To identify and quantify changes among presymptomatic Huntington disease gene carriers who had not yet developed definite chorea, we performed the largest, study of individuals at-risk for HD (n=657) Subtle abnormalities in oculomotor, extrapyramidal and pyramidal motor, and cognitive measures were identified. We propose to reexamine this unique sample of at-risk individuals using an expanded test battery that includes more sensitive and specific quantitative measures for each subset of variables for which significant differences between presymptomatic gene carriers and nongene carriers were initially observed. These new measures increase the power of our proposed longitudinal studies of the rate of change among presymptomatic gene carriers as they approach the manifestation of clinically diagnosable HD. These novel studies are designed to: 1) Further delineate the deficits observed in the subclinical and early symptomatic phase of disease; 2) measure the rate of increasing abnormality among presymptomatic gene carriers; 3) investigate the interrelationships among the variables so as to identify measures with similar rates of deterioration, which might suggest common pathways affected early in the disease process; 4) quantify the relationship of CAG repeat number with disease onset and progression. The results of these studies will improve the understanding of the presymptomatic and early symptomatic phase of HD allowing for earlier diagnosis and identify subclinical biomarkers that can be utilized in clinical trials to evaluate therapeutic agents designed to slow progression and delay the onset of clinical HD.
| Rupp, Jason; Dzemidzic, Mario; Blekher, Tanya et al. (2012) Comparison of vertical and horizontal saccade measures and their relation to gray matter changes in premanifest and manifest Huntington disease. J Neurol 259:267-76 |
| Rupp, Jason; Dzemidzic, Mario; Blekher, Tanya et al. (2011) Abnormal error-related antisaccade activation in premanifest and early manifest Huntington disease. Neuropsychology 25:306-18 |
| Rupp, Jason; Blekher, Tanya; Jackson, Jacqueline et al. (2010) Progression in prediagnostic Huntington disease. J Neurol Neurosurg Psychiatry 81:379-84 |
| Blekher, Tanya; Weaver, Marjorie R; Marshall, Jeanine et al. (2009) Visual scanning and cognitive performance in prediagnostic and early-stage Huntington's disease. Mov Disord 24:533-40 |
| Blekher, Tanya; Weaver, Marjorie R; Cai, Xueya et al. (2009) Test-retest reliability of saccadic measures in subjects at risk for Huntington disease. Invest Ophthalmol Vis Sci 50:5707-11 |
| Blekher, Tanya; Weaver, Marjorie; Rupp, Jason et al. (2009) Multiple step pattern as a biomarker in Parkinson disease. Parkinsonism Relat Disord 15:506-10 |
| O'Donnell, Brian F; Blekher, Tanya M; Weaver, Marjorie et al. (2008) Visual perception in prediagnostic and early stage Huntington's disease. J Int Neuropsychol Soc 14:446-53 |
| Solomon, Andrea C; Stout, Julie C; Weaver, Marjorie et al. (2008) Ten-year rate of longitudinal change in neurocognitive and motor function in prediagnosis Huntington disease. Mov Disord 23:1830-6 |
| Marshall, Jeanine; White, Kerry; Weaver, Marjorie et al. (2007) Specific psychiatric manifestations among preclinical Huntington disease mutation carriers. Arch Neurol 64:116-21 |
| Stout, Julie C; Weaver, Marjorie; Solomon, Andrea C et al. (2007) Are cognitive changes progressive in prediagnostic HD? Cogn Behav Neurol 20:212-8 |
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