TY - JOUR
T1 - Multivariate prediction of motor diagnosis in Huntington's disease
T2 - 12 years of PREDICT-HD
AU - PREDICT-HD Investigators and Coordinators of the Huntington Study Group
AU - Long, Jeffrey D.
AU - Paulsen, Jane S.
AU - Soriano, Isabella De
AU - Shadrick, Courtney
AU - Miller, Amanda
AU - Chiu, Edmond
AU - Preston, Joy
AU - Goh, Anita
AU - Antonopoulos, Stephanie
AU - Loi, Samantha
AU - Chua, Phyllis
AU - Komiti, Angela
AU - Raymond, Lynn
AU - Decolongon, Joji
AU - Fan, Mannie
AU - Coleman, Allison
AU - Ross, Christopher A.
AU - Varvaris, Mark
AU - Ong, Maryjane
AU - Yoritomo, Nadine
AU - Mallonee, William M.
AU - Suter, Greg
AU - Samii, Ali
AU - Freney, Emily P.
AU - Macaraeg, Alma
AU - Jones, Randi
AU - Wood-Siverio, Cathy
AU - Factor, Stewart A.
AU - Barker, Roger A.
AU - Mason, Sarah
AU - Guzman, Natalie Valle
AU - McCusker, Elizabeth
AU - Griffith, Jane
AU - Loy, Clement
AU - McMillan, Jillian
AU - Gunn, David
AU - Orth, Michael
AU - Submuth, Sigurd
AU - Barth, Katrin
AU - Trautmann, Sonja
AU - Schwenk, Daniela
AU - Eschenbach, Carolin
AU - Quaid, Kimberly
AU - Wesson, Melissa
AU - Wojcieszek, Joanne
AU - Guttman, Mark
AU - Sheinberg, Alanna
AU - Law, Albie
AU - Perlmutter, Joel
AU - Mazzoni, Pietro
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/10
Y1 - 2015/10
N2 - Background: It is well known in Huntington's disease that cytosine-adenine-guanine expansion and age at study entry are predictive of the timing of motor diagnosis. The goal of this study was to assess whether additional motor, imaging, cognitive, functional, psychiatric, and demographic variables measured at study entry increased the ability to predict the risk of motor diagnosis over 12 years. Methods: One thousand seventy-eight Huntington's disease gene-expanded carriers (64% female) from the Neurobiological Predictors of Huntington's Disease study were followed up for up to 12 y (mean=5, standard deviation=3.3) covering 2002 to 2014. No one had a motor diagnosis at study entry, but 225 (21%) carriers prospectively received a motor diagnosis. Analysis was performed with random survival forests, which is a machine learning method for right-censored data. Results: Adding 34 variables along with cytosine-adenine-guanine and age substantially increased predictive accuracy relative to cytosine-adenine-guanine and age alone. Adding six of the common motor and cognitive variables (total motor score, diagnostic confidence level, Symbol Digit Modalities Test, three Stroop tests) resulted in lower predictive accuracy than the full set, but still had twice the 5-y predictive accuracy than when using cytosine-adenine-guanine and age alone. Additional analysis suggested interactions and nonlinear effects that were characterized in a post hoc Cox regression model. Conclusions: Measurement of clinical variables can substantially increase the accuracy of predicting motor diagnosis over and above cytosine-adenine-guanine and age (and their interaction). Estimated probabilities can be used to characterize progression level and aid in future studies' sample selection.
AB - Background: It is well known in Huntington's disease that cytosine-adenine-guanine expansion and age at study entry are predictive of the timing of motor diagnosis. The goal of this study was to assess whether additional motor, imaging, cognitive, functional, psychiatric, and demographic variables measured at study entry increased the ability to predict the risk of motor diagnosis over 12 years. Methods: One thousand seventy-eight Huntington's disease gene-expanded carriers (64% female) from the Neurobiological Predictors of Huntington's Disease study were followed up for up to 12 y (mean=5, standard deviation=3.3) covering 2002 to 2014. No one had a motor diagnosis at study entry, but 225 (21%) carriers prospectively received a motor diagnosis. Analysis was performed with random survival forests, which is a machine learning method for right-censored data. Results: Adding 34 variables along with cytosine-adenine-guanine and age substantially increased predictive accuracy relative to cytosine-adenine-guanine and age alone. Adding six of the common motor and cognitive variables (total motor score, diagnostic confidence level, Symbol Digit Modalities Test, three Stroop tests) resulted in lower predictive accuracy than the full set, but still had twice the 5-y predictive accuracy than when using cytosine-adenine-guanine and age alone. Additional analysis suggested interactions and nonlinear effects that were characterized in a post hoc Cox regression model. Conclusions: Measurement of clinical variables can substantially increase the accuracy of predicting motor diagnosis over and above cytosine-adenine-guanine and age (and their interaction). Estimated probabilities can be used to characterize progression level and aid in future studies' sample selection.
KW - Assessment of cognitive disorders/dementia
KW - Clinical trials methodology/study design
KW - Huntington's disease
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=84944452142&partnerID=8YFLogxK
U2 - 10.1002/mds.26364
DO - 10.1002/mds.26364
M3 - Article
C2 - 26340420
AN - SCOPUS:84944452142
SN - 0885-3185
VL - 30
SP - 1664
EP - 1672
JO - Movement Disorders
JF - Movement Disorders
IS - 12
ER -