Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimerdisease

Background: The relationship between neuropathological lesions and mild, "p reclinical," cognitive impairments of Alzheimer disease is poorly understoo d. Identification of the lesions that are most closely associated with the earliest symptoms of Alzheimer disease is crucial to the understanding of t he disease process and the development of treatment strategies to affect it s progression. Design and Main Outcome Measures: We examined the extent of neurofibrillary tangles (NFTs) in 4 neocortical regions, the hippocampus, the entorhinal c ortex, and the amygdala in 65 elderly subjects with no dementia, questionab le dementia, mild dementia, or moderate dementia as assessed using the Clin ical Dementia Rating Scale (CDR). Setting and Patients: Postmortem study of nursing home residents. Results: Neurofibrillary tangles were present in the entorhinal cortex and the hippocampus of all subjects, including those without cognitive deficits . Neocortical NFTs were mostly absent in the nondemented (CDR score, 0.0) s ubjects. The density of NFTs in the questionably demented (CDR score, 0.5) subjects was not significantly increased (P>.20) relative to the nondemente d group in any of the brain regions studied. Significant increases (P<.04) in NFT density become apparent first in the amygdala and the temporal corte x in subjects rated to be mildly impaired (CDR score, 1.0). By the time tha t cognitive impairments were judged to be moderately severe (CDR score, 2.0 ), all regions of the brain examined, except for the occipital cortex, were significantly (P<.05) involved. Conclusions: Some NFTs are present in the entorhinal cortex and hippocampus of most elderly individuals irrespective of their cognitive status, but th e density of NFTs increases as a function of dementia severity.