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Novel Approaches to Understanding the Mechanisms of the Neuropsychiatric Symptoms in Alzheimer’s Disease and Related Dementias (ADRD) and Advancing Therapy Development


Jovier Evans, Ph.D.
Division of Translational Research


This concept aims to encourage research that will enhance knowledge of mechanisms underlying neuropsychiatric symptoms (NPS) in dementia, leading to the development of novel treatments.


The burden of Alzheimer’s disease is compounded by NPS which occur in almost all patients with AD and are usually persistent. NPS are associated with accelerated cognitive and functional decline, worsened quality of life, earlier transition to a nursing home or assisted living facility, and premature mortality. Depression, apathy, anxiety, agitation, and irritability are the most observed NPS. Prior NIMH-supported work supported documented that, despite an FDA black box warning, an increased percentage of older adults with dementia are being prescribed atypical antipsychotic medications, often to address NPS symptoms. Most of these prescriptions are for off-label use1

The widespread use of antipsychotics points to the need to develop better treatments for behavioral symptoms and NPS seen in dementia. Before developing novel treatment options, there is an urgent need to advance the mechanistic understanding of these symptoms in older adults with AD. The National Plan to Address Alzheimer’s Disease  calls specifically for the development of better treatments for the behavioral and psychiatric complications due to the disease and falls within the priorities of the NIMH.

Expected outcomes of this initiative include:

  • Improve our understanding of neurobiological and behavioral mechanisms underlying NPS in ADRD
  • Gather preliminary data in the translational space for further treatment development

1Olfson, M, King, M, & Schoenbaum, M. Antipsychotic Treatment of Adults in the United States (2015)