Manuscript Region of Origin: UNITED KINGDOM Abstract: Treatments currently licensed for Alzheimer's dementia target cholinergic brain systems. In vivo nicotinic receptor binding may provide an early marker of illness and treatment suitability. In this pilot, we examined nine patients with amnestic mild cognitive impairment (MCI) and ten age and education matched healthy volunteers with high resolution SPECT and the nicotinic receptor ligand 123I-5-IA-85380. Uptake data were analysed using voxel-based techniques for group comparisons and regression analyses with cognitive impairment as covariates. MCI patients had discrete reductions in uptake in medial temporal cortex. Correlations with cognitive impairment were found in left temporo-parietal areas (Addenbrooke's Cognitive Examination) and bilateral temporo-limbic areas (Reye Auditory Verbal Learning Test), and right parahippocampal gyrus (Reye Complex Figure Test) within the patient group. In vivo nicotinic receptor binding appears to be sensitive to brain changes in MCI. Larger scale explorations of patients undergoing treatment will be necessary to evaluate its use in predicting or monitoring treatment response.