As the US population ages, the burden of illness due to dementia continues to grow at an alarming rate.  This year the US taxpayer, through their representatives in the Congress, have appropriated an additional $425 million for Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) research to the National Institute on Aging (NIA).  NINDS, working in close partnership with NIA, is the lead NIH Institute for much of the research on ADRD that include frontotemporal, Lewy body, and vascular dementias.  The generous investment in dementia research in fiscal year (FY) 2019 will bring exciting opportunities– to support additional investigator-initiated AD/ADRD research projects within the extended NIH AD/ADRD payline and to launch a number of ambitious, multi-site research efforts that can advance our goal of decreasing one’s risk of dementia and potentially treating some forms of dementia.

Some of you may remember the message I wrote last year to share new ADRD research concepts in advance of official Funding Opportunity Announcements (FOAs).  Thanks to the dedicated work of NINDS program and review staff, and the outstanding research proposals we received, many of those research concepts turned into multiple awards supporting exciting projects in FY 2018.  A long-standing cohort study of over 30,000 participants, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, added a new research focus on vascular contributions to cognitive Impairment and dementia (VCID) to improve understanding of geographic and racial disparities in cardio-/cerebrovascular risk factors and their relationship to cognitive impairment and dementia.  Since many modifiable vascular risk factors can be effectively managed, this is an emerging area of research with significant potential to make headway in prevention strategies.  This past summer, researchers of the Systolic Blood Pressure Intervention Trial - Memory and Cognition In Decreased Hypertension (SPRINT-MIND) study – funded by multiple Institutes at NIH – released preliminary findings that suggest intensive lowering of blood pressure may reduce the risk of developing mild cognitive impairment (MCI) and the combined risk of MCI and dementia.  

For FY 2019, we have already released two ADRD research opportunities – Lewy Body Dementia (LBD) Center without Walls and AD/ADRD Research Supplements to Promote Diversity in Health-Related Research.  We are also planning to re-issue the ADRD PET Ligand Center without Walls.  What else is coming up this year?  For those who may be planning new research proposals and others who follow dementia research at NIH, here is a sneak peek at additional research concepts that are being considered for potential funding opportunities in FY 2019.

• Development and Validation of Advanced Mammalian Models for ADRD: This concept would support studies that will develop improved mammalian models of Lewy body, frontotemporal, vascular, and mixed dementia that recapitulate comprehensive disease phenotypes to advance disease-mechanistic research and therapeutic target discovery. These animal models will be expected to exhibit the broad range of features of the corresponding dementia disorder, including phenotypes during adulthood that can inform research to understand disease progression in humans.
• Next Generation Human Cellular Model Systems for ADRD: This concept would solicit studies to develop, characterize and validate innovative human cellular model systems that recapitulate phenotypic, mechanistic and neuropathological hallmarks of ADRD, similar to the mammalian model research concept described above.  The overall goal would be to establish next generation human cellular model systems for ADRD to serve as tools to interrogate molecular disease mechanisms and identify potential therapeutic targets.
• Clinical Research on Defining and Differential Diagnosis of Chronic Traumatic Encephalopathy (CTE) Contributing to Dementia: This concept would solicit research to identify and validate clinical and biological measures for the diagnosis of dementia due to CTE. The development of CTE diagnostics and cognitive outcomes has been based primarily on a single on-going study of athletes. This research concept aims to support studies that conduct assessments and cross-validate relevant biomarkers in the general population. Studies could further explore how exposure to differential amounts and severities of brain trauma contributes to risk profiles for AD/ADRD, which could in the long term could inform the development of a TBI-dementia risk stratification algorithm with an index for TBI exposure. 
• AD/ADRD Pathology in Dementia with Chronic Effects of Traumatic Brain Injury (TBI): This concept would support research to define and differentiate the neuropathological course of neurodegenerative disease associated with long-term exposure to repetitive head impacts and single/multiple TBI(s) in individuals with cognitive impairment and dementia.  Research focus could include defining postmortem diagnosis for CTE and  CTE mixed with Alzheimer’s or other pathology, developing a digital resource for distribution and sharing of neuropathological tissue, outlining the prevalence of chronic effects of neurotrauma using existing AD/ADRD brain tissue repositories, and determining the incidence of neuropathological co-morbidities in CTE cases. 
• Natural History and Biomarker Development for frontotemporal lobar degeneration (FTLD): This concept would support clinical trial readiness in FTD by studying the natural history of the disease spectrum and facilitating the development of sensitive clinical assessments and biomarkers that can measure changes in disease progression.  
• Functional Validation of Novel Targets in ADRD This concept would support the comprehensive validation of newly identified therapeutic target candidates so that they can be primed for translational research and drug discovery.  In its initial phase, this concept would support the development of customized technologies, models, and protocols to modulate the expression or activity of target candidates in cells or tissues and monitor their functional consequences in in vitro or in vivo disease models.  In the second phase, the validation process that follows the NIH rigor and reproducibility guidelines will carefully and reproducibly measure the impact of the target modulation in different modalities across collaborating laboratories. 
• Progression Markers for Cognitive Impairment in Parkinson’s Disease Dementia (PDD) This concept would stimulate research to identify risk factors for progression of cognitive dysfunction in PDD, with an overall goal to improve the diagnosis of PDD during life.  Research areas of interest include identification of clinical, pathological, and/or biological factors that predict which patients with Parkinson’s disease will 1) experience progressive cognitive deterioration, 2) progress more rapidly or slowly, or 3) develop aberrant behavioral or psychotic symptoms.  Researchers will be encouraged to leverage existing resources from longitudinal cohorts of PDD patients.
• Post-Stroke Vascular Contributions to Cognitive Impairment and Dementia (VCID) in the U.S. Including in Health Disparities Populations: This concept would establish a large prospective clinical research study of individuals in the U.S. who have had a recent stroke, including populations with known disparities in health outcomes.  The goal of the study would be to determine the specific subsets of stroke events that do or do not cause cognitive impairment and dementia, and to identify other clinical factors and comorbidities that may synergize with stroke to contribute to cognitive impairment and dementia.

These AD/ADRD research concepts and funding opportunities are informed by the research recommendations that result from ADRD Summits, one of our major research planning efforts at NINDS. Like the AD Summits and the Dementia Care Summits led by NIA, ADRD Summits take place every three years to revise and reprioritize recommendations based on the scientific progress and needs of the dementia community.  The next ADRD Summit is in March 2019, and we would like to hear from you on what you think are the most important needs and promising opportunities for ADRD research through a Request for Information (RFI): Soliciting Input on Priorities and Progress in ADRD Research (Deadline: December 20, 2018).  Please also remember to save the date (March 14-15, 2019) and register to attend the Summit.

Saturday, December 1, 2018