Role of the extended MAPT haplotype in the worsening of psychotic symptoms and treatment response in Alzheimer disease.
INTRODUCTION
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.


CONCLUSION
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.
['Creese|Byron|B|', 'Corbett|Anne|A|', 'Jones|Emma|E|', 'Fox|Chris|C|', 'Ballard|Clive|C|']
D000368:Aged D000483:Alleles D000544:Alzheimer Disease D014150:Antipsychotic Agents D003702:Delusions D018450:Disease Progression D018691:Excitatory Amino Acid Antagonists D005260:Female D006212:Hallucinations D006239:Haplotypes D006801:Humans D008297:Male D008559:Memantine D011618:Psychotic Disorders D016896:Treatment Outcome D016875:tau Proteins
MAPT Alzheimer disease Delusions hallucinations psychosis tau