Back to Journals » Neuropsychiatric Disease and Treatment » Volume 10

Optimal treatment of Alzheimer’s disease psychosis: challenges and solutions

Authors Koppel J, Greenwald B

Received 9 September 2014

Accepted for publication 7 October 2014

Published 24 November 2014 Volume 2014:10 Pages 2253—2262


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Roger Pinder

Jeremy Koppel,1,2 Blaine S Greenwald2

1The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System, Manhasset, NY, USA; 2Zucker Hillside Hospital, Hofstra North Shore-Long Island Jewish School of Medicine, Glen Oaks, NY, USA

Abstract: Psychotic symptoms emerging in the context of neurodegeneration as a consequence of Alzheimer’s disease was recognized and documented by Alois Alzheimer himself in his description of the first reported case of the disease. Over a quarter of a century ago, in the context of attempting to develop prognostic markers of disease progression, psychosis was identified as an independent predictor of a more-rapid cognitive decline. This finding has been subsequently well replicated, rendering psychotic symptoms an important area of exploration in clinical history taking – above and beyond treatment necessity – as their presence has prognostic significance. Further, there is now a rapidly accreting body of research that suggests that psychosis in Alzheimer’s disease (AD+P) is a heritable disease subtype that enjoys neuropathological specificity and localization. There is now hope that the elucidation of the neurobiology of the syndrome will pave the way to translational research eventuating in new treatments. To date, however, the primary treatments employed in alleviating the suffering caused by AD+P are the atypical antipsychotics. These agents are approved by the US Food and Drug Administration for the treatment of schizophrenia, but they have only marginal efficacy in treating AD+P and are associated with troubling levels of morbidity and mortality. For clinical approaches to AD+P to be optimized, this syndrome must be disentangled from other primary psychotic disorders, and recent scientific advances must be translated into disease-specific therapeutic interventions. Here we provide a review of atypical antipsychotic efficacy in AD+P, followed by an overview of critical neurobiological observations that point towards a frontal, tau-mediated model of disease, and we suggest a new preclinical animal model for future translational research.

Keywords: Alzheimer’s disease, antipsychotics, psychosis, tau, behavioral disturbance, agitation

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]