Regional cerebral glucose metabolism (rCMRG1) measured by positron emission tomography of 18F-2-fluoro-2-deoxy-D-glucose was studied longitudinally (interval ranging from 6 to 27 months) in 25 patients with probable Alzheimer's disease (AD). A significant decline of rCMRG1 was noted in the whole brain (p = 0.02) which was most pronounced in the temporoparietal (p = 0.002), frontal (p = 0.01), superior parietal (p = 0.01) and occipital (p = 0.03) association cortex. A similar decline was also present in the thalamus (p = 0.04) but not in the primary visual and sensorimotor cortex, basal ganglia, cerebellum and brainstem. The changes of rCMRG1 in the temporoparietal, frontal and occipital association cortex were related to the change of the Mini Mental State Examination score (temporoparietal: r = 0.49, p = 0.01; frontal: r = 0.40, p = 0.05; occipital: r = 0.44, p = 0.03). The rate of clinical and metabolic decline was not related to age at onset, sex, family history or duration of disease. The results suggest that clinical deterioration and metabolic impairment in probable AD are closely related and dependent on progression of pathological changes in cortical association areas.