Original Study| Volume 15, ISSUE 12, P934-937, December 2014

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Role of the Extended MAPT Haplotype in the Worsening of Psychotic Symptoms and Treatment Response in Alzheimer Disease

Published:October 08, 2014DOI:



      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.


      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.


      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.


      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.


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      • Erratum
        Journal of the American Medical Directors AssociationVol. 16Issue 3
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          The authors would like to make a correction to the Acknowledgments section of their article which appeared in the December 2014 issue:
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