The contribution of gender differences in motor, behavioral and cognitive features to functional capacity, independence and quality of life in patients with Huntington's disease

https://doi.org/10.1016/j.parkreldis.2018.01.006Get rights and content

Highlights

  • Motor symptoms contribute strongest to function in HD patients.

  • Motor symptoms have stronger impact on functional ability in women than in men with HD.

  • There are no gender differences in functional disability impact on QoL in HD patients.

Abstract

Introduction

Huntington's disease (HD) is a neurodegenerative autosomal dominant disorder affecting patients' motor, behavioral and cognitive domains leading to total dependency for activities of daily life. This study compares whether gender differences in motor, cognitive and behavioral symptoms affect function and how functional impairment affects quality of life (QoL).

Methods

We recruited 2191 subjects from the REGISTRY data base that provides personal data, HD age of onset, visit date, CAG mutation size, UHDRS and TFC scores from at least one visit. For 1166 participants SF-36 was also available. We calculated Spearman coefficients for correlations between particular symptomatic domains and functional scales, Fisher z-transform was used to test whether differences in correlations between genders were statistically significant. Simultaneous linear regression with least-square fit method was used to determine for how much variability in functional scales the particular symptomatic domains are responsible. ANOVA was used to look for QoL differences between TFC-stage based groups. Baseline statistics showed no significant differences between genders.

Results

Motor, cognitive and behavioral domains contributed significantly to function and independence. The motor domain contributed most followed by the cognitive and to a lesser degree by the behavioral domain. Motor symptoms correlated more with functional ability and influenced function variability more in women than in men. The decline in functional abilities correlated significantly with QoL decline.

Conclusion

Motor symptoms have highest impact on function in HD, moreover these symptoms affect female function and independence more than males. Results indicate that symptomatic treatment targeting motor symptoms is needed to improve HD function and QoL.

Introduction

Huntington's disease (HD) is a rare autosomal dominant neurodegenerative progressive disorder affecting patient's motor, behavioral and cognitive domains and leading to dependency in daily life. Currently there is no cure for this disease and mean period from onset to death is 15–20 years [1]. HD conditioned by dynamic mutation of HTT gene at chromosome 4 relies on an extension of CAG trinucleotide repetitive sequence of 36 and higher. It is known that larger CAG repeats expansions are associated with an earlier disease onset and faster disease progression [2]. HD progression is slightly faster in women than in men [3].

A comparative crosscheck on whether and how the three major symptomatic HD domains (i.e. motor, cognitive and behavioral) affect HD patients' functional abilities has yet to be performed. It has been found that particular HD symptoms contribute to functional abilities [4] but these studies were not intended to investigate the impact of 3 HD domains [5]. Exploring this relationship will permit the search for future symptomatic therapies. The development of specific treatment targeting function and independence responsible for the decline in Quality of Life (QoL) is needed as the QoL is related to functional ability [6]. Looking at previously published papers with regard to gender differences in HD progression [3], it is necessary to explore the contribution of gender differences in HD symptoms to the ability to function. It should be also examined whether gender plays a role in the ability to function and QoL. In more common movements disorders e.g. Parkinson's disease (PD), several studies have explored how motor and non-motor symptoms contribute to the ability to function and QoL [[7], [8], [9], [10], [11], [12]]. Results of these studies are often controversial but psychiatric disturbances particularly depression appear to have a negative impact on the ability to function and QoL in PD [12].

Section snippets

Aim of the study

The purpose of this study was to compare how symptoms of the three major HD domains: motor cognitive and behavioral, measured using the Unified Huntington's Disease Rating Scale (UHDRS), contribute to function and independence, measured in UHDRS Functional Assessment and Total Functional Capacity (TFC), in men and in women, and how they affect QoL.

Data

Patients' data from the REGISTRY database were used. REGISTRY is a longitudinal, observational, multicentre, European study on clinical phenomenology and course of HD [13]. To assess the patients for the purpose of REGISTRY the motor, functional, cognitive, independence and TFC scales of the UHDRS were used [14]. In the UHDRS higher scores on motor and behavioral scales indicate worse symptoms, while higher scores on the cognitive scale indicate better cognitive function and higher scores on

Basic descriptive statistics

Descriptive statistics are given in Table 1. No significant differences were observed between men and women in age at first visit, age of onset, disease duration or the number of CAG triplets expansion in the larger alleles. In UHDRS motor, functional, independence scales scores, and TFC scores differences between genders were significant women being the more affected.

Contribution of the UHDRS motor, cognitive and behavioral scores on function

We found all analyzed correlations between scales measuring patient's intensity of symptoms with functional abilities to be

Discussion

Our results suggest a clear and strong contribution of each HD symptom domain to a decline in function and independence. Motor symptoms affected the individuals' ability to function more than other domains. This finding is in agreement with previous studies the results of which emphasize a correlation between function and motor symptoms [19] e.g. bradykinesia [20] and/or hypokinetic HD clinical picture [21]. There is a link between less choreatic HD phenotype, worse cognitive performance and

Conclusion

In conclusion, our analysis points out the urgency to put major effort into developing treatments to alleviate the motor impairment in HD in the attempt to symptomatically improve their QoL, while hoping that one day neuroprotective therapies will provide a cure. As it is a second study where gender differences in HD have been confirmed, it is important to take gender into account when proposing future clinical trials and look into genetic aspect of gender contribution to HD clinical picture.

Funding

This research received no funding from agencies in the public, commercial, or not-for-profit sectors.

Conflicts of interest

The authors report no conflict of interest.

Acknowledgements

We thank Sue Calne for RN CM for editing assistance. We thank all patients of this study. We thank all patients and their families who collaborated with the Italian League for Research on Huntington and related diseases (www.lirh.it).

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