Cognition-oriented treatments and physical exercise on cognitive function in Huntington’s disease: protocol for systematic review

Abstract

Introduction

Cognitive impairments are prevalent in Huntington’s disease (HD), occurring many years prior to clinical diagnosis and are the most impactful on quality of life. Cognitive interventions and exercise have been found to be efficacious in improving cognitive function in several clinical populations (e.g. older adults with mild cognitive impairment and dementia). However, the utility of cognitive interventions has not been systematically reviewed in HD. This systematic review aims to examine the efficacy of cognitive and physical interventions on cognitive function in HD.

Methods

Electronic databases (MEDLINE, EMBASE, PsycINFO, CENTRAL) were searched from inception until 10 May 2021 for interventional studies investigating the effect of cognition-oriented treatments and physical exercise on cognitive function in individuals with HD, compared to any control or no control. The primary outcome is change on objective measures of cognition. Additional outcomes include change in psychosocial, functional and neuroimaging measures. Variations of effects based on population and study factors will be considered. Risk of bias will be assessed using the Cochrane RoB 2 tool and ROBINS-I tool. Where appropriate, outcomes will be pooled using random-effects meta-analyses, heterogeneity will be examined using tau² and I² statistics, and moderators will be examined using meta-regression models.

Discussion

This review will systematically evaluate the efficacy of cognitive and physical interventions on improving cognitive function in HD. The eligibility criteria and planned analyses will allow for a comprehensive assessment of certainty in the evidence that will inform future trials and clinical practice.

Registration

This protocol was registered on PROSPERO (CRD42021259152).

Keywords:

• Systematic review
• Huntington disease
• cognition
• cognitive intervention
• physical exercise

Disclosure statement

The authors have no conflicts of interest to declare.

Data availability statement

Data sharing is not applicable to this manuscript as no new data were created or analyzed.

Contributions

KH led the design of the review and the drafting of the manuscript, LN edited the draft manuscript, SJ edited the draft manuscript, NGK contributed to the design of the review and edited the draft manuscript, AL contributed to the design of the review and edited the draft manuscript.

Additional information

Funding

No funding was acquired for this manuscript. Jamadar is supported by an Australian National Health and Medical Research Council (NHMRC) Fellowship (APP1174164).

Notes on contributors

Katharine Huynh

Katharine Huynh is a PhD candidate at Monash University, Australia, supported by the Australian Government Research Training Program Stipend Scholarship. Her research examines non-pharmacological interventions and neuroimaging biomarkers in populations with cognitive impairment and dementia. She completed a Bachelor of Psychology (Hons Class I with University Medal) at the University of Sydney, Australia, where she used neuroimaging to characterise white matter hyperintensities in patients with frontotemporal dementia and Alzheimer’s disease.

Leila Nategh

Leila Nategh is a PhD candidate at the University of Melbourne, Australia, supported by an International PhD Scholarship. Her research focuses on cognitive interventions in patients with cognitive impairment. She completed a master’s degree in Cognitive Rehabilitation at Shahid Beheshti University, Iran, where she compared the impact of two different cognitive interventions (memory or attention) on episodic memory in patients at the onset of Alzheimer's disease.

Sharna Jamadar

Dr Sharna Jamadar is a Senior Research Fellow and NHMRC Emerging Leader Fellow at Turner Institute for Brain and Mental Health and Monash Biomedical Imaging, Australia. Her research is focused on understanding how life experiences change our brains and may confer resilience to ageing and neuropathology. Sharna is an expert in multimodal neuroimaging and leads the Cognitive Neuroimaging program at Monash Biomedical Imaging, where the team applies MRI and novel simultaneous MRI-PET imaging to understand human brain function. She has received numerous awards for the quality of her research, including the Distinguished Early Career Contribution to Psychopharmacology (Society for Psychophysiological Research, USA).

Nellie Georgiou-Karistianis

Prof Nellie Georgiou-Karistianis is a cognitive neuroscientist and Professor of Psychology. She is currently the Deputy Dean (Academic and Graduate Affairs) in the Faculty of Medicine, Nursing and Health Sciences at Monash University, Victoria, Australia. She heads the Georgiou-Karistianis Experimental Neuropsychology Research Unit within the Turner Institute for Brain and Mental Health. She is internationally renowned for her pioneering work in Huntington’s disease and Friedreich ataxia. She has led large interdisciplinary clinical projects focused on validating neuroimaging biomarkers (IMAGE-HD, IMAGE-FRDA and TRACK-FA), which have attracted funding from competitive government granting schemes and philanthropic bodies.

Amit Lampit

Dr Amit Lampit is a clinical neuroscientist specialising in cognitive training across the lifespan and brain disorders, clinical trials and research synthesis. He is a CR Roper Senior Research Fellow and co-leader of the Cognitive Interventions, Technologies and Evaluation Group at the Academic Unit for Psychiatry of Old Age, University of Melbourne, Australia. In addition to co-leading CITE, he is an assistant director of evidence synthesis at the National Disability Insurance Agency, and an affiliated researcher for the Biostatistics & Clinical Epidemiology node at the Methods and Implementation Support for Clinical and Health research Hub (MISCH).