Thalamic nicotinic receptors implicated in disturbed consciousness in dementia with Lewy bodies

Abstract

Disturbances of consciousness (DOC) are common in dementia with Lewy bodies (DLB). Following previous findings of preserved temporal cortical high-affinity nicotinic binding relating to DOC, we investigated this receptor in thalamus, an area of high nicotinic receptor concentration, implicated in consciousness. 5-[125I]-A-85380 binding, primarily reflecting the α4β2 subtype, was compared in 16 DLB patients with DOC and 6 without DOC, matched for duration and severity of dementia. Binding was higher in patients with DOC compared to patients without DOC in all thalamic nuclei examined, reaching significance in the reticular and ventral anterior thalamic nuclei. Comparing DLB patients with and without DOC to previously reported controls revealed similar binding levels in patients with DOC and lower binding in patients without DOC, reaching significance in the ventral anterior, indicating preserved nicotinic receptor density in DLB patients with DOC. These findings, together with previous neocortical data, implicate nicotinic modulation of thalamo-cortical circuitry as a key component in the control of conscious awareness in DLB.

Keywords

• Dementia with Lewy bodies
• Consciousness
• Nicotinic receptors
• Thalamus
• 5-I-A-85380