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

Moyra E Mortby¹, Lawrence Adler², Luis Agüera-Ortiz³, Daniel R Bateman⁴, Henry Brodaty⁵, Marc Cantillon⁶, Yonas E Geda⁷, Zahinoor Ismail⁸, Krista L Lanctôt⁹, Gad A Marshall¹⁰, Prasad R Padala¹¹, Antonios Politis¹², Paul B Rosenberg¹³, Kostas Siarkos¹², David L Sultzer¹⁴, Christos Theleritis¹²; ISTAART NPS PIA

Affiliations

¹ School of Psychology, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia. Electronic address: m.mortby@unsw.edu.au.
² Clinical Insights, Inc., Maryland, MD.
³ 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.
⁴ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN; Regenstrief Institute, Inc., Indiana University Center for Aging Research, Indianapolis, IN.
⁵ Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Sydney, Australia.
⁶ Department of Psychiatry, Robert Wood Johnson Medical School, New Brunswick, NJ.
⁷ Alzheimer's Disease and Memory Disorder's Program, Department of Neurology, Barrow Neurological Institute, Phoenix, AZ.
⁸ Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, Hotchkiss Brain Institute, and O'Brien Institute of Public Health, University of Calgary, Calgary, Canada.
⁹ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute and Departments of Psychiatry and Pharmacology/Toxicology, University of Toronto, Toronto, Canada.
¹⁰ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
¹¹ Geriatric Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR.
¹² Division of Geriatric Psychiatry, First Department of Psychiatry, National and Kapodistrian University of Athens, Athens, Greece.
¹³ Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD.
¹⁴ Institute for Memory Impairments and Neurological Disorders (UCI MIND), and Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine CA.

PMID: 34315645
DOI: 10.1016/j.jagp.2021.06.016

Free article

Review

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

Moyra E Mortby et al. Am J Geriatr Psychiatry. 2022 Feb.

Free article

. 2022 Feb;30(2):119-147.

doi: 10.1016/j.jagp.2021.06.016. Epub 2021 Jul 1.

Authors

Affiliations

¹ School of Psychology, University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia. Electronic address: m.mortby@unsw.edu.au.
² Clinical Insights, Inc., Maryland, MD.
³ 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.
⁴ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN; Regenstrief Institute, Inc., Indiana University Center for Aging Research, Indianapolis, IN.
⁵ Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Sydney, Australia.
⁶ Department of Psychiatry, Robert Wood Johnson Medical School, New Brunswick, NJ.
⁷ Alzheimer's Disease and Memory Disorder's Program, Department of Neurology, Barrow Neurological Institute, Phoenix, AZ.
⁸ Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, Hotchkiss Brain Institute, and O'Brien Institute of Public Health, University of Calgary, Calgary, Canada.
⁹ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute and Departments of Psychiatry and Pharmacology/Toxicology, University of Toronto, Toronto, Canada.
¹⁰ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
¹¹ Geriatric Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR.
¹² Division of Geriatric Psychiatry, First Department of Psychiatry, National and Kapodistrian University of Athens, Athens, Greece.
¹³ Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD.
¹⁴ Institute for Memory Impairments and Neurological Disorders (UCI MIND), and Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine CA.

PMID: 34315645
DOI: 10.1016/j.jagp.2021.06.016

Abstract

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.

Keywords: ISTAART neuropsychiatric syndromes professional interest area; apathy; assessment; future directions; mechanisms and biomarkers; neurocognitive disorders; pre-dementia states; treatment and intervention; treatment target.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest MEM, LA, LA-O, DRB, HB, YG, GAM, PRP, AP, KS report no conflicts with any product mentioned or concepts discussed in this article. ZI has received consultation funding from Otsuka/Lundbeck, outside the submitted work. MC has received consultation funding from Allergan, Kyowa, Reviva, Sunovion and Otsuka. HB has received consultation funding from Nutricia Australia and Biogen. KLL has received consultation fees from BioXcel, Cerevel, Eisai, Kondor, Otsuka and Praxis, outside of the submitted work. PBR has received research funding support outside of this project from Lilly, Vaccinex, National Institute on Aging, Alzheimer’s Association, Functional Neuromodulation (FNMI), Lilly, Alzheimer’s Disease Cooperative Study (ADCS), Alzheimer’s Disease Trials Research Institute (ATRI), Alzheimer’s Clinical Trials Consortium (ACTC), Richman Family Precision Medicine Center of Excellence on Alzheimer’s Disease. PBR has received income from consulting, advisory boards, and/or DSMB from GLG, Leerink, Cerevel, Cerevance, Bioxcel, Sunovion, Acadia, Food and Drug Administration, Medalink, Novo Nordisk, Noble Insights, and Synaptogen. DLS has received research support from NIH and Eisai, has participated as a paid member of a DSMB or adjudication committee with Acadia, Avanir, Janssen, and Otsuka, and has received consulting fees from Avanir and NovoNordisk (all unrelated to apathy treatment).

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical