The relative contribution of Alzheimer disease (AD) hippocampal neuronal pathology in cognitive decline is still matter of debate. To address this issue, we performed a stereologic analysis of layer II of the entorhinal cortex and the CA1 field of the hippocampus in 34 autopsy cases covering the whole spectrum of old age (with 30% of nonagenarians and centenarians) and Clinical Dementia Rating (CDR) scale scores. In both areas, the proportion of NFT-containing neurons increased steadily as a function of the CDR score. Questionable dementia was associated with a 1.9% neuronal loss in the entorhinal cortex and 26% in the CA1 field. NFT numbers predicted only 38% of the neuron number variability in the entorhinal cortex and 55% in the CA1 field. Neuron counts in the entorhinal cortex and both neuron and NFT counts in the CA1 field were significantly associated with cognitive status explaining 25% and 44% of the CDR variability, respectively. Our data reveal a dissociation between the patterns of progression of NFT and neuronal loss in the entorhinal cortex and CA1 field. Moreover, they show that less than 50% of the cognitive variability may be attributable to AD neuronal pathology in these areas.