Biological indicators of neurodegeneration can be detected in premanifest Huntington's disease gene-mutation carriers. However, preclinical cognitive performance tested with usual instruments generally appears within normal limits in this population. Notably, in the symptomatic stage, the trajectory of cognitive impairment is heterogeneous between patients with equivalent CAG repeat length. We aim to develop: (a) new cognitive measures sensitive to track the earliest cognitive changes occurring in premanifest HD; and (b) cognitive assessment approaches useful to stratify symptomatic patients according to different cognitive profiles. We are also aimed to (c) explore factors other than CAG repeat that may contribute to heterogeneity of neurodegeneration and cognitive impairment and to different trajectories of cognitive progression. For these purposes, we will use multimodal neuroimaging and neurophysiological data to guide and to validate the development of cognitive tasks appropriate to address early cognitive changes in premanifest HD. We will also explore the ability of compiled assessments to stratify symptomatic patients according to different profiles, and explore the possible contribution of TAU pathology to different cognitive phenotypes and neurodegenerative trajectories

Huntington
cognición
tau
biomarcadores
neuroimagen