| 1. |
- Baker, Chaya Rochel, et al.
(författare)
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Subjective sleep problems in Huntington's disease : A pilot investigation of the relationship to brain structure, neurocognitive, and neuropsychiatric function
- 2016
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 364, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- Subjective reports of sleep disturbance are a common feature of Huntington's disease (HD); however, there is limited research investigating the relationship between sleep problems with changes in brain and behaviour. This study aimed to investigate whether subjective reports of sleep problems in HD are associated with brain volume, neurocognitive decline, and neuropsychiatric symptoms. This retrospective pilot study used brain volume, neurocognitive and neuropsychiatric data from premanifest (pre-HD) and symptomatic HD (symp-HD). Subjective sleep problem was measured using the sleep item of the Beck's Depression Inventory-II (BDI-II). Pre-HD individuals reporting sleep problems had significantly poorer neuropsychiatric outcomes compared to those not reporting sleep problems. In the symp-HD group, those with sleep problems had significantly accelerated thalamic degeneration and poorer neuropsychiatric outcomes compared to those without sleep problems. There was no relationship between subjective sleep problems and neurocognitive measures. These findings suggest an association between subjective sleep disturbance, neuropathology, and development of neuropsychiatric symptoms in HD. Further studies using quantitative EEG-based monitoring of sleep in HD and changes in the brain and behaviour will be necessary to establish the causal nature of this relationship.
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| 2. |
- Gabery, Sanaz, et al.
(författare)
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Early white matter pathology in the fornix of the limbic system in Huntington disease
- 2021
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 142:5, s. 791-806
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. The typical motor symptoms have been associated with basal ganglia pathology. However, psychiatric and cognitive symptoms often precede the motor component and may be due to changes in the limbic system. Recent work has indicated pathology in the hypothalamus in HD but other parts of the limbic system have not been extensively studied. Emerging evidence suggests that changes in HD also include white matter pathology. Here we investigated if the main white matter tract of the limbic system, the fornix, is affected in HD. We demonstrate that the fornix is 34% smaller already in prodromal HD and 41% smaller in manifest HD compared to controls using volumetric analyses of MRI of the IMAGE-HD study. In post-mortem fornix tissue from HD cases, we confirm the smaller fornix volume in HD which is accompanied by signs of myelin breakdown and reduced levels of the transcription factor myelin regulating factor but detect no loss of oligodendrocytes. Further analyses using RNA-sequencing demonstrate downregulation of oligodendrocyte identity markers in the fornix of HD cases. Analysis of differentially expressed genes based on transcription-factor/target-gene interactions also revealed enrichment for binding sites of SUZ12 and EZH2, components of the Polycomb Repressive Complex 2, as well as RE1 Regulation Transcription Factor. Taken together, our data show that there is early white matter pathology of the fornix in the limbic system in HD likely due to a combination of reduction in oligodendrocyte genes and myelin break down.
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| 3. |
- Gabery, Sanaz, et al.
(författare)
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Volumetric analysis of the hypothalamus in Huntington Disease using 3T MRI: the IMAGE-HD Study.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Non-motor symptoms and signs such as psychiatric disturbances, sleep problems and metabolic dysfunction are part of the disease manifestation. These aspects may relate to changes in the hypothalamus, an area of the brain involved in the regulation of emotion, sleep and metabolism. Neuropathological and imaging studies using both voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) as well as positron emission tomography (PET) have demonstrated pathological changes in the hypothalamic region during early stages in symptomatic HD. In this investigation, we aimed to establish a robust method for measurements of the hypothalamic volume in MRI in order to determine whether the hypothalamic dysfunction in HD is associated with the volume of this region. Using T1-weighted imaging, we describe a reproducible delineation procedure to estimate the hypothalamic volume which was based on the same landmarks used in histologically processed postmortem hypothalamic tissue. Participants included 36 prodromal HD (pre-HD), 33 symptomatic HD (symp-HD) and 33 control participants who underwent MRI scanning at baseline and 18 months follow-up as part of the IMAGE-HD study. We found no evidence of cross-sectional or longitudinal changes between groups in hypothalamic volume. Our results suggest that hypothalamic pathology in HD is not associated with volume changes.
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| 4. |
- Looi, Jeffrey C. L., et al.
(författare)
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The Australian, US, Scandinavian Imaging Exchange (AUSSIE): an innovative, virtually-integrated health research network embedded in health care
- 2014
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Ingår i: Australasian Psychiatry. - : SAGE Publications. - 1039-8562 .- 1440-1665. ; 22:3, s. 260-265
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the development, design and function of an innovative international clinical research network for neuroimaging research, based in Australia, within a joint state health service/medical school. This Australian, US, Scandinavian Imaging Exchange (AUSSIE) network focuses upon identifying neuroimaging biomarkers for neuropsychiatric and neurodegenerative disease. Methods: We describe a case study of the iterative development of the network, identifying characteristic features and methods which may serve as potential models for virtual clinical research networks. This network was established to analyse clinically-derived neuroimaging data relevant to neuropsychiatric and neurodegenerative disease, specifically in relation to subcortical brain structures. Results: The AUSSIE network has harnessed synergies from the individual expertise of the component groups, primarily clinical neuroscience researchers, to analyse a variety of clinical data. Conclusion: AUSSIE is an active virtual clinical research network, analogous to a connectome, which is embedded in health care and has produced significant research, advancing our understanding of neuropsychiatric and neurodegenerative disease through the lens of neuroimaging.
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