Decreased frontal choline and neuropsychological performance in preclinical Huntington disease

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.