Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis

Background: Psychosis is common in patients with Alzheimer disease. While t he relationship between psychosis and clinical variables has been examined frequently, few studies have examined the relationship between psychosis an d the 2 major neuropathological hallmarks of Alzheimer disease: neurofibril lary tangles and senile plaques. We characterized the occurrence of psychos is in relation to dementia severity and determined if subjects with Alzheim er disease and psychosis had a greater neurofibrillary tangle or senile pla que burden than subjects with Alzheimer disease and no psychosis. Methods: One hundred nine subjects with Alzheimer disease were followed lon gitudinally with semistructured assessments in order to assign a Clinical D ementia Rating and determine whether psychosis was present. After the subje cts died, their brains were obtained for histological examination. Analysis of variance was used to compare the densities of neurofibrillary tangles, total senile plaques, and cored senile plaques in subjects with psychosis v s sub- jects without psychosis, in several neocortical regions, the hippoca mpus, and the entorhinal cortex. Results: Psychosis occured commonly in Alzheimer disease, affecting 63% of subjects. The frequency of psychosis increased with increasing dementia sev erity. More importantly, we found that subjects with psychosis had a 2.3-fo ld (95% confidence interval, 1.2-3.9) greater density of neocortical neurof ibrillary tangles than did subjects without psychosis. The increase was ind ependent of dementia severity. No similar relationship with psychosis was s een for total senile plaques or cored senile plaques. Conclusions: The increase in psychosis frequency that occurs with the progr ession of dementia severity and the independent association between psychos is and neurofibrillary tangle density suggest the possibility that some com mon underlying process or processes specific to Alzheimer disease may regul ate both phenomena.