NIH – Clinical and Biological Measures of TBI-related Dementia Including Chronic Traumatic Encephalopathy (R01 Clinical Trial Not Allowed)

August 20, 2021 by


This FOA invites investigation of biological and clinical measures of TBI-related progressive neurodegeneration and neurocognitive decline associated with increased risk for dementia and /or traumatic encephalopathy syndrome (TES) (clinicopathologic diagnostic counterpart to the neuropathological diagnosis of Chronic Traumatic Encephalopathy (CTE)). Investigations should be based on existing, well-characterized populations of patients with a history of TBI that are enriched for increased risk of cognitive impairment or dementia and can continue to be followed longitudinally; additional subjects may be recruited as appropriate. The overall goal is to advance knowledge of the underlying pathophysiology and clinical characterization of the chronic effects of TBI that distinguish static-chronic TBI cognitive impairment from those that lead to progressive neurodegeneration associated with TES and dementia. A critical feature of this FOA includes the broad sharing of clinical, neuroimaging, physiological, and biospecimen data and to create a data and associated biofluid resource for the broader community to further advance research in this area.


In recent years, there has been a resurgence of both research and public interest in the long-term consequence of TBI, particularly as it relates to neurodegeneration, all-cause dementia and Chronic Traumatic Encephalopathy (CTE). Epidemiological data suggest that a history of traumatic brain injury (TBI) is a significant risk factor for Alzheimer’s Disease (AD) and Alzheimer’s Disease Related Dementias (ADRD) and that the relative risk may be mediated by injury severity and frequency with increased severity and multiple insults resulting in higher risk. Frequency and severity of injury also contribute to the heterogenous expression of chronic static TBI-induced neurocognitive and neuropsychiatric sequelae. For example, more severe injuries often result in long-term static neurocognitive impairments that contribute to overall disability. However, the lack of selective and sensitive tools to differentiate the chronic static TBI-induced sequelae from progressive neurocognitive dysfunction can confuse the risk of dementia following TBI. Similarly, while TBI likely incurs risk for multiple progressive neurodegenerative paths, neither the diagnostic tools nor biomarkers exist to distinguish the potential risk for any specific neurodegenerative path. To date, the best characterized association may be the relationship between frequency of brain injury with postmortem CTE. Recently, initial diagnostic criteria have been published , for Traumatic Encephalopathy Syndrome (TES; CTE in living persons), however, these criteria require continued development and additional data for improving differential diagnoses. Advancing diagnostics of TBI-related neurodegeneration and associated cognitive impairment, including TES, through the discovery and validation of novel and existing tools has the potential to improve understanding of TBI’s contribution to risk for specific dementias which could lead to improved clinical care and patient stratification in future clinical trials.

Key Dates:

October 10, 2021
Letter of Intent Due Date(s): October 10, 2021
Application Due: November 10, 2021

URL for more information:

Filed Under: Funding Opportunities