The Trail Making Test (TMT) has long been used to investigate deficits in cognitive processing speed and executive function in humans. However, there are few studies that elucidate the neural substrates of the TMT. The aim of the present study was to identify the brain regional perfusion patterns associated with performance on TMT part B (TMT-B) in patients with amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD). Twenty-one patients with good TMT-B scores and 21 age- and sex-matched patients with poor TMT-B scores were selected. All 42 subjects underwent brain single photon emission computed tomography (SPECT), and the SPECT images were analyzed by statistical parametric mapping. No significant differences between good- and poor-scoring groups were found with respect to years of education, Addenbrooke's Cognitive Examination scores, and scores on TMT-A. Compared to patients with good scores on TMT-B, patients with poor scores showed significant hypoperfusion in the bilateral anterior cingulate extending to the posterior region on the right side, bilateral caudate nucleus and putamen, and bilateral thalamus. Analysis of 63 AD or aMCI subjects revealed significant correlation a between regional cerebral blood flow in the right cingulate cortex and TMT-B scores. Our results suggest that functional activity of the anterior cingulate, striatum and thalamus is closely related to performance time on TMT-B. The performance time on the TMT-B score might be a promising index of dysfunction of the anterior cingulate, striatum, and thalamus among patients with aMCI or mild AD.
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