Dementia of the Alzheimer type and related dementias in the aged: DAT subgroups and senile dementia of the neurofibrillary tangle type

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Abstract
The aims of this study are to elucidate variations in the neuropathology of dementia of the Alzheimer's type (DAT) and related dementias in the elderly, and to delineate a senile dementia characterized by abundant neurofibrillary tangles (NFT) in the hippocampal region and by a scarcity of senile plaques (SP) throghout the brain (senile dementia of the NFT type; SD‐NFT) in comparison with usual DAT cases. One hundred and five autopsied patients who developed dementia at age 70–100 years were investigated. The autopsy series included 57 cases of DAT, five of diffuse Lewy body disease (DLBD) with Alzheimer‐tyupe neuropathological changes, and five of SD‐NFT. The 57 DAT patients were classified into three subgroups depending onthe severity of the neocotical neuronal degeneration (NFT and neuronal loss): the diffuse, severe type (DAT‐DS, extensive and severe involvement of the neocortex; n= 18); the diffuse, mild type (DAT‐DM, mild involvement of the neocortex; n= 29); and the localized type (DAT‐L, neuronal degeneration almost localized to the hippocampal region; DAT without neocortical NFT; n= 10). The frequencies of the DAT subgroups, DLBD, and SD‐NFT in each age group at the onset were DAT‐DS (41%) > DAT‐DM (38%) > DLBD (16%) > DAT‐L (6%) of patients in their 70s, DAT‐DM (52%) > DAT‐L (24%) > DAT‐DS (16%) > SD‐NFT (8%) of those in their 80s, and DAT‐DS (40%) > SD‐NFT (30%) > DAT‐L (20%) > DAT‐DS (10%) of those in their 90s and older. In a morphometric comparison with age‐mathced DAT cases, the SD‐NFT showed a significantly higher density of hippocampal NFT and a significant scarcity of SP and cerebral amyloid angiopathy in the brain. Analysis of genotypes of apolipoprotein E gene revealed that no patient with the SD‐NFT had ε4 allele which was shown to be frequently associated with DAT. Our results have indicated (i) that the later onset of DAT and related dementias is linked with the milder neuronal degeneration in the neocortex, and (ii) that the SD‐NFT is a common neuropathological condition that causes dementia in the very aged, in which the pathogenetic process may be different from that in DAT.