title: Apathy in Neurodegenerative Diseases: Recommendations on the Design of Clinical Trials.
abstract: Apathy is a common feature of neurodegenerative disorders but is difficult to study in a clinical trial setting due to practical and conceptual barriers. Principal challenges include a paucity of data regarding apathy in these disorders, an absence of established diagnostic criteria, the presence of confounding factors (eg, coexisting depression), use of concomitant medications, and an absence of a gold-standard apathy assessment scale. Based on a literature search and ongoing collaboration among the authors, we present recommendations for the design of future clinical trials of apathy, suggesting Alzheimer disease and Parkinson disease as models with relevance across a wider array of neuropsychiatric disorders. Recommendations address clarification of the targeted study population (apathy diagnosis and severity at baseline), confounding factors (mood/cognition, behavior, and treatment), outcome measures, study duration, use of comparators and considerations around environment, and the role of the caregiver and patient assent. This review contributes to the search for an optimal approach to study treatment of apathy in neuropsychiatric disorders.
authors: Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA cumminj@ccf.org.
authors: Jeffrey
authors: J
authors: Cummings
authors: Department of Neurology, Movement Disorders Program, Butler Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
authors: Joseph H
authors: JH
authors: Friedman
authors: Clinical Development, Neurosciences, F. Hoffman-La Roche AG, Basel, Switzerland.
authors: George
authors: G
authors: Garibaldi
authors: Bridge Medical Consulting Ltd, London, United Kingdom.
authors: Martin
authors: M
authors: Jones
authors: Clinical Development, Neurosciences, F. Hoffman-La Roche AG, Basel, Switzerland.
authors: Wayne
authors: W
authors: Macfadden
authors: Mental Health Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA Menninger Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Laura
authors: L
authors: Marsh
authors: CoBTeK, Research Memory Center CMRR CHU, University of Sophia Antipolis, Nice, France.
authors: Philippe H
authors: PH
authors: Robert
mesh_terms: D000544:Alzheimer Disease / Q000523:psychology; D057565:Apathy; D002986:Clinical Trials as Topic; D003863:Depression / Q000175:diagnosis / Q000523:psychology; D003866:Depressive Disorder / Q000175:diagnosis / Q000523:psychology; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000150:complications; D012107:Research Design
keywords: Alzheimer disease; Parkinson disease; apathy; trial design