Journal article
Thalamic metabolism and symptom onset in preclinical Huntington's disease
Brain (London, England : 1878), Vol.130(11), pp.2858-2867
11/2007
DOI: 10.1093/brain/awm217
PMCID: PMC4455546
PMID: 17893097
Abstract
The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P < 0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P < 0.003) but declined at 44 months (P < 0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P < 0.01). Striatal metabolism was abnormally low at all time points (P < 0.005). By contrast, thalamic metabolism was elevated at baseline (P < 0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.
Details
- Title: Subtitle
- Thalamic metabolism and symptom onset in preclinical Huntington's disease
- Creators
- A Feigin - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USAC Tang - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USAY Ma - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USAP Mattis - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USAD Zgaljardic - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USAM Guttman - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USAJ. S Paulsen - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USAV Dhawan - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USAD Eidelberg - Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neurology, North Shore University Hospital and New York University School of Medicine, New York, Department of Psychiatry, North Shore-Long Island Jewish Health System, Manhasset, NY, Department of Neuropsychology, Transitional Learning Centre, Galveston, TX, USA, Department of Neurology, University of Toronto, Toronto, Canada and Department of Neurology, University of Iowa, Des Moines, IA, USA
- Resource Type
- Journal article
- Publication Details
- Brain (London, England : 1878), Vol.130(11), pp.2858-2867
- Publisher
- Oxford University Press
- DOI
- 10.1093/brain/awm217
- PMID
- 17893097
- PMCID
- PMC4455546
- ISSN
- 0006-8950
- eISSN
- 1460-2156
- Language
- English
- Date published
- 11/2007
- Academic Unit
- Psychiatry; Psychological and Brain Sciences
- Record Identifier
- 9984083225902771
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