Are cognitive changes progressive in prediagnostic HD?

To characterize neurocognitive signs of disease progression in prediagnosis and early Huntington disease (HD) and compare the sensitivity of 2 disease staging classification schemes for detecting these signs.

Three hundred and six individuals at-risk for or recently diagnosed with HD completed the Unified Huntington's Disease Rating Scale, genetic testing, and a neurocognitive battery. Two schemes were used to estimate latency to onset of disease. One was based on genetic information (CAG repeat length) and the other was based on the extent of motor signs. Effect sizes were compared to assess the relative sensitivity of the 2 schemes for detecting signs of disease progression.

CAG-expanded participants far from estimated diagnosis performed similarly to controls, whereas those near to estimated diagnosis were impaired relative to controls. Overall, the method employing genetic information yielded larger effect sizes than the motor scheme, particularly for strategic and executive function measures; the motor scheme resulted in a larger effect size for a measure of motor/psychomotor function.

Neurocognitive function is not uniformly affected in prediagnosis and early HD; individuals near to their estimated age of diagnosis have cognitive signs similar to HD, whereas individuals far from estimated diagnosis appear cognitively normal. Classification schemes that incorporate both genetic and phenotypic information may be more sensitive for tracking neurocognitive signs of disease progression.