Randomized, Single-blind Clinical Trial to Evaluate the Efficacy of Cognitive Rehabilitation Using Inmersive Virtual Reality and Computer-based Cognitive Stimulation Versus Music Therapy on Cognitive Impairment Associated With Movement Disorders

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive neuronal loss in the substantia nigra of the midbrain, as well as in other areas such as the pons, diencephalon, limbic system, and temporal cortex, which is accompanied by the deposition of alpha-synuclein in surviving neurons. (1) This neurodegeneration clinically manifests as motor symptoms (bradykinesia, rigidity, tremor) and non-motor symptoms (depression, anxiety, apathy, and cognitive impairment, among others).

Cognitive impairment associated with PD is currently recognized as one of the most relevant non-motor symptoms due to the significant impact it has on families and the economic cost it represents for public health. Dementia associated with PD is invariably preceded by a phase of mild cognitive impairment (MCI), characterized by the presence of alteration in neuropsychological tests without significant impact on the patient's functional capacity. Patients with MCI have a higher risk of developing dementia during the course of the disease. Specifically, conversion rates of 27.8% in the first year and up to 45.5% after 3 years have been described. (2)

Cognitive impairment associated with PD depends both on dopaminergic denervation of the nigrostriatal circuit (and secondary failure of fronto-subcortical circuits) and on the involvement of cholinergic brainstem structures, which project widely in the brain. (3) There is also growing evidence that cognitive impairment in PD is not only related to the deposition of alpha-synuclein, but that the deposition of beta-amyloid (characteristic of Alzheimer's disease) also plays an important role. (4)

Huntington's disease (HD) is a dominant autosomal neurodegenerative disease caused by an expansion of CAG in exon 1 of the gene that encodes for huntingtin on chromosome 4. This abnormal expansion of CAG gives rise to mutant huntingtin, considered the main protein involved in the pathophysiology of HD. (5) Individuals who carry the mutation and have ≥40 CAG repeats will inevitably show progressive motor (chorea, bradykinesia, and dystonia), cognitive (cognitive impairment and dementia), psychiatric (depression, apathy, perseverative behavior, irritability, among others), and functional deterioration in adulthood. The average age of onset of motor symptoms is around 45 years, and the course of the disease is approximately 10-20 years. (6)

Cognitive impairment associated with HD has been mainly attributed to progressive atrophy of the basal ganglia together with the disruption of fronto-subcortical circuits that accompany it. However, other diffuse brain changes, including alterations in cerebral white matter and posterior cortical atrophy, have also been shown to contribute to cognitive impairment. (7, 8)