Brain perfsion SPECT shows typical regional perfusion abnormalities in Alzheimer's disease(AD) and is useful for its diagnosis. However, there is also arguement that these patterns show significant overlap with other causes, and the accuracy for SPECT in differentiating AD has shown conflicting results. We postulate that the variation in reported results are partly due to a difference in patient or control selection with specia reference to the mixture of ischemic cerebral disease in the atudied poulation. To determine the effect of ischemic lesions and the nature of control subjects on SPECT studies for AD, we performed 99mTc-HMPAO single photon emission computed tomography(SPECT) in 11 probable AD patients with a low (<4) Hachinski ischemic score and 12non-demented age matched controls. Magnetic resonance imaging(MRI) disclosed ischemic cerebral lesions in 27%(3/11) of the PAD group and 25%(3/12) of the control group. Regional perfusion indices were quantitated from the SPECT images as follows and the distribution of perfusion indices from both groups were compared. This was repeated with controls after excluding those with significant ischemic lesions by MRI: regional perfusion index=average regional count/average cerebellar coung All PAD patients showed perfusion abnormality in SPECT. However, 83% (10/12)of controls also showed perfusion abnormalities, and no pattern could reliably differentiate the two groups. After excluding controls with significant cerebral ischemia, the difference in temporal and perietal perfusion index was increased. A decreased temporo- parietal and any parietal or temporal perfusion index had a sensitivity of 18% and 36% in detecting AD, respectively. When using a separate group of normal age mathced controls, the indices showed an even more difference in the temporal and parietal lobes and the sensitivity of a decreased temporoparietal and any parietal or temporal perfusion index had a sensitivity of 36% and 55% in detecting AD, respectively. Thus, the type of control with special reference to the presence of ischemic cerebral lesions contribute significantly to the accuracy of perfusion SPECT in diagnosing AD. This may have particular importance in the diagnosis of AD in populations where the prevalance of cerebrovascular disease in high.