title: Age, CAG repeat length, and clinical progression in Huntington's disease.
abstract: The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow-up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini-Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%. Graphical models further supported the idea that individuals with smaller triplet expansions experience a more gradual decline. CAG repeat length becomes an important determinant of clinical prognosis when accounting for age of onset. This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. arosenba@jhmi.edu
authors.forename: Adam
authors.initials: A
authors.lastname: Rosenblatt
authors.forename: Brahma V
authors.initials: BV
authors.lastname: Kumar
authors.forename: Alisa
authors.initials: A
authors.lastname: Mo
authors.forename: Claire S
authors.initials: CS
authors.lastname: Welsh
authors.forename: Russell L
authors.initials: RL
authors.lastname: Margolis
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015142:Baltimore; D002648:Child; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult