In vivo SPECT imaging of muscarinic acetylcholine receptors using ( R, R) 123I-QNB in dementia with Lewy bodies and Parkinson’s disease dementia

Alterations in cholinergic function have been reported to be associated with dementia. The aim of this study was to investigate differences in the distribution of muscarinic acetylcholine receptors (mAChRs) using ( R, R) 123I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD) and age-matched controls. 123I-QNB binding was also compared to the corresponding cerebral perfusion changes in the same subjects. 63 subjects (24 controls, 14 DLB, 25 PDD) underwent 123I-QNB and perfusion 99mTc-exametazine SPECT scanning. Image analysis, using statistical parametric mapping (SPM99), involved spatial normalisation of each image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean whole brain uptake. Group effects and correlations were assessed using two sample t tests and linear regression respectively. Relative to controls, significant elevation of 123I-QNB binding was apparent in the right occipital lobe in DLB and right and left occipital lobes in PDD (height threshold p ≤ 0.001 uncorrected). PDD also showed significant loss in uptake in frontal regions and temporal lobes bilaterally that was not present in DLB. These patterns appeared to be independent of any corresponding rCBF changes. Significant elevation of mAChRs in the occipital lobe was associated with DLB and PDD. This may relate to the visual disturbances that are prevalent in these disorders. Further studies are required in order to establish the role of mAChRs in visual function.