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Acknowledgements: We thank the Alzheimer’s Society, the Newcastle Healthcare Charity, the Medical Research Council UK [grant number G9817682], the NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge and the NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. We thank staff at the Regional Medical Physics Department, Department of Nuclear Medicine, Newcastle General Hospital for undertaking SPECT scanning and all members of the clinical research team who helped with patient recruitment and assessment. ; BACKGROUND: Cholinergic dysfunction, particularly involving nicotinic acetylcholine receptors (nAChRs), contributes to cognitive and psychiatric symptoms in dementia with Lewy bodies (DLB), yet spatial covariance patterns remain unexplored. We aimed to characterise these patterns using 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) SPECT (α4β2 nAChR assessment) and examine their association with cognitive function. METHODS: Fifteen DLB and 16 healthy controls underwent 1235IA-85380 and rCBF 99mTc-exametazime SPECT scanning. Voxel principal components analysis (PCA), generated PC images representing common intercorrelated voxels across subjects. Linear regression identified α4β2 nAChR and rCBF patterns distinguishing DLB from controls. RESULTS: A distinct α4β2 nAChR pattern differentiated DLB from controls (F1,29 = 165.1, p < 0.001), that was dissimilar to rCBF changes. This pattern was characterised by decreased uptake in temporal pole, inferior frontal cortex, amygdala, olfactory cortex, insula, anterior/mid cingulate, and putamen, alongside preserved/increased uptake in sensorimotor cortex, fusiform and occipital lobe. These regions mapped onto default, salience, limbic, frontostriatal, sensorimotor and visual hubs. We then derived from patients, α4β2 nAChR patterns that correlated with CAMCOGtotal (r = - 0.52, p = 0.04), MMSE (r = - 0.68, p = ... |