlapping and divergent aspects between them and generating groups (complexes) which are more operative to work with, instead of using the current independent entities (diseases).
Besides the known Pick complex, there are sufficient data to propose the recognition of the Lewy complex, Alzheimer complex, multisystemic atrophy complex, and polyglutamine complex. Each one of them contains phenotypic variants that overlap with other complex variants, creating links between all the complexes and forming a spectrum in which almost all degenerative dementias can be included.
The progression of medical knowledge has made it more appropriate to locate each patient at a specific point in a complex, in the degenerative dementia spectrum, instead of diagnosing a generic disease. This change makes it recommendable to adjust the diagnostic criteria, and the therapeutic decisions should be designed individually according to their specific location in a complex. Researchers should also take into account this diversity when establishing both the criteria for selecting participants and the objectives of their therapeutic trials.
每个人都有特定的风险多态性组合,偶尔还有决定性突变,这些与神经退行性痴呆的致病分子因素相关。如果再加上其他表观遗传因素,我们就能产生一个非常异质的基础,这就解释了为什么这些疾病会通过多样的临床和神经病理表型表现出来,并分布在“复合体”(具有症状、神经化学、组织病理学和蛋白病学关联的实体组)中。
对当前关于神经退行性痴呆表型变异的知识进行了综述,检测它们之间的重叠和差异方面,并生成更便于研究的组(复合体),而不是使用当前独立的实体(疾病)。
除了已知的皮克复合体,有足够的数据支持识别路易体复合体、阿尔茨海默病复合体、多系统萎缩复合体和多聚谷氨酰胺复合体。它们中的每一个都包含与其他复合体变异重叠的表型变异,在所有复合体之间建立联系并形成一个几乎可以涵盖所有神经退行性痴呆的谱系。
医学知识的进步使得将每个患者定位在神经退行性痴呆谱系中某个复合体的特定点上比诊断一种一般性疾病更为合适。这种变化使得调整诊断标准是可取的,并且治疗决策应根据患者在复合体中的具体位置进行个体化设计。研究人员在制定参与者选择标准和治疗试验目标时也应考虑到这种多样性。