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The potential of composite cognitive scores for tracking progression in Huntington's disease.

BACKGROUND
Composite scores derived from joint statistical modelling of individual risk factors are widely used to identify individuals who are at increased risk of developing disease or of faster disease progression.


OBJECTIVE
We investigated the ability of composite measures developed using statistical models to differentiate progressive cognitive deterioration in Huntington's disease (HD) from natural decline in healthy controls.


METHODS
Using longitudinal data from TRACK-HD, the optimal combinations of quantitative cognitive measures to differentiate premanifest and early stage HD individuals respectively from controls was determined using logistic regression. Composite scores were calculated from the parameters of each statistical model. Linear regression models were used to calculate effect sizes (ES) quantifying the difference in longitudinal change over 24 months between premanifest and early stage HD groups respectively and controls. ES for the composites were compared with ES for individual cognitive outcomes and other measures used in HD research. The 0.632 bootstrap was used to eliminate biases which result from developing and testing models in the same sample.


RESULTS
In early HD, the composite score from the HD change prediction model produced an ES for difference in rate of 24-month change relative to controls of 1.14 (95% CI: 0.90 to 1.39), larger than the ES for any individual cognitive outcome and UHDRS Total Motor Score and Total Functional Capacity. In addition, this composite gave a statistically significant difference in rate of change in premanifest HD compared to controls over 24-months (ES: 0.24; 95% CI: 0.04 to 0.44), even though none of the individual cognitive outcomes produced statistically significant ES over this period.


CONCLUSIONS
Composite scores developed using appropriate statistical modelling techniques have the potential to materially reduce required sample sizes for randomised controlled trials.