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

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

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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.

Original language	English
Article number	116522
Journal	Journal of the Neurological Sciences
Volume	408
Early online date	13 Oct 2019
DOIs	https://doi.org/10.1016/j.jns.2019.116522
Publication status	Published - 15 Jan 2020

Keywords

Brain-derived neurotrophic factor
Circadian rhythm
Cortisol
DEFICITS
ENVIRONMENTAL ENRICHMENT
EXERCISE
Hypothalamus
MELATONIN
Melatonin
NEUROGENESIS
NEUROTROPHIC FACTOR BDNF
PARKINSONS
PERIODIZATION
SLEEP-WAKE CYCLE
Sleep
TRANSGENIC MOUSE MODEL

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10.1016/j.jns.2019.116522

Accepted_ManuscriptAccepted author manuscript, 692 KBLicence: CC BY-NC-ND

https://linkinghub.elsevier.com/retrieve/pii/S0022510X1930454X

Cite this

Bartlett, D. M., Dominguez D, J. F., Lazar, A. S., Kordsachia, C. C., Rankin, T. J., Lo, J., Govus, A. D., Power, B. D., Lampit, A., Eastwood, P. R., Ziman, M. R., & Cruickshank, T. M. (2020). Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study. Journal of the Neurological Sciences, 408, [116522]. https://doi.org/10.1016/j.jns.2019.116522

@article{02ecf04afb824b129074c51df791c1c7,

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

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, DEFICITS, ENVIRONMENTAL ENRICHMENT, EXERCISE, Hypothalamus, MELATONIN, Melatonin, NEUROGENESIS, NEUROTROPHIC FACTOR BDNF, PARKINSONS, PERIODIZATION, SLEEP-WAKE CYCLE, Sleep, TRANSGENIC MOUSE MODEL",

author = "Bartlett, {Danielle M.} and {Dominguez D}, {Juan F.} and Lazar, {Alpar S.} and Kordsachia, {Catarina C.} and Rankin, {Tim J.} and Johnny Lo and Govus, {Andrew D.} and Power, {Brian D.} and Amit Lampit and Eastwood, {Peter R.} and Ziman, {Mel R.} and Cruickshank, {Travis M.}",

year = "2020",

month = jan,

day = "15",

doi = "10.1016/j.jns.2019.116522",

language = "English",

volume = "408",

journal = "Journal of the Neurological Sciences",

issn = "0022-510X",

publisher = "Elsevier",

}

Bartlett, DM, Dominguez D, JF, Lazar, AS, Kordsachia, CC, Rankin, TJ, Lo, J, Govus, AD, Power, BD, Lampit, A, Eastwood, PR, Ziman, MR & Cruickshank, TM 2020, 'Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study', Journal of the Neurological Sciences, vol. 408, 116522. https://doi.org/10.1016/j.jns.2019.116522

TY - JOUR

T1 - Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study

AU - Bartlett, Danielle M.

AU - Dominguez D, Juan F.

AU - Lazar, Alpar S.

AU - Kordsachia, Catarina C.

AU - Rankin, Tim J.

AU - Lo, Johnny

AU - Govus, Andrew D.

AU - Power, Brian D.

AU - Lampit, Amit

AU - Eastwood, Peter R.

AU - Ziman, Mel R.

AU - Cruickshank, Travis M.

PY - 2020/1/15

Y1 - 2020/1/15

N2 - 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.

AB - 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.

KW - Brain-derived neurotrophic factor

KW - Circadian rhythm

KW - Cortisol

KW - DEFICITS

KW - ENVIRONMENTAL ENRICHMENT

KW - EXERCISE

KW - Hypothalamus

KW - MELATONIN

KW - Melatonin

KW - NEUROGENESIS

KW - NEUROTROPHIC FACTOR BDNF

KW - PARKINSONS

KW - PERIODIZATION

KW - SLEEP-WAKE CYCLE

KW - Sleep

KW - TRANSGENIC MOUSE MODEL

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U2 - 10.1016/j.jns.2019.116522

DO - 10.1016/j.jns.2019.116522

M3 - Article

VL - 408

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

M1 - 116522

ER -

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

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Alpar Lazar

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

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Alpar Lazar

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