Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-23T09:59:13.989Z Has data issue: false hasContentIssue false
  • English
  • Français

A four-year prospective study of cognitive functioning in Huntington's disease

Published online by Cambridge University Press:  14 July 2006

JULIANNA WARD ,
JEANNIE-MARIE SHEPPARD ,
BARNETT SHPRITZ ,
RUSSELL L. MARGOLIS ,
ADAM ROSENBLATT  and
JASON BRANDT
JULIANNA WARD
Affiliation:
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
JEANNIE-MARIE SHEPPARD
Affiliation:
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
BARNETT SHPRITZ
Affiliation:
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
RUSSELL L. MARGOLIS
Affiliation:
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
ADAM ROSENBLATT
Affiliation:
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
JASON BRANDT
Affiliation:
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland
Get access Rights & Permissions [Opens in a new window]

Abstract

The contribution of neurologic, genetic, and demographic variables to decline in cognition was examined in 70 early- to mid-stage patients with Huntington's disease (HD) using random effects modeling. Study participants were followed prospectively at baseline and at four annual reevaluations. Only modest decline was noted on most neuropsychological variables. Neurologic dysfunction, assessed using the Quantified Neurologic Examination (QNE), proved to be the strongest predictor of cognitive decline. While significantly predictive of more rapid decline in neurologic functioning, CAG repeat length was not generally related to cognitive decline after adjusting for QNE, with the exception of performance on a single test of visual scanning and psychomotor speed (i.e., Trail Making Test, Part A). We propose that CAG repeat length is more closely linked with changes in basal ganglia that predominate in early- to mid-stage HD than with cortical degeneration seen later in disease progression. Such a relationship would explain the predictive value that CAG repeat length plays in changes associated with automatic motor response programs (e.g., QNE and Trail Making Test, Part A) but not in dysfunction on tasks requiring higher-order processing. (JINS, 2006, 12, 445–454.)

