THE NEUROPATHOLOGICAL CHANGES ASSOCIATED WITH NORMAL BRAIN AGING

Neurofibrillary tangles and senile plaques are common neuropathologica l features in both normal brain aging and Alzheimer's disease. In orde r to examine the patterns of lesion distribution in cerebral aging, we review the clinicopathological analysis of 1144 nondemented cases com paring their neuropathologic features to that reported in cases with m ild cognitive impairment and cases with Alzheimer's disease. Regardles s of cognitive status, layer II of the entorhinal cortex is involved w ith neurofibrillary tangle formation in all of the cases, while the CA 1 field of the hippocampus and the subiculum are less consistently aff ected. Neocortical area 20 is particularly prone to develop neurofibri llary tangles in intellectually preserved elders, whereas other neocor tical areas are relatively spared. Substantial senile plaque formation is seen in the neocortex of non-demented cases. Quantitatively, mild cognitive impairment is correlated with neurofibrillary tangle densiti es in layer II of the entorhinal cortex, and clinically overt Alzheime r's disease with neurofibrillary tangle densities in area 20. In non-d emented centenarians, there is an early development of neurofibrillary tangles in areas usually spared in the course of the degenerative pro cess in younger individuals. These observations demonstrate that mesia l and inferior temporal lobe structures are affected more frequently t han originally thought in normal brain aging. In this respect, neurofi brillary tangle formation in area 20 may represent a crucial step of t he degenerative process, because it may precede the emergence of the n europsychological deficits characteristic of Alzheimer's disease. In a ddition, this study reveals age-related heterogeneity in the regional vulnerability of the cerebral cortex during normal brain aging.