Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials


Moyra E. Mortby, School of Psychology, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia. Electronic address: m.mortby@unsw.edu.au.
Lawrence Adler, Clinical Insights, Inc., Maryland, MD.
Luis Agüera-Ortiz, 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.
Daniel R. Bateman, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN; Regenstrief Institute, Inc., Indiana University Center for Aging Research, Indianapolis, IN.
Henry Brodaty, Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Sydney, Australia.
Marc Cantillon, Department of Psychiatry, Robert Wood Johnson Medical School, New Brunswick, NJ.
Yonas E. Geda, Alzheimer's Disease and Memory Disorder's Program, Department of Neurology, Barrow Neurological Institute, Phoenix, AZ.Follow
Zahinoor Ismail, Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, Hotchkiss Brain Institute, and O'Brien Institute of Public Health, University of Calgary, Calgary, Canada.
Krista L. Lanctôt, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute and Departments of Psychiatry and Pharmacology/Toxicology, University of Toronto, Toronto, Canada.
Gad A. Marshall, Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Prasad R. Padala, Geriatric Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR.
Antonios Politis, Division of Geriatric Psychiatry, First Department of Psychiatry, National and Kapodistrian University of Athens, Athens, Greece.
Paul B. Rosenberg, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD.
Kostas Siarkos, Division of Geriatric Psychiatry, First Department of Psychiatry, National and Kapodistrian University of Athens, Athens, Greece.
David L. Sultzer, Institute for Memory Impairments and Neurological Disorders (UCI MIND), and Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine CA.
Christos Theleritis, Division of Geriatric Psychiatry, First Department of Psychiatry, National and Kapodistrian University of Athens, Athens, Greece.

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Apathy is one of the most prevalent, stable and persistent neuropsychiatric symptom across the neurocognitive disorders spectrum. Recent advances in understanding of phenomenology, neurobiology and intervention trials highlight apathy as an important target for clinical intervention. We conducted a comprehensive review and critical evaluation of recent advances to determine the evidence-based suggestions for future trial designs. This review focused on 4 key areas: 1) pre-dementia states; 2) assessment; 3) mechanisms/biomarkers and 4) treatment/intervention efficacy. Considerable progress has been made in understanding apathy as a treatment target and appreciating pharmacological and non-pharmacological apathy treatment interventions. Areas requiring greater investigation include: diagnostic procedures, symptom measurement, understanding the biological mechanisms/biomarkers of apathy, and a well-formed approach to the development of treatment strategies. A better understanding of the subdomains and biological mechanisms of apathy will advance apathy as a treatment target for clinical trials.

Medical Subject Headings

Alzheimer Disease (drug therapy, psychology); Apathy; Biomarkers; Humans; Neurocognitive Disorders

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The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry







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