Biomarkers of agitation and aggression in Alzheimer's disease: A systematic review

Alzheimers Dement. 2018 Oct;14(10):1344-1376. doi: 10.1016/j.jalz.2018.04.013. Epub 2018 Jun 23.

Abstract

Introduction: Agitation is one of the most challenging neuropsychiatric symptoms to treat in Alzheimer's disease and has significant implications for patient and caregiver. A major source of difficulty in identifying safe and effective treatments for agitation is the lack of validated biomarkers. As such, patients may not be appropriately targeted, and biological response to pharmacotherapy cannot be adequately monitored.

Methods: This systematic review aimed to summarize evidence on the association between biomarkers and agitation/aggression in patients with Alzheimer's disease, utilizing the National Institute on Aging-Alzheimer's Association Research Framework and the Biomarkers, EndpointS, and other Tools Resource of the Food and Drug Association-National Institutes of Health Biomarker Working Group.

Results: This review identified six classes of biomarkers (neuropathological, neurotransmitter, neuroimaging, apolipoprotein E (APOE) genotype, inflammatory, and clusterin) associated with agitation/aggression, which were mostly diagnostic in nature.

Discussion: Future studies should investigate the predictive, prognostic, and monitoring capacity of biomarkers to provide insight into the longitudinal course of agitation/aggression, as well as predict and monitor biological response to a pharmacological intervention.

Keywords: Aggression; Agitation; Alzheimer's disease; Amyloid; Biomarkers; Blood-based; Genetics; Neuroimaging; Neuropathology; Neurotransmitters; Tau.

Publication types

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

MeSH terms

  • Aggression* / physiology
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / psychology
  • Biomarkers / metabolism
  • Humans
  • Psychomotor Agitation / diagnosis*
  • Psychomotor Agitation / genetics
  • Psychomotor Agitation / physiopathology

Substances

  • Biomarkers