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Applying Quantitative Systems Pharmacology Methods to Study Psychosis in Alzheimer’s Disease

Peihao, Fan (2023) Applying Quantitative Systems Pharmacology Methods to Study Psychosis in Alzheimer’s Disease. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Psychosis is surprisingly common in Alzheimer disease (AD) and can emerge as a part of the neurodegenerative disease process in advance of dementia during the mild cognitive impairment stage or even earlier. Approximately 50% of Alzheimer’s disease patients will develop psychotic symptoms, e.g. hallucination and delusions, and these patients will experience more severe cognitive decline compared with those without psychosis. However, no medication has been approved by the Food and Drug Administration for treating psychosis in AD (AD+P) and second-generation antipsychotics are widely used in clinical practice with modest efficacy and elevated adverse events rate. It is critical to explore and propose more effective and safer treatment options to treat AD+P. Some important advances in recent years provided us opportunities in connecting and comparing the neuropsychiatric symptoms (NPS) in AD with other neurological disorders which will greatly help us understand its mechanisms and further develop appropriate treatments for AD+P. In this thesis, the journey of understanding AD+P starts at comparing it with the similar psychotic symptoms in schizophrenia. We found that the similar psychotic symptoms in AD+P and schizophrenia are supported by distinct genetic associations and pathways which also provided a possible explanation for the decreased efficacy and increased adverse events rate of antipsychotics in AD+P. Multiple approaches, classic and innovative, were applied to identify critical risk factors and possible protective roles in the advancement of AD+P. With the information we have acquired about AD+P from the previous studies, state-of-the-art quantitative systems pharmacology (QSP) approaches are applied to explore and propose alternative treatment options for AD+P. We found out that antidepressants showed a possible beneficial effect against AD+P and they exert their effect through different pathways with antipsychotics which allowed them to form a synergetic effect that may improve therapeutic efficacy or lower the risk of side effects.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Peihao, Fanpef14@pitt.edupef140000-0002-9814-5085
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLevent,
Committee MemberRobert,
Committee MemberJunmei,
Committee MemberRobert,
Thesis AdvisorLirong,
Date: 3 April 2023
Date Type: Publication
Defense Date: 20 March 2023
Approval Date: 3 April 2023
Submission Date: 22 March 2023
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 242
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Alzheimer's Disease; Psychosis; Systems pharmacology; Antipsychotics; Real-world evidence
Date Deposited: 03 Apr 2023 13:32
Last Modified: 03 Apr 2023 13:32


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