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

Am J Geriatr Psychiatry. 2022 Feb;30(2):119-147. doi: 10.1016/j.jagp.2021.06.016. Epub 2021 Jul 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / psychology
  • Apathy*
  • Biomarkers
  • Humans
  • Neurocognitive Disorders

Substances

  • Biomarkers