P2-147 123I-QNB spect demonstrates loss of cholinergic muscarinic receptors in Alzheimer's disease, but occipital increases in dementia with Lewy bodies and Parkinson's disease dementia

Abstract

Background: Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Dementia in Parkinson's disease (PDD) are all associated with loss of ascending cholinergic pathways, though autopsy studies suggest differential patterns of cholinergic receptor loss. Objective(s): To investigate whether differences between dementia subtypes in cholinergic muscarinic receptors could be demonstrated in vivo using SPECT imaging Methods: 81 subjects (18 AD, 14 DLB, 25 PDD and 24 normal older controls) underwent Single Photon Emission Computed Tomography imaging after injection of (R,R)123I-QNB, a ligand showing high specificity for the postsynaptic muscarinic m l receptor. Changes in uptake relative to controls were analysed using statistical parametric mapping (SPM99). Results: AD subjects showed reduced 123I-QNB uptake in inferior frontal, temporal and occipito-temporal areas (Pcorrected<0.001). Similar changes were seen in PDD (Pcorrected<0.001) but not DLB subjects. DLB and PDD (but not AD) subjects showed evidence of increased QNB binding in occipital lobe. Conclusions: Muscarinic receptor changes in vivo, as detected using QNB-SPECT differed between groups. In contrast to a loss of receptors in AD, DLB was associated with relative preservation and an increase in occipital lobes, a change also seen in PDD. This may reflect occipital receptor upregulation in DLB and PDD in response to cholinergic deficit and may relate to key clinical features such hallucinations and visuospatial impairments.