Early detection of Alzheimer's disease (AD) allows timely pharmacological and social interventions. Alteration in muscarinic receptor binding was evaluated with I-123 iodo-dexetimide (IDEX) in early clinical stage AD. We studied 11 mild AD patients (Folstein Minimental State Examination Score 24-27, Clinical Dementia Rating 0.5-1.0) and 10 age- and sex-matched normal subjects with SPECT brain imaging after injection of 185 MBq of IDEX and 750 MBq of 99mTc-HMPAO. Using a voxel based approach (Statistical Parametric Mapping (SPM99) software), a deficit in IDEX binding was found in the posterior cingulate cortex in the mild AD group with p (corrected)=0.06 for the most significant voxel and p=0.0003 for the voxel cluster. Region of interest (ROI) analysis confirmed the SPM99 results. SPM99 found no deficit in the HMPAO scans, suggesting that neither atrophy nor hypoperfusion were major factors in the reduced IDEX binding. This study provides further evidence of the involvement of the posterior cingulate region and of muscarinic receptors in early Alzheimer's disease and suggests that this change may precede an alteration in blood flow.