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Decreased frontal choline and neuropsychological performance in preclinical Huntington disease

From the Radiology Department, Diagnostic Imaging Center (CDI) (B.G.-A.), and Neurology Service, Institut Clínic de Neurociències (ICN) (E.M., E.T.), Hospital Clinic; IDIBAPS (B.G.-A., E.M., E.T.); Fundació ACE (M.A.), Institut Català de Neurociències Aplicades; Fundació Hospital Clínic (A.S., G.C.M.); and University of Barcelona (E.M., E.T.), Barcelona, Spain.

Address correspondence and reprint requests to Dr. Beatriz Gomez-Anson, Consultant Neuroradiologist, Radiology Department, CDI, Hospital Clinic, C/Villaroel 170, Barcelona 08023, Spain; e-mail: banson{at}clinic.ub.es

Objectives: To study metabolic brain changes in preclinical carriers of Huntington disease (PreHD) using proton magnetic resonance spectroscopy (¹H-MRS) and to examine their relationship to neuropsychological performance.

Methods: Seventeen subjects with PreHD and 17 controls, matched for age and education, were studied. Frontal cortex and basal ganglia ¹H-MRS, and a detailed neuropsychological battery, including visuomotor integration and speed, and memory, frontal, and visuospatial tests were performed. Statistical analysis included Student t-test and Pearson correlations (significance p < 0.05).

Results: Frontal choline-containing compounds (CHO) were decreased in PreHD [t (32) = –2.834, p = 0.008]. Subjects with PreHD performed worse than controls in the 15-Objects test [t (32) = 4.077, p = 0.000], Luria motor alternances [t (32) = –2.094, p = 0.044], and Symbol Digit tests [t (32) = –2.136, p = 0.040]. Decreased frontal CHO in PreHD correlated to slowing in visuomotor tasks (the 15-Objects test: r = –0.60, p = 0.000, and the Symbol Digit: r = 0.37, p = 0.047).

Conclusion: As choline-containing compounds relate to membrane turnover, membrane dysfunction antedating neuronal death is suggested to occur in the frontal cortex in preclinical carriers of Huntington disease. This dysfunction may be responsible for some of the neuropsychological deficits observed.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 20 issue to find the title link for this article.

Supported by the Spanish Ministry of Health (FISS 02/0451) and Red CIEN IDIBAPS-ISCIII RTIC C03/06.

Disclosure: Uriach Co. paid A. Sainz. The other authors report no conflicts of interest.

Received May 16, 2006. Accepted in final form November 20, 2006.

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