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The aim of the study was to evaluate an observer-independent semiquantitative analysis of brain imaging by single-photon emission computed tomography (SPECT) in patients with Alzheimer''s disease (AD). Patients (n = 45, mean age 70 ± 11 years) with a clinical diagnosis of AD according to NINCDS/ADRDA criteria were examined by ^99mTc-ethylcysteine dimer SPECT. Following anatomic normalization and data extraction using three-dimensional stereotactic surface projection, a pixelwise comparison of ECD uptake was performed with the reference values of 10 cognitive intact controls of comparable age. The global relative decrease of cerebral blood flow in cortical association areas showed a significant inverse association with the overall level of cognitive functioning as assessed with the Mini Mental State Examination and with the cognitive section (CAMCOG) of the Cambridge Mental Disorders of the Elderly Examination. There were significant region-specific associations between left temporoparietal perfusion deficit and language performance and between right temporoparietal regional cerebral blood flow reduction and praxis. The results suggest that this observer-independent analysis of SPECT data provides a valid assessment of the pattern and severity of cortical perfusion abnormalities in patients with AD.