Clinical markers of early disease in persons near onset of Huntington's
Clinical markers of early disease in persons
near onset of Huntington's disease
Objective:- There is increasing evidence that
neuron loss precedes the phenotypic expression of Huntington's disease (HD). As genes for late-onset neurodegenerative diseases
are identified, the need for accurate assessment of pheno-conversion (i.e., the transition from health to the disease
phenotype) will be important.
Methods:- Prospective longitudinal evaluation using the Unified Huntington's
Disease Rating Scale (UHDRS) was conducted by Huntington Study Group members from 36 sites.
There were 260 persons considered "at risk" for HD who initially did not have manifest
disease and had at least one subsequent evaluation.
Repeat UHDRS data, obtained an average of 2 years later, showed that 70 persons
were given a
diagnosis of definite HD based on the quantified neurologic examination.
Results:- Baseline cognitive performances
were consistently worse for the at-risk group who demonstrated conversion to a definitive diagnosis compared with those who
did not. Longitudinal change scores showed that the at-risk group who did not demonstrate manifest disease during
the follow-up study period demonstrated improvements in all cognitive tests, whereas performances in the at-risk group
conversion to disease during the study declined across cognitive domains.
Neuropsychological measures show impairment 2 years before
the development of more manifest motor disease. Findings suggest that these brief cognitive measures administered over time
may capture early striatal neural loss in HD.
J. S. Paulsen, PhD;, H. Zhao, ScD;, J. C. Stout, PhD;, R. R. Brinkman, BSc;, M. Guttman, MD;, C. A. Ross,
PhD, MD;, P. Como, PhD;, C. Manning, PhD;, M. R. Hayden, PhD, MD;, I. Shoulson, MD and the Huntington Study Group*
the University of Iowa (Dr. Paulsen), Iowa City; University of Rochester (Drs. Como, Shoulsen, and Zhao), NY; Indiana University
(Dr. Stout), Bloomington;
University of British Columbia (Dr. Hayden and R. Brinkman), Vancouver, BC, Canada; University
of Toronto (Dr. Guttman), Ontario, Canada; Johns Hopkins University (Dr. Ross), Baltimore, MD; and the University of
Virginia (Dr. Manning), Charlottesville.