Leisure Time Helps Preserve Cognition, Function in Early Huntington’s

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by Marta Figueiredo PhD |

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Spending more time on leisure activities — which contributes to a person’s cognitive reserve, or the ability to improvise — is associated with lesser cognitive and functional decline in people with early manifest Huntington’s disease, a study shows.

In addition, a greater number of CAG repeats within the HTT gene — the genetic cause of Huntington’s — was significantly associated with a lower cognitive reserve in these patients.

These findings highlight the contribution of both genetic and environmental factors on the development and progression of Huntington’s, and suggest that cognitive reserve, particularly in relation to leisure time, may be a therapeutic target in this patient population, the researchers noted.

Still, future, larger studies are needed to confirm these findings.

The study, “Cognitive Reserve in Early Manifest Huntington Disease Patients: Leisure Time Is Associated with Lower Cognitive and Functional Impairment,” was published in the Journal of Personalized Medicine.

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Cognitive reserve is the adult brain’s ability to cope with neurodegenerative processes by improvising and finding alternative ways of performing a task, thereby sustaining greater nerve cell damage before developing cognitive symptoms.

It is thought to be the result of innate intelligence or life experiences, such as education, occupation, and leisure activities.

Increasing evidence shows an association between higher cognitive reserve and better cognitive and clinical performance among people with several neurological conditions, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.

However, its effects in Huntington’s disease remain largely unclear.

To address this, a team of researchers in Italy analyzed the cognitive reserve and clinical data of 75 adults — 47 men and 28 women — with early manifest Huntington’s. All were recruited from three Italian sites involved in the long-term global Enroll-HD observational study (NCT01574053), underway at 178 locations worldwide.

Cognitive reserve was evaluated with the Cognitive Reserve Index questionnaire, a validated scale that includes three sections: education, working activity, and leisure time. The total score and the three sub-scores were considered in the analysis.

Clinical outcomes were quantified at the study’s start, and after one and two years, using the Total Functional Capacity Score and the Unified Huntington’s Disease Rating Scale (UHDRS), which assesses motor, cognitive, functional, and behavioral changes. Cognitive function also was assessed through several validated measures.

The patients’ mean age at the study’s start was 47.2, ranging from 27 to 78 years. They carried between 40 and 49 CAG repeats — with 40 or more being associated with Huntington’s — and developed motor symptoms at a mean age of 47.5 years. The mean number of school years completed was 11.7, with a range of 8 to 18 years.

Results showed that leisure time had a significant impact on functional and cognitive decline over time, but not on motor changes.

The group of 51 patients with normal leisure time scores showed significantly better cognitive and multidimensional (UHDRS) performance at the study’s start relative to the group of 24 patients with lower-than-normal leisure time scores.

Spending less time doing leisure activities also was significantly associated with greater cognitive, functional, and multidimensional decline over time, highlighting the beneficial effect of leisure activities on Huntington’s progression.

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These findings, consistent with previous studies in neurodegenerative diseases other than Huntington’s, indicate that leisure activities “contribute to increment a specific cognitive reserve that modulates the negative effect of brain [damage] on cognition and independence in daily life,” the researchers wrote.

Notably, total cognitive reserve was significantly associated with changes in some cognitive measures over time, suggesting “a possible, although marginal influence of other CR [cognitive reserve] variables on global cognitive deterioration over time,” the team wrote.

Moreover, cognitive reserve was found to be significantly associated with the number of CAG repeats in the HTT gene, with patients carrying more repeats showing poorer cognitive reserve.

However, the number of CAG repeats did not affect the association between leisure time and clinical or cognitive outcomes, which may be explained by the relatively similar number of repeats between included patients, the team noted.

Larger studies including patients “carrying higher repeat expansions (i.e., large mutations beyond 50 CAG repeats affecting young patients) may eventually highlight such a neurobiological effect of the mutation,” the researchers wrote.

“Our findings support the interesting hypothesis that in addition to possible genetic modifiers, the environment may consistently contribute to disease course modification and may represent a therapeutic target,” the team wrote.

Particularly, they suggest that “increased leisure time lowers [Huntington’s] progression as measured by functional and multidimensional variables, with more preserved cognitive status over time,” they added.

Should these results be confirmed in larger studies, they could be used to direct Huntington’s patients to specific cognitive training programs and to recruit patients of all levels of cognitive reserve into clinical trials, the team concluded.