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Genetics
C09 Age at onset of Huntington's disease: rater estimates versus data based extrapolation
  1. M Orth1,
  2. C Schwenke2,
  3. REGISTRY Investigators
  1. 1Department of Neurology, University of Ulm, Ulm, Germany
  2. 2Scossis, Statistics and Consulting, Berlin, Germany

Abstract

Background The accurate determination of age at onset (AAO) of Huntington's disease is critical to develop and evaluate therapies that aim to delay it.

Aim (1) To compare the raters' estimates of AAO with the estimated AAO calculated with the Langbehn or the Aylward formula. (2) To compare (backwards) extrapolation of actual AAO based on the calculation of disease progression using longitudinal data with the raters' estimates.

Methods 423 REGISTRY participants with at least three visits, demographic information (age, gender), CAG repeat length and Unified Huntington's Disease Rating Scale motor score and total functional capacity (TFC). AAO was calculated based on individual slopes of motor or TFC using generalised linear mixed models. The estimates of the regression were then used to estimate the AAO by calculating the age with motor scores equal or above 5 as well as TFC equal to or below 13 as definitions of manifest disease.

Results Mean AAO (rater estimate) was 44 years; motor onset was present in 303, other onset types in 120. The average motor score at enrolment was 35; 158 (37%) participants were in stage 1, 120 (28%) in stage 2, 111 (26%) in stage 3, 30 (7%) in stage 4 and four (1%) in stage 5. In 357 with positive (motor) or negative (TFC) slopes, the motor score increased linearly by 2.57 points per year. The extrapolated mean AAO of motor signs was 47 (range 13–81, SD 11.67), 3 years after the raters' estimates (agreement rate 0.57 (95% CI 0.51 to 0.62). For the TFC, the raters' estimate was 4 years earlier (agreement rate 0.52 (95% CI 0.47 to 0.57). The best agreement rate was between the extrapolated onset ages on the longitudinal TFC and motor score data (0.76) with TFC onset 4 years after motor onset.

Conclusions The rater estimate of AAO correlated particularly well with the data based calculations of motor, or TFC, AAO. Motor signs precede impairments in day to day life, and both seem a stronger influence on clinicians than age or CAG repeat length.

  • motor signs
  • age at onset
  • TFC

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