TY - JOUR
T1 - Refining the diagnosis of huntington disease
T2 - The PREDICT-HD study
AU - Biglan, Kevin M.
AU - Zhang, Ying
AU - Long, Jeffrey D.
AU - Geschwind, Michael
AU - Kang, Gail A.
AU - Killoran, Annie
AU - Lu, Wenjing
AU - McCusker, Elizabeth
AU - Mills, James A.
AU - Raymond, Lynn A.
AU - Testa, Claudia
AU - Wojcieszek, Joanne
AU - Paulsen, Jane S.
PY - 2013
Y1 - 2013
N2 - Participants with the gene expansion for Huntington disease (HD) but not yet diagnosed were evaluated annually. Unidimensional diagnosis (UD) was a motor diagnosis defined as a diagnostic confidence level (DCL) of 4 (unequivocal motor signs, ≥99% confidence) on the standardized motor exam of the Unified Huntington Disease Rating Scale (UHDRS). Multidimensional diagnosis (MD) was defined as answering yes on Question 80 (Q80) of the UHDRS, ≥99% confidence of manifest HD based on the entire UHDRS. Motor, cognitive, and behavioral measures of phenotype at first diagnosis were compared by t-tests between participants diagnosed via motor exam (UD) and those diagnosed via multidimensional input (MD). Cluster analysis identified clusters based on UHDRS domains.186 participants received a diagnosis of HD during a maximum of 6.4 years of follow-up. In 108 (58.1%) the diagnosis by MD and UD occurred simultaneously, while in 69 (37.1%) the diagnosis by MD occurred prior to UD. Participants who were diagnosed by MD prior to UD were less impaired on motor (12.2 ± 6.7 vs. 22.4 ± 9.3, p < 0.0001), and cognitive (290.7 ± 56.2 vs. 258.0 ± 53.7, p = 0.0002), but not behavioral measures (16.3 ± 21.2 vs. 18.6 ± 22.1, p = 0.49) when compared with those diagnosed simultaneously. Cluster analysis identified three clusters that represented primarily cognitively impaired, behaviorally impaired, and cognitively preserved phenotypes. A multidimensional method results in an earlier diagnosis with less motor and cognitive impairment than a motor diagnosis. Findings have implications for designing preventive trials and providing clinical care in prodromal HD.
AB - Participants with the gene expansion for Huntington disease (HD) but not yet diagnosed were evaluated annually. Unidimensional diagnosis (UD) was a motor diagnosis defined as a diagnostic confidence level (DCL) of 4 (unequivocal motor signs, ≥99% confidence) on the standardized motor exam of the Unified Huntington Disease Rating Scale (UHDRS). Multidimensional diagnosis (MD) was defined as answering yes on Question 80 (Q80) of the UHDRS, ≥99% confidence of manifest HD based on the entire UHDRS. Motor, cognitive, and behavioral measures of phenotype at first diagnosis were compared by t-tests between participants diagnosed via motor exam (UD) and those diagnosed via multidimensional input (MD). Cluster analysis identified clusters based on UHDRS domains.186 participants received a diagnosis of HD during a maximum of 6.4 years of follow-up. In 108 (58.1%) the diagnosis by MD and UD occurred simultaneously, while in 69 (37.1%) the diagnosis by MD occurred prior to UD. Participants who were diagnosed by MD prior to UD were less impaired on motor (12.2 ± 6.7 vs. 22.4 ± 9.3, p < 0.0001), and cognitive (290.7 ± 56.2 vs. 258.0 ± 53.7, p = 0.0002), but not behavioral measures (16.3 ± 21.2 vs. 18.6 ± 22.1, p = 0.49) when compared with those diagnosed simultaneously. Cluster analysis identified three clusters that represented primarily cognitively impaired, behaviorally impaired, and cognitively preserved phenotypes. A multidimensional method results in an earlier diagnosis with less motor and cognitive impairment than a motor diagnosis. Findings have implications for designing preventive trials and providing clinical care in prodromal HD.
KW - Cohort studies
KW - Huntington's disease
KW - Natural history studies
KW - Outcome research
KW - Trinucleotide repeat diseases
UR - http://www.scopus.com/inward/record.url?scp=84876339553&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876339553&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2013.00012
DO - 10.3389/fnagi.2013.00012
M3 - Article
C2 - 23565093
AN - SCOPUS:84876339553
VL - 5
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
IS - APR
M1 - Article 12
ER -