title: A four-year prospective study of cognitive functioning in Huntington's disease.
abstract: The contribution of neurologic, genetic, and demographic variables to decline in cognition was examined in 70 early- to mid-stage patients with Huntington's disease (HD) using random effects modeling. Study participants were followed prospectively at baseline and at four annual reevaluations. Only modest decline was noted on most neuropsychological variables. Neurologic dysfunction, assessed using the Quantified Neurologic Examination (QNE), proved to be the strongest predictor of cognitive decline. While significantly predictive of more rapid decline in neurologic functioning, CAG repeat length was not generally related to cognitive decline after adjusting for QNE, with the exception of performance on a single test of visual scanning and psychomotor speed (i.e., Trail Making Test, Part A). We propose that CAG repeat length is more closely linked with changes in basal ganglia that predominate in early- to mid-stage HD than with cortical degeneration seen later in disease progression. Such a relationship would explain the predictive value that CAG repeat length plays in changes associated with automatic motor response programs (e.g., QNE and Trail Making Test, Part A) but not in dysfunction on tasks requiring higher-order processing.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. jward24@jhmi.edu
authors.forename: Julianna
authors.initials: J
authors.lastname: Ward
authors.forename: Jeannie-Marie
authors.initials: JM
authors.lastname: Sheppard
authors.forename: Barnett
authors.initials: B
authors.lastname: Shpritz
authors.forename: Russell L
authors.initials: RL
authors.lastname: Margolis
authors.forename: Adam
authors.initials: A
authors.lastname: Rosenblatt
authors.forename: Jason
authors.initials: J
authors.lastname: Brandt
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012720:Severity of Illness Index; D014145:Trail Making Test; D018911:Trinucleotide Repeats / Q000235:genetics