Modeling longitudinal change in motor and cognitive processing speed in presymptomatic Huntington's disease

Abstract

Persons who have the genetic mutation responsible for Huntington's disease (HD) have been shown to exhibit lower cognitive test scores years prior to manifest HD. Most studies have examined cognitive performance in presymptomatic persons by using estimated times to manifest HD based on published algorithms. We followed 19 gene-positive persons who were presymptomatic using an objective criterion (i.e., Quantified Neurological Exam score ≤ 10) at baseline for up to 21 years (median = 5 years) with periannual neuropsychological assessments until a diagnosis of manifest HD. Results showed that our tests of information- and psychomotor-processing speed that place minimal demands on cognition, worsening performance became evident 5-10 years prior to the development of manifest HD. In conclusion, cognitive decline precedes motor signs in HD and may be an important target in clinical trials and early intervention. Cognitive test scores may also improve the ability to predict disease onset among gene mutation carriers and help families to better plan for potential personal and economic hardship.

Mitochondrial modulators in experimental Huntington’s disease: reversal of mitochondrial dysfunctions and cognitive deficits

“…The htt gene located near the telomere of the short arm of chromosome 4 (locus 4p16.3) encodes for huntingtin (Htt) protein (Lin and Beal, 2006). Although, mutation in htt gene was discovered more than 17 years ago, the role of Htt in pathophysiology of HD is still under investigation (Maroof et al, 2011). The most striking neuropathologic hallmark of this disorder is the atrophy of the striatal region, that controls movement, memory, and emotions, suggesting that striatal degeneration is an important aspect of the pathophysiology of HD (Rosas et al, 2002).…”

Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study

“…Changes have been demonstrated in basal ganglia brain volumes (Aylward et al, 2011; Majid et al, 2011) and declines in cognitive performance, primarily emphasizing speeded cognitive processing (Kirkwood et al, 1999; Paulsen et al, 2001, 2013; Lemiere et al, 2002; Maroof et al, 2011), executive function (Snowden et al, 2002; Rupp et al, 2010; O’Rourke et al, 2011; Papp et al, 2013), working memory (Lemiere et al, 2004), visuomotor control (Hart et al, 2011; Tabrizi et al, 2012, 2013), and time production (Rowe et al, 2010). To our knowledge, only one other study has examined multiple phenotypic and biologic markers of change over time together in premanifest HD (Tabrizi et al, 2012, 2013).…”

Movement sequencing in Huntington disease

“…Longitudinal changes in motor functioning over 2–10 years prior to onset include decline in repetitive alternating movements, psychomotor speed, motor timing, saccades and paced and self-paced finger tapping (Penney et al 1990; Giordani et al 1995; Campodonico et al 1996; Kirkwood et al 1999; Lemiere et al 2002, 2004; Witjes-Ane et al 2007; Solomon et al 2008; Antoniades et al 2010; Rowe et al 2010; Maroof et al 2011). …”