CLUSTERING OF PATHOLOGICAL FEATURES IN ALZHEIMERS-DISEASE - CLINICAL AND NEUROANATOMICAL ASPECTS

We have analyzed the tendency of amyloid load, neuritic plaques and ne urofibrillary tangles (NFT) in the hippocampus and neocortex to occur in clusters in 49 consecutive cases of Alzheimer's disease (AD). This clustering tendency of the pathology was analysed in relation to sever ity of clinical disease assessed within 6 months before death, duratio n and age at onset of disease and at death. Amyloid plaques showed onl y a slight tendency to cluster together while neuritic plaques and, ev en more, NFT were clearly clustered. A greater clustering tendency was associated with more severe clinical impairment with particularly str ong correlations being found between the clustering tendency of NFT in the hippocampus and clinical memory deficit, and between the clusteri ng tendency of NFT in the parietal neocortex and overall cognitive def icit. Neuritic plaques showed similar but less pronounced and robust c orrelations between clustering and cognitive status. In the hippocampu s NFT clustering was also negatively correlated with age at death, but not duration of disease nor age of disease onset. We conclude that cl ustering characterises neuritic pathology but not diffuse amyloid depo sits and significantly affects cognition. The discrepancies between th e group diagnosed as AD-only and the patient group that contained all patients, including the ones with mixed pathology, lead us to believe that any additional pathology might have a significant effect on the c ognitive status of AD patients.