NIH R01: Interaction Between Environmental Factors and Lewy Body Dementia

Funding Opportunity Number: PAR-24-249

Letter of Intent: September 4, 2024
Submission: October 4, 2024


LBD is a complex brain disorder that affects more than one million Americans. Most people with LBD are older adults for whom the disorder leads to disabilities in thought and movement. The precise cause of LBD is unknown. LBD can occur alone or along with Alzheimer’s pathology or Parkinson’s disease. The National Institute of Neurological Disorders and Stroke (NINDS leads the NIH research programs in ADRD, including LBD. LBD is associated with abnormal deposits of a protein called alpha-synuclein in the brain. These deposits, called Lewy bodies, affect brain cell function that, in turn, can lead to problems with thinking, movement, behavior, sleep and mood. There are two types of LBD, dementia with Lewy body disease (DLB) and Parkinson’s disease with dementia (PDD). While having a family member with LBD may increase a person’s risk, LBD is not normally considered a genetic disease. At this time, no genetic test can accurately predict whether someone will develop LBD. However, some studies suggest that a healthy lifestyle, including regular exercise, mental stimulation, and a healthy diet, might reduce the chance of developing age-associated dementias. Some researchers are looking at the disease’s underlying biology and genetic risk factors, and it is thought that LBD can arise from the interaction of multiple genes and environmental factors. Environmental risk factors (ERFs) are understudied and there continues to be a need to identify the mechanistic basis for how this gene-environment interaction leads to the formation of Lewy bodies and LBD. This NOFO focuses on the exogenous ERFs that influence LBD and is responsive to the ADRD Milestone titled “Understanding LBD Genetic, Epigenetic, and Environmental Influences“.

Scientific Scope and Research Objectives:

This NOFO will support research that firmly establishes the links between exogenous ERFs and Lewy body disease and formation. Examples of exogenous ERFs responsive to this NOFO are the following:

  • Air pollution: particulate matter, nitrogen oxides, sulfur dioxide, carbon monoxide, and volatile organic compounds
  • Water and Soil Contamination: heavy metals, pathogens, pesticides, and industrial chemicals in drinking water
  • Climate Change: extreme weather events, altered disease patterns, food and water shortages
  • Exposure to Hazardous Chemicals: in everyday products, industrial processes, and waste sites that can pose health risks through exposure via air, water, food, and direct contact with contaminated surfaces
  • Built Environment: Factors such as poor housing conditions, inadequate sanitation, urban sprawl, and lack of green spaces

Studies will include discovery and verification of known exogenous ERFs that affect LBD. Verification of these ERFs should include mechanistic studies on the plausibility that the risk factor(s) has an effect on LBD biology such as effects on Lewy bodies, alpha-synuclein, etc . Mechanistic, translational, and human subject studies on the relation between ERFs and LBD are all responsive to this NOFO. In addition to mechanistic studies, the scope includes research based on clinical data, human samples, and human subjects, but it does not include NIH-defined clinical trials (** We expect successful research proposals will draw expertise from neuroscientists that have deep expertise in basic, translational, and clinical research in LBD and scientists with expertise in exogenous ERFs that can influence the human body.

For more information, please see the announcement webpage.