NEOCORTICAL NEUROFIBRILLARY TANGLES CORRELATE WITH DEMENTIA SEVERITY IN ALZHEIMERS-DISEASE

Objective: To determine the relationships between dementia severity an d the extent of histopathologic lesions in a variety of brain regions. Neocortical and hippocampal ratings for neurofibrillary tangles (NFTs ) and senile plaques (SPs) were compared in 70 cases of clinically and neuropathologically confirmed Alzheimer's disease. Design: Neuropatho logic case series. Dementia severity was assessed by postmortem chart review with use of the extended Clinical Dementia Rating Scale (CDR). Linear association between CDR scores and NFT and SP scores were asses sed by partial correlation, controlling for age at death. Setting: Stu dies were conducted at the Alzheimer's Disease Research Center of the Mount Sinai Medical Center, New York, NY. Main Outcome Measure: Associ ation between CDR scores and neuropathologic changes assessed with the Consortium to Establish a Registry for Alzheimer's Disease semiquanti tative scale. Results: Among these lesion scores, only NFTs showed a s ignificant association with CDR score, and only for neocortical region s. In particular, NFT densities in the superior temporal cortex were m ost strongly correlated with dementia severity, followed by those in t he inferior parietal and midfrontal cortex. No such correlations were apparent for the amygdala, hippocampus, or entorhinal cortex. Medial t emporal lobe structures displayed high NFT scores, even in cases of mi ld dementia. Senile plaques did not correlate significantly with CDR s core in any region. Conclusions: These data support the notion that ne ocortical neuronal degeneration, as indicated by NFT formation, is a c ritical determinant of the clinical progression of Alzheimer's disease and suggest that medial temporal lobe structures may represent the in itial site of NFT formation. While SP density correlates with age at d eath, there is no correlation between SP counts and dementia severity. These results further suggest that the clinical presentation of demen tia may be closely related to neurodegeneration in neocortical regions within the temporal lobe.