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Abstract Recent studies have demonstrated the usefulness of123 I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy for the diagnosis of dementia with Lewy bodies (DLB). In this study, we investigated the relationship between decreased cardiac MIBG uptake and clinical symptoms in DLB. Thirty-six patients with probable DLB and six normal controls underwent MIBG scintigraphy. We measured the early and delayed heart-to-mediastinum (H/M) ratios, and the results between subgroups based on the presence and absence of clinical symptoms were compared. The mean early and delayed H/M ratios were 1.55 ± 0.29 and 1.42 ± 0.30, and 30 (83.3%) and 33 (91.7%) subjects showed lower values compared to the cutoff, respectively. A statistically significant difference was found only between groups with and without orthostatic hypotension (OH). Among 10 DLB subjects without Parkinsonism, nine patients had a decreased H/M ratio in the delayed image. To our knowledge, this is the first study to correlate decreased MIBG uptake with the clinical symptoms of DLB, and to show a significantly lower H/M ratio in subjects with OH. Furthermore, we found that MIBG scintigraphy could detect cardiac sympathetic denervation regardless of clinically evident Parkinsonism. These results suggest that MIBG myocardial scintigraphy could be a valuable diagnostic test in the clinical diagnosis of DLB.