Abstract
Background
Huntington's disease (HD) is characterized by a progressive multisystem neuronal atrophy
in the brain. Apart from motor signs, cognitive symptoms, particularly executive dysfunctions,
are proposed to be recognizable in early stages of disease. The aim of the present
study was to clarify if cognitive dysfunction in early stages of HD is correlated
with loco-regional structural changes in 3D-MRI.
Methods
Twenty-five patients with genetically confirmed HD in early clinical stages were included
in the study and underwent neuropsychological testing, i.e., the executive tasks Tower
of Hanoi (ToH), Stroop Colour Word Interference Test (STROOP), and modified Wisconsin
Card Sorting Test (mWCST). High-resolution volume-rendering MRI scans (MP-RAGE) were
acquired on a 1.5 T scanner in all patients and were analyzed by statistical parametric
mapping and voxel-based morphometry (VBM) in comparison to an age-matched control
group.
Results
Group analysis of HD patients demonstrated robust regional decreases of gray matter
volumes (p<0.05, corrected for multiple comparisons) in the caudate and the putamen bilaterally
with a global maximum at Talairach coordinates 11/4/11 (Z-score=7.06). Executive dysfunction was significantly correlated with the areas of highest
significant differences out of VBM results which were located bilaterally in the caudate
(ToH: r=0.647, p<0.001; STROOP: r=0.503, p<0.01; mWCST: r=0.452, p<0.05). Moreover, subgroup analyses revealed marked insular atrophy (Talairach coordinates
43/–3/1; Z-score=5.64) in HD patients who performed worse in the single executive tasks.
Conclusion
Two aspects were most remarkable in this correlational study: (i) striatal atrophy
in HD patients in early stages plays an important role not only in impaired motor
control but also in executive dysfunction, and (ii) extrastriatal cortical areas,
i.e., the insular lobe, seem to be involved in executive dysfunction as assessed by
neuropsychological tests requiring for planning and problem solving, stimulus response
selectivity and concept formation.
Keywords
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Article info
Publication history
Accepted:
July 15,
2005
Received in revised form:
June 8,
2005
Received:
March 29,
2005
Identification
Copyright
© 2005 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
