Introduction: To investigate in vivo differences in the distribution of alpha 4 beta 2 subtypes of nAChR using the ligand I-123-5-Iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) and single photon emission computed tomography (SPECT) in DLB and similarly aged controls. Methods: Thirty-one subjects (15 DLB and 16 controls) underwent I-123-5IA-85380 and perfusion (Tc-99m-exametazime) SPECT scanning. Patient scans were compared to scans of control subjects on a voxel-by-voxel basis using SPM2. Results: Compared to controls, significant reductions in relative I-123-5IA-85380 uptake were identified in frontal, striatal, temporal and cingulate regions in DLB. Elevation of scaled I-123-5IA-85380 uptake in occipital cortex was observed in DLB relative to controls, as well as being associated with DLB subjects with a recent history of visual hallucinations. Changes in I-123-5IA-85380 SPECT in DLB were different from perfusion. Conclusion: Reductions in normalised I-123-5IA-85380 uptake in DLB were distinct from their perfusion deficits. Significant increase in occipital lobe uptake was present in DLB, a change most pronounced in subjects with a recent history of visual hallucinations. The findings directly link cholinergic changes in occipital lobe to visual hallucinations in DLB. (C) 2008 Elsevier Inc. All rights reserved.