Argyrophilic grains are detected as punctate or filiform structures in the neuropil of the medial temporal lobe, and dementia with grains (DG) is defined as a form of dementia with argyrophilic grains as the only explainable cause. We found argyrophilic grains in 43.2% of our 190 serial autopsy brains (mean age, 79.7 yr) from a community-based geriatric hospital, but only 20% of these argyrophilic grain-positive brains fulfilled the criteria for DG. To determine if there are structural differences between cognitively normal cases with argyrophilic grains (CNG) and DG, we studied 14 brains with CNG and 15 brains with DG. All cases of DG had severe atrophy of the ambient gyrus (the junction between temporal lobe and amygdala) with spongiosis, neuronal loss, and gliosis, as well as many grains, pretangles, coiled bodies, and tau-immunoreactive astrocytes. Comparable changes were not present in the ambient gyrus of CNG brains. The temporal neocortex and hippocampus were relatively spared in DG, in contrast to Alzheimer disease. Our study suggests that selective severe involvement of the ambient gyrus may explain the clinical manifestations of a limbic-type dementia in DG.