To determine the extent of neurodegeneration of the visual association cortex, we assessed hyperphosphorylated tau-immunoreactive (HPtau-IR) neurofibrillary tangles in Brodmann Areas 18/19 in nondemented and demented subjects. At least occasional HPtau-IR neurofibrillary tangles were seen in 24% of 59 nondemented subjects with ages at death ranging from 42 to 87 years. The incidence increased to 41% in the 32 nondemented subjects who had HPtau-IR pathology in the hippocampal region. Demented subjects with Braak Stages 0 to III and corticobasal degeneration, frontotemporal lobar degeneration with TAR DNA binding protein 43, vascular cognitive impairment, or dementia with Lewy bodies also had HPtau-IR pathology in Brodmann Areas 18/19. These results support the concept that the occipital association area may have enhanced vulnerability to neurodegeneration. Neuropathologic assessment of these areas is, therefore, recommended, particularly in subjects suspected or known to have had mild cognitive impairment. Occasional HPtau-IR lesions were also seen in the medial temporal gyrus. Thus, the question as to whether scattered HPtau-IR lesions in either temporal or occipital cortex indicate a neurodegenerative disease remains unresolved. Further systematic clinicopathologic studies are needed for an understanding of regional susceptibility to neurodegeneration and the significance of scattered HPtau-IR brain lesions.