The purpose of the present study was to validate the use of tissue radioactivity ratios instead of regional metabolic rates for the assessment of regional metabolic changes in Alzheimer's disease(AD) with [18F]FDG PET and to examine the correlation of ratio indices with the severity of cognitive impairment in AD. Thirty-seven AD patients(age 68±9 yrs, mean±s.d.; 36 probable and 1 definite AD), 28 patients with dementia of non-Alzheimer type(age 66±7 yrs), and 17 healthy controls(age 66±4 yrs) underwent [18F]FDG PET imaging. Two simplified radioactivity ratio indices were calculated from 37-66 min image: region-to-cerebellar radioactivity-ratio(RCR) and a composite radioactivity ratio(a ratio of radioactivity in the most typically affected regions over the least typically affected regions: CRR). Local cerebral metabolic rate for glucose(LCMRglu) was also measured using a three-compartment, five-parameter tracer kinetic model. The ratio indices were significantly lower in AD patients than in controls(RCR in temporoparietal cortex, 0.949±8.136 vs. 1.238±0.129, p=0.0004; PCR in frontal cortex, 1.027±0.128 vs. 1.361±0.151, p〈0.0001; CRR, 0.886±0.096 vs. 1.032±0.042: p=0.0024). On the RCR analysis, 86% of AD patients showed a pattern of bilateral temporoparietal hypometabolism with or without frontal involvement; hypometabolism was unilateral in 11% of the patients. When bilateral temporoparietal hypometabolism was considered to be suggestive of AD, the sensitivity and specificity of the RCR was analysis for the differential diagnosis of AD were 86% and 73%, respectively. The RCR was correlated significantly with the macroparameter K [K1k3/(k2+k3)] (r=0.775, p〈0.0001) and LCMRglu(r=0.633, p=0.0002) measured using the kinetic model. In patients with AD, both average RCR of cortical association areas and CRR were correlated with Mini-Mental Status Examination(r=0.565, p=0.0145; r=0.642, p=0.0031, respectively), Clinical Dementia Rating(r=-0.576, p=0.0124; r=-0.591, p=0.0077), and total score of Mattis Dementia Rating Scale (r=0.574, p=0.0648; r=0.737, p=0.0096). There were also significant correlations between memory and language impairments and corresponding regionl RCRs. The results suggest that the [18F]FDG PET ratio indices, RCR and CRR, reflect global and regional metabolic rates and correlate with the severity of cognitive impairment in AD. The simplified ratio analysis may be clinically useful for the differential diagnosis and seral monitoring of the disease.