The effect of multidisciplinary rehabilitation on brain structure and cognition in Huntington's disease: an exploratory study

Abstract

BackgroundThere is a wealth of evidence detailing gray matter degeneration and loss of cognitive function over time in individuals with Huntington's disease (HD). Efforts to attenuate disease-related brain and cognitive changes have been unsuccessful to date. Multidisciplinary rehabilitation, comprising motor and cognitive intervention, has been shown to positively impact on functional capacity, depression, quality of life and some aspects of cognition in individuals with HD. This exploratory study aimed to evaluate, for the first time, whether multidisciplinary rehabilitation can slow further deterioration of disease-related brain changes and related cognitive deficits in individuals with manifest HD.MethodsFifteen participants who manifest HD undertook a multidisciplinary rehabilitation intervention spanning 9 months. The intervention consisted of once-weekly supervised clinical exercise, thrice-weekly self-directed home based exercise and fortnightly occupational therapy. Participants were assessed using MR imaging and validated cognitive measures at baseline and after 9 months.ResultsParticipants displayed significantly increased gray matter volume in the right caudate and bilaterally in the dorsolateral prefrontal cortex after 9 months of multidisciplinary rehabilitation. Volumetric increases in gray matter were accompanied by significant improvements in verbal learning and memory (Hopkins Verbal Learning-Test). A significant association was found between gray matter volume increases in the dorsolateral prefrontal cortex and performance on verbal learning and memory.ConclusionsThis study provides preliminary evidence that multidisciplinary rehabilitation positively impacts on gray matter changes and cognitive functions relating to verbal learning and memory in individuals with manifest HD. Larger controlled trials are required to confirm these preliminary findings.

Neuroendocrine and neurotrophic signaling in Huntington’s disease: Implications for pathogenic mechanisms and treatment strategies

“…Studies evaluating the utility of multidisciplinary therapy have documented significant changes in grey matter volume, as well as improvements in memory, processing speed, balance and gait, mood and quality of life in patients with manifest HD (144)(145)(146)(147). Recent data from our research programme has shown, in particular, that multidisciplinary therapy increases grey matter volume in the caudate tail and dorsolateral PFC in patients with manifest HD (147).…”

“…Recent data from our research programme has shown, in particular, that multidisciplinary therapy increases grey matter volume in the caudate tail and dorsolateral PFC in patients with manifest HD (147). This therapy has also been reported to improve cognitive function, quality of life and depressive symptoms in patients with mild AD and cognitive impairment without dementia (148) and in PD, multidisciplinary therapy has been reported to improve motor performance, dyskinesias, balance and gait and slow disease progression (149)(150)(151).…”

Longitudinal changes in the fronto-striatal network are associated with executive dysfunction and behavioral dysregulation in Huntington's disease: 30 months IMAGE-HD data

“…Psychiatric disturbance is often cited as the most debilitating feature of HD symptomatology with direct implications for functional capacity and quality of life (Hamilton et al, 2003, Duijn et al, 2007. Establishing the underlying functional brain changes associated with the development of psychiatric symptoms is of great importance in the context of identifying target brain regions with functional relevance that could be used for drug development (Katz, 2004, Kozauer andKatz, 2013), new alternative treaments such as stem cell therapy (Maucksch, Vazey, Gordon, & Connor, 2013), multidisciplinary rehabilitation (Cruickshank, et al, 2015), and transcranial magnetic stimulation (Berardelli & Suppa, 2013;Medina & Tunez, 2010).…”

Effects of multidisciplinary therapy on physical function in Huntington's disease

“…5 There are no proven neuroprotective agents for HD and although symptomatic therapies exist, impairments in physical function continue to develop and worsen as the disease progresses. [13][14][15][16][17][18] Such interventions have the capacity to therapeutically address motor and cognitive aspects of the disease, which has been robustly demonstrated in HD mouse models using environmental enrichment. The effects of multidisciplinary therapy interventions, encompassing both physical and cognitive therapy, have been less well studied in patients with HD.…”