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

ABSTRACT:

Background

There 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.

Methods

Fifteen 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.

Results

Participants 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.

Conclusions

This 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.

SUBMITTER: Cruickshank TM

PROVIDER: S-EPMC4309878 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Studies of physical therapy and multidisciplinary rehabilitation programs for Huntington's disease (HD) have shown improvements in gait function, balance, and physical quality of life. There is a gap in the literature on effects of cognitive interventions and the potential to improve cognitive performance. OBJECTIVE:To assess changes in cognitive performance among patients with early to middle stage HD as secondary analyses from a one-year multidisciplinary rehabilitation program. The program included cognitive stimulation as a non-specific cognitive intervention in addition to physical interventions. METHODS:A one-year rehabilitation program that included comprehensive neuropsychological assessments was completed by 31 out 37 participants with early to middle stages of HD. Socio-demographic and clinical information was recorded. A battery of neuropsychological tests was used to measure cognitive functions before and after the intervention. Descriptive statistics was used for sample characteristics. Paired sample t-tests and nonparametric Wilcoxon Signed ranked tests were used to compare cognitive measures at both time points. RESULTS:Scores on the Symbol Digit Modalities Test (SDMT) were significantly lower post intervention. There were no significant differences in all other measures. Scores on the Stroop color naming and California Verbal Learning Test-II (CVLT-II) long-term delayed recall tasks showed tendencies towards lower scores post intervention. CONCLUSIONS:An intensive multidisciplinary rehabilitation program for patients with HD was generally well tolerated and feasible, with no indication of negative effects on cognition. Neuropsychological measures overall remained stable following an intensive multidisciplinary rehabilitation program, however continued progression of cognitive impairment was evident on the SDMT, suggesting that disease progression is not halted. Randomized controlled trials are needed to verify these findings.

Project description:An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington's disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington's disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington's disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington's disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington's disease and their effect on brain structure.