The purpose of the proposed Neuroimaging Project is to use quantitative measures from MRI to chart the longitudinal course of atrophy in specific brain structures in patients with Huntington's Disease. In conjunction with Project (Neuropsychology) and Core (Clinical), we will also determine the association between these neuroanatomical changes and longitudinal changes in neuropsychological functioning and clinical symptomatology. We will obtain MRI scans on 150 patients with Huntington's Disease, and on 150 individually matched control subjects. Patients will be scanned every two years using the same standardized MRI protocol. MRI measurements will include volumes of basal ganglia (caudate, putamen, globus pallidus), brain stem, cerebellum, and comparison regions, as well as total gray, white, and CSF volumes, and volumes of specific cortical regions. MRI measures will be correlated and neuropsychological measures obtained at the same visit. We hypothesize that MRI measures of specific brain regions will correlate with specific neuropsychological functions, clinical variables, and length of trinucleotide repeat for the HD patients. Longitudinal changes in MRI measures will also be analyzed. We hypothesize that atrophy in various regions of the brain will progress at different rates during the course of the illness. We also hypothesize that rate of atrophy in specific brain regions will be correlated with rate of decline in specific neuropsychological functions. This project will provide the first systematic view of atrophy in several specific brain regions within the same HD patients over time. By comparing decline in specific neuropsychological functions and clinical symptoms with atrophy in specific regions that may deteriorate at different rates and at different points during the course of the illness, we will be able to provide a more complete picture of brain-behavior relationships in HD.

Project Start
1998-01-01
Project End
1998-12-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
18
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Faria, Andreia V; Ratnanather, J Tilak; Tward, Daniel J et al. (2016) Linking white matter and deep gray matter alterations in premanifest Huntington disease. Neuroimage Clin 11:450-460
Krause, Amanda; Mitchell, Claire; Essop, Fahmida et al. (2015) Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype. Am J Med Genet B Neuropsychiatr Genet 168:573-85
Ross, Christopher A; Pantelyat, Alex; Kogan, Jane et al. (2014) Determinants of functional disability in Huntington's disease: role of cognitive and motor dysfunction. Mov Disord 29:1351-8
Hua, Jun; Unschuld, Paul G; Margolis, Russell L et al. (2014) Elevated arteriolar cerebral blood volume in prodromal Huntington's disease. Mov Disord 29:396-401
Unschuld, Paul G; Liu, Xinyang; Shanahan, Megan et al. (2013) Prefrontal executive function associated coupling relates to Huntington's disease stage. Cortex 49:2661-73
Unschuld, Paul G; Edden, Richard A E; Carass, Aaron et al. (2012) Brain metabolite alterations and cognitive dysfunction in early Huntington's disease. Mov Disord 27:895-902
Guo, Zhihong; Rudow, Gay; Pletnikova, Olga et al. (2012) Striatal neuronal loss correlates with clinical motor impairment in Huntington's disease. Mov Disord 27:1379-86
Fu, Jinrong; Jin, Jing; Cichewicz, Robert H et al. (2012) trans-(-)-?-Viniferin increases mitochondrial sirtuin 3 (SIRT3), activates AMP-activated protein kinase (AMPK), and protects cells in models of Huntington Disease. J Biol Chem 287:24460-72
Rosenblatt, Adam; Kumar, Brahma V; Mo, Alisa et al. (2012) Age, CAG repeat length, and clinical progression in Huntington's disease. Mov Disord 27:272-6
Ratovitski, Tamara; Chighladze, Ekaterine; Arbez, Nicolas et al. (2012) Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis. Cell Cycle 11:2006-21

Showing the most recent 10 out of 55 publications