Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study

Danielle M Bartlett; Juan F Dominguez D; Alpar S Lazar; Catarina C Kordsachia; Tim J Rankin; Johnny Lo; Andrew D Govus; Brian D Power; Amit Lampit; Peter R Eastwood; Mel R Ziman; Travis M Cruickshank

doi:10.1016/j.jns.2019.116522

Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study

J Neurol Sci. 2020 Jan 15:408:116522. doi: 10.1016/j.jns.2019.116522. Epub 2019 Oct 13.

Authors

Affiliations

¹ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia. Electronic address: d.bartlett@ecu.edu.au.
² Cognition and Emotion Research Centre & Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.
³ Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, Norfolk, United Kingdom.
⁴ Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
⁵ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
⁶ School of Science, Edith Cowan University, Joondalup, Western Australia, Australia.
⁷ School of Allied Health, Department of Human Services, Nutrition and Sport, La Trobe University, Melbourne, Victoria, Australia.
⁸ School of Medicine, The University of Notre Dame, Fremantle, Western Australia, Australia.
⁹ Department of Psychiatry, University of Melbourne, Victoria, Australia; Department of Neurology, Charité - Universitätsmedizin Berlin, Germany.
¹⁰ Centre for Sleep Science, School of Human Sciences, Faculty of Science, University of Western Australia, Crawley, Western Australia, Australia.
¹¹ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; School of Biomedical Science, University of Western Australia, Crawley, Western Australia, Australia.
¹² Exercise Medicine Research Institute, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; Perron Institute for Neurological and Translational Science, Perth, Western Australia, Australia.

PMID: 31665619
DOI: 10.1016/j.jns.2019.116522

Abstract

Background: Hypothalamic pathology is a well-documented feature of Huntington's disease (HD) and is believed to contribute to circadian rhythm and habitual sleep disturbances. Currently, no therapies exist to combat hypothalamic changes, nor circadian rhythm and habitual sleep disturbances in HD.

Objective: To evaluate the effects of multidisciplinary rehabilitation on hypothalamic volume, brain-derived neurotrophic factor (BDNF), circadian rhythm and habitual sleep in individuals with preclinical HD.

Methods: Eighteen individuals with HD (ten premanifest and eight prodromal) undertook a nine-month multidisciplinary rehabilitation intervention (intervention group), which included exercise, cognitive and dual task training and social events, and were compared to a community sample of eleven individuals with premanifest HD receiving no intervention (control group). Hypothalamic volume, serum BDNF, salivary cortisol and melatonin concentrations, subjective sleep quality, daytime somnolence, habitual sleep-wake patterns, stress and anxiety and depression symptomatology were evaluated.

Results: Hypothalamus grey matter volume loss was significantly attenuated in the intervention group compared to the control group after controlling for age, gender, Unified Huntington's Disease Rating Scale-Total Motor Score and number of cytosine-adenine-guanine repeats. Serum BDNF levels were maintained in the intervention group, but decreased in the control group following the study period. Both groups exhibited decreases in cortisol and melatonin concentrations. No changes were observed in sleep or mood outcomes.

Conclusions: This exploratory study provides evidence that multidisciplinary rehabilitation can reduce hypothalamic volume loss and maintain peripheral BDNF levels in individuals with preclinical HD but may not impact on circadian rhythm. Larger, randomised controlled trials are required to confirm these findings.

Keywords: Brain-derived neurotrophic factor; Circadian rhythm; Cortisol; Hypothalamus; Melatonin; Sleep.

Publication types

Controlled Clinical Trial

MeSH terms

Adult
Brain-Derived Neurotrophic Factor* / blood
Circadian Rhythm / physiology
Female
Follow-Up Studies
Gray Matter / diagnostic imaging*
Gray Matter / physiology
Humans
Huntington Disease / blood
Huntington Disease / diagnostic imaging*
Huntington Disease / rehabilitation*
Hypothalamus / diagnostic imaging*
Hypothalamus / physiology
Male
Middle Aged
Organ Size
Pilot Projects
Prodromal Symptoms*
Sleep / physiology
Time Factors

Substances

Brain-Derived Neurotrophic Factor
BDNF protein, human