Revisiting Criteria for Psychosis in Alzheimer’s Disease and Related Dementias: Toward Better Phenotypic Classification and Biomarker Research

Article type: Research Article

Authors: Fischer, Corinne E.^{a; b; 1; *} | Ismail, Zahinoor^{c; 1} | Youakim, James M.^d | Creese, Byron^e | Kumar, Sanjeev^{b; f} | Nuñez, Nicolas^g | Ryan Darby, R.^h | Di Vita, Antonella^{i; j} | D’Antonio, Fabriziaⁱ | de Lena, Carloⁱ | McGeown, William J.^k | Ramit, Ravona^{l; m} | Rasmussen, Jillⁿ | Bell, Joanne^o | Wang, Huali^p | Bruneau, Marie-Andrée^q | Panegyres, Peter K.^r | Lanctôt, Krista L.^{b; s} | Agüera-Ortiz, Luis^t | Lyketsos, Constantine^u | Cummings, Jeffrey^v | Jeste, Dilip V.^w | Sano, Mary^x | Devanand, D.P.^y | Sweet, Robert A.^z | Ballard, Clive^e

Affiliations: [a] Keenan Research Centre for Biomedical Research, St. Michael’s Hospital, Toronto, Canada | [b] Department of Psychiatry, University of Toronto, Toronto, Canada | [c] Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences; Hotchkiss Brain Institute and O’Brien Institute for Public Health, University of Calgary, Calgary, Canada | [d] ACADIA Pharmaceuticals Inc., Princeton, NJ, USA | [e] Medical School, College of Medicine and Health, University of Exeter, Exeter, UK | [f] Centre for Addiction and Mental Health, Toronto, Canada | [g] Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA | [h] Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA | [i] Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy | [j] Department of Psychology, Sapienza University of Rome, Rome, Italy | [k] School of Psychological Sciences and Health, University of Strathclyde, Glasgow, UK | [l] Memory and Geriatric Psychiatry Clinic, Sheba Medical Center, Tel Hashomer, Israel | [m] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel | [n] Psi-Napse, Surrey, UK | [o] Syneos Health, Wilmington, NC, USA | [p] Dementia Care and Research Center, Peking University Institute of Mental Health (Sixth Hospital), National Clinical Research Center for Mental Disorders, Beijing, China | [q] Department of Psychiatry, University of Montreal, Centre de Recherche de l’Institut Universitaire de gériatrie de Montréal (CRIUGM), Montreal, Canada | [r] Director, Neurodegenerative Disorders Research Pty Ltd, West Perth, WA, Australia | [s] Hurvitz Brain Sciences Research, Sunnybrook Health Sciences Centre, Toronto, Canada | [t] Department of Psychiatry Instituto de Investigación Sanitaria (imas12), Hospital Universitario 12 de Octubre, & Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain | [u] Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview, Johns Hopkins Medicine, Baltimore, MD, USA | [v] UNLV Department of Brain Health and the Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA | [w] Departments of Psychiatry and Neurosciences, and Stein Institute for Research on Aging, University of California San Diego, San Diego, CA, USA | [x] Mt Sinai School of Medicine, Manhattan, NY, USA | [y] Department of Psychiatry, Columbia University, New York City, NY, USA | [z] Departments of Psychiatry and Neurology, University of Pittsburgh, PA, USA

Correspondence: [*] Correspondence to: Dr. Corinne Fischer, Room 17-044 cc Wing, St. Michael’s Hospital, 30 Bond St., Toronto, Ontario, M5B 1W8, Canada. Tel.: +1 416 864 5320; E-mail: [email protected]

Note: [1] Denotes primary co-authors.

Abstract: Background:Psychotic symptoms are common in Alzheimer’s disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice. Objective:To establish research criteria for the diagnosis of psychosis in AD. Methods:The International Society to Advance Alzheimer’s Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria. Results:Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers. Conclusion:We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.

Keywords: Alzheimer’s disease, criteria, delusions, hallucinations, mild cognitive impairment, psychosis

DOI: 10.3233/JAD-190828

Journal: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 1143-1156, 2020