Prefrontal cortex volume reduction on MRI in preclinical Huntington's disease relates to visuomotor performance and CAG number.
OBJECTIVE
To investigate grey matter volumes on magnetic resonance imaging (MRI) in preclinical Huntington's disease (HD), and their relationship to neuropsychology and CAG number.


METHODS
Twenty preclinical HD carriers and 21 healthy controls matched for age, sex, and educational level were included in this study. Clinical (UHDRS), and detailed neuropsychological assessments, and 3D IR SPGR axial MR acquisition. Calculation of global, segmented (SIENAX), and focal (voxel based morphometry, VBM) grey matter volumes was carried out. An analysis of variance (ANOVA) and a general linear model for VBM analysis were used to compare preclinical HD carriers and controls. Small volume correction was used, and clusters at p<0.05 were considered significant. Correlation analysis (VBM) with neuropsychology, and CAG number was also performed.


RESULTS
Preclinical HD carriers showed, compared to controls, smaller global volumes of the brain (1279+/-6 vs. 1331+/-46, p=0.003), total (666+/-48 vs. 698+/-34, p=0.020) and cortical grey matter (551+/-44 vs. 577+/-32, p=0.035). When compared to the controls, preclinical carriers showed focal volume losses, which were more prominent in the left prefrontal cortex, cerebellum, and right posterior temporal cortex. Preclinical HD performed slower in a visuomotor integration task, the 15-Objects test, than controls (t (1,25.02)=3.69; p=0.001: pre-HD: 69.55+/-28.86; controls: 45.79+/-8.38). A correlation was found between volume loss in the prefrontal cortex, visuomotor performance, and CAG number.


CONCLUSIONS
Preclinical HD carriers show grey matter volume reduction involving the prefrontal cortex, which relates to the visuomotor performance and CAG number. This suggests that regionally selective neuronal loss/dysfunction occurs prior to the clinical onset of symptoms.
Gómez-Ansón
B
B
Department of Radiology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. bgomeza@santpau.es
Alegret
M
M
Muñoz
E
E
Monté
G C
GC
Alayrach
E
E
Sánchez
A
A
Boada
M
M
Tolosa
E
E
D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D007839:Functional Laterality; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000473:pathology*; D012720:Severity of Illness Index; D018911:Trinucleotide Repeats / Q000235:genetics*; D014796:Visual Perception / Q000235:genetics / Q000502:physiology*; D055815:Young Adult