Psychosis as a treatment target in dementia : a roadmap for designing interventions

Agüera-Ortiz, Luis and Babulal, Ganesh M. and Bruneau, Marie-Andrée and Creese, Byron and D’Antonio, Fabrizia and Fischer, Corinne E. and Gatchel, Jennifer R. and Ismail, Zahinoor and Kumar, Sanjeev and McGeown, William J. and Mortby, Moyra E. and Nuñez, Nicolas A. and de Oliveira, Fabricio F. and Pereiro, Arturo X. and Ravona-Springer, Ramit and Rouse, Hillary J. and Wang, Huali and Lanctôt, Krista L. (2022) Psychosis as a treatment target in dementia : a roadmap for designing interventions. Journal of Alzheimer's Disease, 88 (4). pp. 1203-1228. ISSN 1875-8908 (https://doi.org/10.3233/jad-215483)

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Abstract

Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials.

  • Item type:Article
    ID code:81560
    Dates:
    Date
    Event
    16 August 2022
    Published
    1 July 2022
    Published Online
    4 June 2022
    Accepted
    Notes:Funding Information: Sanjeev Kumar has received support from Academic Scholars Award from the Department of Psychiatry, University of Toronto, Brain and Behavior Foundation, National institute on Ageing, BrightFocus Foundation, Brain Canada, Canadian Institute of Health Research, Canadian Consortium on Neurodegeneration in Aging, Centre for Ageing and Brain Health Innovation, Centre for Addiction and Mental Health, University of Toronto. Equipment support from Soterix Medical. Funding Information: Moyra E. Mortby has received support from the Australian National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) Dementia Research Development Fellowship #1102028. Funding Information: Fabricio Oliveira has received support from FAPESP –The State of São Paulo Research Foundation (grant #2015/10109-5). Funding Information: Nicolas A. Nuñez has received support from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685. Funding Information: Jennifer Gatchel has received research support from the BrightFocus Foundation, Alzheimer’s Association, and NIH/NIA. Funding Information: Krista L. Lanctôt has received support from the Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, National Institute on Ageing, Canadian Institutes of Health Research, Weston Brain Institute and the Canadian Consortium on Neurodegeneration in Aging. Funding Information: Ganesh M. Babulal receives research support from the BrightFocus Foundation (A2021142S), and NIH/NIA (R01AG074302 AG068183, AG067428, AG056466). Publisher Copyright: © 2022 - The authors. Published by IOS Press.
    Subjects:Medicine > Internal medicine > Neuroscience. Biological psychiatry. Neuropsychiatry
    Medicine
    Department:Strategic Research Themes > Health and Wellbeing
    Faculty of Humanities and Social Sciences (HaSS) > Psychological Sciences and Health > Psychology
    Depositing user: Pure Administrator
    Date deposited:25 Jul 2022 13:14
    Last modified:09 Apr 2024 03:23
    URI:https://strathprints.strath.ac.uk/id/eprint/81560
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