title: Role of the extended MAPT haplotype in the worsening of psychotic symptoms and treatment response in Alzheimer disease.
abstract: BACKGROUND
  There is evidence that neurofibrillary tangle (NFT) burden is associated with psychotic symptoms in Alzheimer disease (AD). However, it is not clear whether this association is direct or mediated through the increased cognitive impairment associated with NFTs.
  
  
  METHODS
  We sought to determine whether the extended MAPT haplotype was associated with the worsening of delusions and hallucinations in a combined cohort of 95 patients who participated in 2 clinical trials of treatment with memantine.
  
  
  RESULTS
  After controlling for baseline dementia severity, exposure to memantine, and antipsychotics, analysis shows that carriers of at least one H2 allele had a 5.4-fold (P = .03) increased risk of worsening hallucinations. There was some evidence of association with worsening delusions but only in analysis by allele.
  
  
  CONCLUSIONS
  These results are the first to indicate that the H2 allele of the extended MAPT haplotype negatively affects the course of psychotic symptoms in AD independently of disease severity. It will be important for future research to examine MAPT transcription in people with AD with and without psychotic symptoms to understand the exact mechanisms underlying these findings.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK. Electronic address: Byron.Creese@kcl.ac.uk.
authors.forename: Byron
authors.initials: B
authors.lastname: Creese
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Corbett
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Jones
authors.affiliation: Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, Norfolk, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Fox
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003702:Delusions / Q000235:genetics; D018450:Disease Progression; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005260:Female; D006212:Hallucinations / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome; D016875:tau Proteins / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; C054369:MAPT protein, human; D016875:tau Proteins; D008559:Memantine
keywords: Alzheimer disease; Delusions; MAPT; hallucinations; psychosis; tau