Keywords

Huntington's diseaseLongitudinalProspectiveNeurologic dysfunctionBasal gangliaTrinucleotide repeats
Type
Research Article
Information
Journal of the International Neuropsychological Society , Volume 12 , Issue 4 , July 2006 , pp. 445 - 454
Copyright
© 2006 The International Neuropsychological Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bamford, K.A., Caine, E.D., Kido, D.K., Cox, C., & Shoulson, I. (1995). A prospective evaluation of cognitive decline in early Huntington's disease: Functional and radiographic correlates. Neurology, 45, 1867–1873.
Bauchoud-Levi, A.C., Maison, P., Bartolomeo, P., Boisse, M.F., Barba, G.D., Ergis, A.M., Baudic, S., Degos, J.D., Cesaro, P., & Peschanski, M. (2001). Retest effects and cognitive decline in longitudinal follow-up of patients with early HD. Neurology, 56, 1052–1058.
Brandt, J. (1991). Cognitive impairments in Huntington's disease: Insights into the neuropsychology of the striatum. In F. Boller & J. Grafman (eds.), Handbook of neuropsychology (pp. 241–264). Amsterdam: Elsevier.
Brandt, J., Bylsma, F.W., Gross, R., Stine, O.C., Ranen, N., & Ross, C.A. (1996). Trinucleotide repeat length and clinical progression in Huntington's disease. Neurology, 46, 527–531.
Brandt, J., Strauss, M.E., Larus, J., Jensen, B., Folstein, S.E., & Folstein, M.F. (1984). Clinical correlates of dementia and disability in Huntington's disease. Journal of Clinical Neuropsychology, 6, 401–412.
Brinkman, R.R., Mezei, M.M., Theilmann, J., Almqvist, E., & Hayden, M.R. (1997). The likelihood of being affected with Huntington's disease by a particular age, for a specific CAG size. American Journal of Human Genetics, 60, 1202–1210.
Butters, N., Sax, D., Montgomery, K., & Tarlow, S. (1978). Comparison of the neuropsychological deficits associated with early and advanced Huntington's disease. Archives of Neurology, 35, 585–589.
Bylsma, F.W., Rothlind, J., Hall, M.R., Folstein, S.E., & Brandt, J. (1993). Assessment of adaptive function in Huntington's disease. Movement Disorders, 8, 183–190.
Folstein, S.E. (1989). Huntington's disease: A disorder of families. Baltimore, MD: Johns Hopkins University Press.
Folstein, S.E., Jensen, B., Leigh, R.J., & Folstein, M.F. (1983). The measurement of abnormal movement: Methods developed for Huntington's disease. Neurobehavioral Toxicology and Teratology, 5, 605–609.
Foroud, T., Siemers, E., Kleindorfer, D., Bill, D.J., Hodes, M.E., Norton, J.A., Conneally, P.M., & Christian, J.C. (1995). Cognitive scores in carriers of Huntington's disease gene compared to noncarriers. Annals of Neurology, 37, 657–664.
Gomez-Tortosa, E., Barrio, A.D., Ruiz, P.J.G., Pernaute, R.S., Benitez, J., Barroso, A., Jimenez, J., & Yebenes, J.G. (1998). Severity of cognitive impairment in juvenile and late-onset Huntington's disease. Archives of Neurology, 55, 835–843.
Huntington's Disease Collaborative Research Group (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 72, 971–983.
Hahn-Barma, V., Deweer, B., Durr, A., Dode, C., Feingold, J., Pillon, B., Agid, Y., Brice, A., & Dubois, B. (1998). Are cognitive changes the first symptoms of Huntington's disease? A study of gene carriers. Journal of Neurology, Neurosurgery, and Psychiatry, 64, 172–177.
Ho, A.K., Sahakian, B.J., Brown, R.G., Barker, R.A., Hodges, J.R., Ane, M.N., Snowden, J., Thompson, J., Esmonde, T., Gentry, R., Moore, J.W., & Bodner, T. (2003). Profile of cognitive progression in early Huntington's disease. Neurology, 61, 1702–1706.
Joel, D. (2001). Open interconnected model of basal ganglia-thalamocortical circuitry and its relevance to the clinical syndrome of Huntington's disease. Movement Disorders, 16, 407–423.
Kirkwood, S.C., Su, J.L., Conneally, P.M., & Foroud, T. (2001). Progression of symptoms in early and middle stages of Huntington disease. Archives of Neurology, 58, 273–278.
Lawrence, A.D., Sahakian, B.J., Hodges, J.R., Rosser, A.E., Lange, K.W., & Robbins, T.W. (1996). Executive and mnemonic functions in early Huntington's disease. Brain, 119, 1633–1645.
Mahant, N., McCusker, E.A., Byth, K., & Graham, S. (2003). Huntington's disease: Clinical correlates of disability and progression. Neurology, 61, 1085–1092.
Middleton, F.A. & Strick, P.L. (2002). Basal-ganglia projections to the prefrontal cortex of the primate. Cerebral Cortex, 12, 926–935.
Mohr, E., Brouwers, P., Claus, J.J., Mann, U.M., Fedio, P., & Chase, T.N. (1991). Visuospatial cognition in Huntington's disease. Movement Disorders, 6, 127–132.
Nehl, C. & Paulsen, J.S. (2004). Cognitive and psychiatric aspects of Huntington's disease coontribute to functional capacity. Journal of Nervous and Mental Disease, 192, 72–74.
Rosenblatt, A., Liang, K.Y., Zhou, H., Abbott, M.H., Gourley, L.M., Margolis, R.L., Brandt, J., & Ross, C.A. (2006). The association of CAG repeat length with clinical progression in Huntington's disease. Neurology, 66, 1016–1020.
Rothlind, J.C., Bylsma, F.W., Peyser, C., Folstein, S.E., & Brandt, J. (1993). Cognitive and motor corelates of everyday functioning in early Huntington's disease. Journal of Nervous and Mental Disease, 181, 194–199.
Snowden, J., Craufurd, D., Griffiths, H., Thompson, J., & Neary, D. (2001). Longitudinal evaluation of cognitive disorder in Huntington's disease. Journal of the International Neuropsychological Society, 7, 33–44.
Stine, O.C., Pleasant, N., Franz, M.L., Abbott, M.H., Folstein, S.E., & Ross, C.A. (1993). Correlation between onset age of Huntington's disease and the length of the trinucleotide repeat in IT-15. Human Molecular Genetics, 2, 1247–1249.
Wechsler, D. (1981). Wechsler Adult Intelligence Scale-Revised (WAIS-R) Manual. New York, NY: The Psychological Corporation.
Witjes-Ane, M.N.W., van der Vlis, M.V., van Vugt, J.P.P., Lanser, J.B.K., Hermans, J., Zwindermann, A.H., Ommen, G.J.B. v., & Roos, R.A.C. (2003). Cognitive and motor functioning in gene carriers for Huntington's disease: A baseline study. Journal of Neuropsychiatry and Clinical Neurosciences, 15, 7–16.