Disturbances of consciousness, including fluctuations in attention and awareness, are a common and clinically important symptom in dementia with Lewy bodies (DLB). In the present study we investigate potential mechanisms of such disturbances of consciousness (DOC) in a clinicopathological study evaluating specific components of the cholinergic system. [3H]Epibatidine binding to the high-affinity nicotinic receptor in the temporal cortex (Brodmann's areas 20 and 36) differentiated DLB cases with and without DOC, being 62-66% higher in those with DOC (F=4.5,p=.025). The were no differences between DLB patients with or without DOC in 125I-labeled alpha-bungaratoxin binding to the low-affinity nicotinic receptor, [3H]pirenzepine binding to the muscarinic M1 receptor, or in choline acetyltransferase activity. These findings provide support for the hypothesis that cholinergic activity is an important neural correlate if consciousness and suggest a mechanism of DOC in DLB involving alterations in the nicotinic receptor, composed of predominantly alpha4 and beta2 subunits.