title: Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis.
abstract: BACKGROUND
  Psychosis is common in patients with Alzheimer disease. While the relationship between psychosis and clinical variables has been examined frequently, few studies have examined the relationship between psychosis and the 2 major neuropathological hallmarks of Alzheimer disease: neurofibrillary tangles and senile plaques. We characterized the occurrence of psychosis in relation to dementia severity and determined if subjects with Alzheimer disease and psychosis had a greater neurofibrillary tangle or senile plaque burden than subjects with Alzheimer disease and no psychosis.
  
  
  METHODS
  One hundred nine subjects with Alzheimer disease were followed longitudinally with semistructured assessments in order to assign a Clinical Dementia Rating and determine whether psychosis was present. After the subjects 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 vs subjects without psychosis, in several neocortical regions, the hippocampus, and the entorhinal cortex.
  
  
  RESULTS
  Psychosis occurred commonly in Alzheimer disease, affecting 63% of subjects. The frequency of psychosis increased with increasing dementia severity. More importantly, we found that subjects with psychosis had a 2.3-fold (95% confidence interval, 1.2-3.9) greater density of neocortical neurofibrillary tangles than did subjects without psychosis. The increase was independent of dementia severity. No similar relationship with psychosis was seen for total senile plaques or cored senile plaques.
  
  
  CONCLUSIONS
  The increase in psychosis frequency that occurs with the progression of dementia severity and the independent association between psychosis and neurofibrillary tangle density suggest the possibility that some common underlying process or processes specific to Alzheimer disease may regulate both phenomena. Arch Gen Psychiatry. 2000;57:1165-1173.
authors: Washington University, Department of Psychiatry, Campus Box 8134, 660 S Euclid Ave, St Louis, MO 63110-1009, USA. farbern@psychiatry.wustl.edu
authors: N B
authors: NB
authors: Farber
authors: E H
authors: EH
authors: Rubin
authors: J W
authors: JW
authors: Newcomer
authors: D A
authors: DA
authors: Kinscherf
authors: J P
authors: JP
authors: Miller
authors: J C
authors: JC
authors: Morris
authors: J W
authors: JW
authors: Olney
authors: D W
authors: DW
authors: McKeel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D015897:Comorbidity; D003702:Delusions / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D006212:Hallucinations / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019579:Neocortex / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology*; D012720:Severity of Illness Index