Cognitive domains that predict time to diagnosis in prodromal Huntington disease

Deborah Lynn Harrington, Megan M. Smith, Ying Zhang, Noelle E. Carlozzi, Jane S. Paulsen, Eric A. Epping, Hans Johnson, Janet Williams, Leigh Beglinger, Jeffrey D. Long, James A. Mills, Elizabeth Aylward, Kevin Biglan, Blair Leavitt, Marcy MacDonald, Martha Nance, Joanne Wojcieszek

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Prodromal Huntington's disease (prHD) is associated with a myriad of cognitive changes but the domains that best predict time to clinical diagnosis have not been studied. This is a notable gap because some domains may be more sensitive to cognitive decline, which would inform clinical trials. Objectives: The present study sought to characterise cognitive domains underlying a large test battery and for the first time, evaluate their ability to predict time to diagnosis. Methods: Participants included gene negative and gene positive prHD participants who were enrolled in the PREDICT-HD study. The CAG - age product (CAP) score was the measure of an individual's genetic signature. A factor analysis of 18 tests was performed to identify sets of measures or latent factors that elucidated core constructs of tests. Factor scores were then fit to a survival model to evaluate their ability to predict time to diagnosis. Results: Six factors were identified: (1) speed/inhibition, (2) verbal working memory, (3) motor planning/speed, (4) attention - information integration, (5) sensory - perceptual processing and (6) verbal learning/memory. Factor scores were sensitive to worsening of cognitive functioning in prHD, typically more so than performances on individual tests comprising the factors. Only the motor planning/speed and sensory - perceptual processing factors predicted time to diagnosis, after controlling for CAP scores and motor symptoms. Conclusions: The results suggest that motor planning/speed and sensory - perceptual processing are important markers of disease prognosis. The findings also have implications for using composite indices of cognition in preventive Huntington's disease trials where they may be more sensitive than individual tests.

Original languageEnglish (US)
Pages (from-to)612-619
Number of pages8
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume83
Issue number6
DOIs
StatePublished - Jan 1 2012

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Huntington Disease
Aptitude
Verbal Learning
Short-Term Memory
Cognition
Genes
Statistical Factor Analysis
Clinical Trials

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Cognitive domains that predict time to diagnosis in prodromal Huntington disease. / Harrington, Deborah Lynn; Smith, Megan M.; Zhang, Ying; Carlozzi, Noelle E.; Paulsen, Jane S.; Epping, Eric A.; Johnson, Hans; Williams, Janet; Beglinger, Leigh; Long, Jeffrey D.; Mills, James A.; Aylward, Elizabeth; Biglan, Kevin; Leavitt, Blair; MacDonald, Marcy; Nance, Martha; Wojcieszek, Joanne.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 83, No. 6, 01.01.2012, p. 612-619.

Research output: Contribution to journalArticle

Harrington, DL, Smith, MM, Zhang, Y, Carlozzi, NE, Paulsen, JS, Epping, EA, Johnson, H, Williams, J, Beglinger, L, Long, JD, Mills, JA, Aylward, E, Biglan, K, Leavitt, B, MacDonald, M, Nance, M & Wojcieszek, J 2012, 'Cognitive domains that predict time to diagnosis in prodromal Huntington disease', Journal of Neurology, Neurosurgery and Psychiatry, vol. 83, no. 6, pp. 612-619. https://doi.org/10.1136/jnnp-2011-301732
Harrington, Deborah Lynn ; Smith, Megan M. ; Zhang, Ying ; Carlozzi, Noelle E. ; Paulsen, Jane S. ; Epping, Eric A. ; Johnson, Hans ; Williams, Janet ; Beglinger, Leigh ; Long, Jeffrey D. ; Mills, James A. ; Aylward, Elizabeth ; Biglan, Kevin ; Leavitt, Blair ; MacDonald, Marcy ; Nance, Martha ; Wojcieszek, Joanne. / Cognitive domains that predict time to diagnosis in prodromal Huntington disease. In: Journal of Neurology, Neurosurgery and Psychiatry. 2012 ; Vol. 83, No. 6. pp. 612-619.
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AU - Epping, Eric A.

AU - Johnson, Hans

AU - Williams, Janet

AU - Beglinger, Leigh

AU - Long, Jeffrey D.

AU - Mills, James A.

AU - Aylward, Elizabeth

AU - Biglan, Kevin

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