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Hippocampal dysfunction defines disease onset in Huntington's disease

Begeti, Faye; Schwab, Laetitia C; Mason, Sarah L and Barker, Roger A LU (2016) In Journal of Neurology, Neurosurgery and Psychiatry 87(9). p.81-975
Abstract

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of frontostriatal networks. However, emerging evidence from animal models of HD suggests that some of the early cognitive deficits may have a hippocampal basis. The objective of this study was to link previous rodent findings in this area to clinical practice.

METHODS: In this study, 94 participants included patients with early HD, premanifest HD and age-matched controls underwent hippocampal-based cognitive assessments. These included a virtual reality version of the Morris water maze, a task involved participants having... (More)

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of frontostriatal networks. However, emerging evidence from animal models of HD suggests that some of the early cognitive deficits may have a hippocampal basis. The objective of this study was to link previous rodent findings in this area to clinical practice.

METHODS: In this study, 94 participants included patients with early HD, premanifest HD and age-matched controls underwent hippocampal-based cognitive assessments. These included a virtual reality version of the Morris water maze, a task involved participants having to swim through a virtual pool to find a submerged platform using a joystick, and the Cambridge Neuropsychological Test Automated Battery (CANTAB) paired associates learning task, a test also known to rely on hippocampal integrity.

RESULTS: Patients with early HD showed impaired performance in both the virtual Morris water maze and the CANTAB paired associates learning. Such deficits were also correlated with estimated years to diagnosis in premanifest participants.

CONCLUSIONS: This study highlights the merit of using analogous tests in the laboratory and clinic and demonstrates that hippocampal impairments are an early feature of HD in patients as previously shown in rodent models of the disease. As such, they could be used not only to assist in the diagnosis of disease onset, but may also be useful as an outcome measure in future therapeutic trials.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Journal Article
in
Journal of Neurology, Neurosurgery and Psychiatry
volume
87
issue
9
pages
7 pages
publisher
BMJ Publishing Group
external identifiers
  • scopus:84958629158
ISSN
1468-330X
DOI
10.1136/jnnp-2015-312413
language
English
LU publication?
no
id
9db466cb-d2c0-4887-925f-ac4ae38e3a5c
date added to LUP
2016-11-23 13:17:39
date last changed
2017-08-06 05:13:55
@article{9db466cb-d2c0-4887-925f-ac4ae38e3a5c,
  abstract     = {<p>BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of frontostriatal networks. However, emerging evidence from animal models of HD suggests that some of the early cognitive deficits may have a hippocampal basis. The objective of this study was to link previous rodent findings in this area to clinical practice.</p><p>METHODS: In this study, 94 participants included patients with early HD, premanifest HD and age-matched controls underwent hippocampal-based cognitive assessments. These included a virtual reality version of the Morris water maze, a task involved participants having to swim through a virtual pool to find a submerged platform using a joystick, and the Cambridge Neuropsychological Test Automated Battery (CANTAB) paired associates learning task, a test also known to rely on hippocampal integrity.</p><p>RESULTS: Patients with early HD showed impaired performance in both the virtual Morris water maze and the CANTAB paired associates learning. Such deficits were also correlated with estimated years to diagnosis in premanifest participants.</p><p>CONCLUSIONS: This study highlights the merit of using analogous tests in the laboratory and clinic and demonstrates that hippocampal impairments are an early feature of HD in patients as previously shown in rodent models of the disease. As such, they could be used not only to assist in the diagnosis of disease onset, but may also be useful as an outcome measure in future therapeutic trials.</p>},
  author       = {Begeti, Faye and Schwab, Laetitia C and Mason, Sarah L and Barker, Roger A},
  issn         = {1468-330X},
  keyword      = {Journal Article},
  language     = {eng},
  number       = {9},
  pages        = {81--975},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Neurology, Neurosurgery and Psychiatry},
  title        = {Hippocampal dysfunction defines disease onset in Huntington's disease},
  url          = {http://dx.doi.org/10.1136/jnnp-2015-312413},
  volume       = {87},
  year         = {2016},
}