We evaluated the diagnostic usefulness of combination studies with a statistical mapping method in N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) brain perfusion SPECT, cardiac sympathetic nerve function by (123)I-metaiodobenzylguanidine ((123)I-MIBG), and myocardial function by electrocardiographically gated (99m)Tc-sestamibi ((99m)Tc-MIBI) SPECT for patients with probable or possible dementia with Lewy bodies (DLB). METHODS Twelve patients with probable DLB (7 male, 5 female; mean age +/- SD, 72.3 +/- 5.63 y; range, 65-82 y) and 9 patients with possible DLB (3 male, 6 female; mean age +/- SD, 73.1 +/- 9.23 y; range, 59-88 y) were enrolled in this study. (123)I-IMP SPECT images were analyzed with 3-dimensional stereotactic surface projections (3D-SSP) and the severity of ischemia was classified objectively using quantitatively analytic and display software; stereotactic extraction estimation (SEE) methods were compared with a normal database. In addition, we evaluated (123)I-MIBG heart-to-mediastinum (H/M) uptake ratios. Moreover, we performed (99m)Tc-MIBI SPECT to evaluate myocardial perfusion and the left ventricular ejection fraction (LVEF) compared with a normal database. RESULTS 3D-SSP images of group comparison with healthy control subjects showed significantly decreased perfusion in the parietotemporal, occipital cortex, posterior cingulated, and precuneus regions in the probable DLB group but no significant reduction in the possible DLB group. Mean H/M ratios in the probable DLB group were significantly lower than those of the possible DLB group and the control group, respectively. Ten of 12 patients (83.3%) with probable DLB and 1 of 9 patients (11.1%) with possible DLB showed severe reduction in the bilateral occipital lobe and also a low (123)I-MIBG uptake. One patient (8.3%) with probable DLB and 2 patients (22.2%) with possible DLB showed no bilateral occipital hypoperfusion but showed low (123)I-MIBG uptake. One patient (8.3%) with probable DLB and 6 patients (66.7%) with possible DLB showed no occipital hypoperfusion and normal (123)I-MIBG uptake. (99m)Tc-MIBI gated SPECT did not indicate any wall motion abnormality in any subjects. CONCLUSIONS These results suggest that combined examination of cerebral blood flow with 3D-SSP and SEE analysis, and cardiac sympathetic nerve function with (123)I-MIBG, would be a useful supporting diagnostic method in patients with DLB-particularly, in possible DLB and when cerebral blood flow does not indicate occipital hypoperfusion.