Clinical markers of early disease in persons near onset of Huntington's disease

Objective: There is increasing evidence that neuron loss precedes the pheno typic expression of Huntington's disease (HD). As genes for late-onset neur odegenerative diseases are identified, the need for accurate assessment of phenoconversion (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 Huntingt on 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 year s later, showed that 70 persons were given a diagnosis of definite HD based on the quantified neurologic examination. Results: Baseline cognitive perf ormances were consistently worse for the at-risk group who demonstrated con version to a definitive diagnosis compared with those who did not. Longitud inal change scores showed that the at-risk group who did not demonstrate ma nifest disease during the follow-up study period demonstrated improvements in all cognitive tests, whereas performances in the at-risk group demonstra ting conversion to disease during the study declined across cognitive domai ns. Conclusions: Neuropsychological measures show impairment 2 years before the development of more manifest motor disease. Findings suggest that thes e brief cognitive measures administered over time may capture early striata l neural loss in HD.