OBJECTIVE: A subgroup of patients with Alzheimer's disease present with visual disturbances at onset. This study investigated whether specific cortical networks associated with visual processes are preferentially affected in this subgroup and determined the clinical implications of such abnormalities. METHOD: Regional cerebral glucose metabolic rates were assessed with positron emission tomography and [18F]2-fluoro-2- deoxy-D-glucose, and general intellectual functions, memory, and visual skills were measured with cognitive tests in patients with probable Alzheimer's disease-10 with and 22 without prominent visual symptoms- and in 25 healthy comparison subjects. RESULTS: Both patient groups showed reduced glucose metabolism in parietal regions and in middle and superior temporal regions in comparison with the healthy subjects. The Alzheimer's disease patients without visual symptoms also showed reductions in inferior temporal, frontal, and limbic structures, as is typical of Alzheimer's disease. In contrast, the patients with visual symptoms had larger metabolic deficits than the patients without visual symptoms in the parietal and occipital cortices (including the primary visual cortex), with a relative sparing of inferior temporal, frontal, and limbic regions. Consistently, the patients with visual symptoms had significantly greater visuospatial deficits and less severe memory impairments than the patients without visual symptoms. CONCLUSIONS: Alzheimer's disease patients with visuospatial deficits who are studied while alive have a distinctive regional distribution of cerebral metabolic impairment that is related to specific cognitive deficits and that distinguishes them from patients with typical Alzheimer's disease. These findings imply that regional variations in brain dysfunction can occur in Alzheimer's disease, with differential involvement of cortical systems resulting in distinctive clinical subgroups.