Los complejos de las demencias degenerativas: una evolución de la enfermedad al espectro

Introduction. 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 «complexes» (groups of entities with symptomatic, neurochemical, histopathologic and proteinopathic affinities). Method. 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). Results. 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. Conclusions. 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.