Concomitant pathologies and their impact on Huntington's disease. A brief review of current evidence.

Accumulating evidence not only highlights the role of mixed proteinopathies (phosphorylated tau, α-synuclein and TDP-43) in the pathological process and clinical expression of Huntington’s disease (HD), but also points to the presence of multiple comorbidities. HD is a complex disease that is frequently associated with other disorders, in particular diabetes mellitus, cholesterol and lipid mismetabolism, hypertension, neurovascular, cardiovascular and cerebrovascular pathologies, amylotrophic lateral sclerosis and a small number of other neurodegenerative processes. Controversies exist concerning the inverse comorbidity of HD and cancer. The heterogeneity of concomitant pathologies and comorbidities observed along the HD spectrum that impair the quality of life of the patients is most likely caused by a complex interplay between genetic, pathogenetic and other risk factors that need further elucidation. All these concomitant disorders have an impact on the clinical features, course, and prognosis of HD. Further research should provide not only better insight into the epidemiology of co-pathologies and comorbidities, but in particular into their relationship with HD in order to find better diagnostic tools and probable therapies for the comorbidities that complicate the course of HD.