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Selective neuronal damage and Wisconsin Card Sorting Test performance in atherosclerotic occlusive disease of the major cerebral artery
  1. Hiroshi Yamauchi1,
  2. Ryuichi Nishii2,
  3. Tatsuya Higashi2,
  4. Shinya Kagawa2,
  5. Hidenao Fukuyama1
  1. 1Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
  2. 2Research Institute, Shiga Medical Center, Moriyama, Japan
  1. Correspondence to Dr Hiroshi Yamauchi, Human Brain Research Center, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; yamauchi{at}


Background In atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA) disease, selective neuronal damage can be detected as a decrease in central benzodiazepine receptors (BZRs) in the normal-appearing cerebral cortex. This study aimed to determine whether a decrease in the BZRs in the non-infarcted cerebral cortex is associated with poor performance on the Wisconsin Card Sorting Test (WCST), which assesses executive functions.

Methods The authors measured the BZRs using positron emission tomography and 11C-flumazenil in 60 non-disabled patients with unilateral atherosclerotic ICA or MCA disease and no cortical infarction. Using three-dimensional stereotactic surface projections, the abnormally decreased BZR index (extent (%) of pixels with Z score >2 compared with controls×average Z score in those pixels) in the cerebral cortex of the anterior cerebral artery (ACA) or MCA territory was calculated and found to be correlated with the patient's score on the WCST.

Results On the basis of the WCST results, 39 patients were considered abnormal (low categories achieved) for their age. The BZR index of the ACA territory in the hemisphere affected by arterial disease was significantly higher in abnormal patients than in normal patients. The BZR index of the MCA territory differed significantly between the two groups when patients with left arterial disease (n=28) were analysed separately.

Conclusions In atherosclerotic ICA or MCA disease, selective neuronal damage that is manifested as a decrease in BZRs in the non-infarcted cerebral cortex may contribute to the development of executive dysfunction.

  • Carotid artery disease
  • middle cerebral artery disease
  • positron emission tomography
  • Wisconsin Card Sorting test
  • benzodiazepine receptor
  • cerebrovascular disease
  • cognition
  • pet
  • ligand studies
  • stroke

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  • Funding This study was supported in part by a Grant-in-Aid for Scientic Research from Japan Society for the Promotion of Science (22613001).

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the Ethics Committee of Shiga Medical Centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.