TY - JOUR
T1 - Motor abnormalities in premanifest persons with Huntington's disease
T2 - The PREDICT-HD study
AU - Biglan, Kevin M.
AU - Ross, Christopher A.
AU - Langbehn, Douglas R.
AU - Aylward, Elizabeth H.
AU - Stout, Julie C.
AU - Queller, Sarah
AU - Carlozzi, Noelle E.
AU - Duff, Kevin
AU - Beglinger, Leigh J.
AU - Paulsen, Jane S.
AU - Johnson, Hans
AU - Kieburtz, Karl
AU - Oakes, David
AU - Shoulson, Ira
AU - Guttman, Mark
AU - Hayden, Michael
AU - Landwehrmeyer, Bernhard G.
AU - Nance, Martha
PY - 2009/9/15
Y1 - 2009/9/15
N2 - The PREDICT-HD study seeks to identify clinical and biological markers of Huntington's disease in premanifest individuals who have undergone predictive genetic testing. We compared baseline motor data between geneexpansion carriers (cases) and nongene-expansion carriers (controls) using t-tests and Chi-square. Cases were categorized as near, mid, or far from diagnosis using a CAG-based formula. Striatal volumes were calculated using volumetric magnetic resonance imaging measurements. Multiple linear regression associated total motor score, motor domains, and individual motor items with estimated diagnosis and striatal volumes. Elevated total motor scores at baseline were associated with higher genetic probability of disease diagnosis in the near future (partial R 2 0.14, P < 0.0001) and smaller striatal volumes (partial R 2 0.15, P < 0.0001). Nearly all motor domain scores showed greater abnormality with increasing proximity to diagnosis, although bradykinesia and chorea were most highly associated with diagnostic immediacy. Among individual motor items, worse scores on finger tapping, tandem gait, Luria, saccade initiation, and chorea show unique association with diagnosis probability. Even in this premanifest population, subtle motor abnormalities were associated with a higher probability of disease diagnosis and smaller striatal volumes. Longitudinal assessment will help inform whether motor items will be useful measures in preventive clinical trials.
AB - The PREDICT-HD study seeks to identify clinical and biological markers of Huntington's disease in premanifest individuals who have undergone predictive genetic testing. We compared baseline motor data between geneexpansion carriers (cases) and nongene-expansion carriers (controls) using t-tests and Chi-square. Cases were categorized as near, mid, or far from diagnosis using a CAG-based formula. Striatal volumes were calculated using volumetric magnetic resonance imaging measurements. Multiple linear regression associated total motor score, motor domains, and individual motor items with estimated diagnosis and striatal volumes. Elevated total motor scores at baseline were associated with higher genetic probability of disease diagnosis in the near future (partial R 2 0.14, P < 0.0001) and smaller striatal volumes (partial R 2 0.15, P < 0.0001). Nearly all motor domain scores showed greater abnormality with increasing proximity to diagnosis, although bradykinesia and chorea were most highly associated with diagnostic immediacy. Among individual motor items, worse scores on finger tapping, tandem gait, Luria, saccade initiation, and chorea show unique association with diagnosis probability. Even in this premanifest population, subtle motor abnormalities were associated with a higher probability of disease diagnosis and smaller striatal volumes. Longitudinal assessment will help inform whether motor items will be useful measures in preventive clinical trials.
KW - At-risk
KW - Huntington's disease
KW - UHDRS
UR - http://www.scopus.com/inward/record.url?scp=70449931956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70449931956&partnerID=8YFLogxK
U2 - 10.1002/mds.22601
DO - 10.1002/mds.22601
M3 - Article
C2 - 19562761
AN - SCOPUS:70449931956
SN - 0885-3185
VL - 24
SP - 1763
EP - 1772
JO - Movement Disorders
JF - Movement Disorders
IS - 12
ER -