Detection of MCI may permit intervention that slows the progress of subsequent dementia. 22 MCI subjects (age 71±11) were identified in a retrospective review by a neurologist and a gerontologist of dementia patients who had undergone HMPAO brain SPECT. SPECT was reconstructed with OSEM and attenuation correction. Twelve of the MCI subjects (age 75±6 y) converted to a dementia of Alzheimer's type within five years. The remaining ten MCI subjects (age 67±5 y) did not progress to dementia for at least two years following their scan. Regional cerebral blood flow deficits relative to 24 normal control subjects (age 64±11y) were investigated. Statistical analysis comparing the three groups (MCI converters, stable MCIs and normal controls) was carried out using SPM5 including age as a nuisance covariate, and ISSP/Neurostat. Considerable inter-subject variance was observed amongst the MCI subjects, particularly in the periventricular area. To allow for this, we applied a novel intensity scaling method which systematically excluded voxels with large inter-subject variance when calculating the global scaling factors. Significant hypoperfusion was observed in the anterior cingulate gyrus of the MCI converters compared with the normal controls (corrected P of most significant voxel = 0.016, corrected cluster P = 1.0e-5). No significant differences (corrected P < 0.05) were noted between the MCI converters and stable MCIs. Previous studies report changes elsewhere in the brain but with weaker statistics. Scaling of brain SPECT using regions unaffected by atrophy may permit more accurate characterization of dementia.