R01NS129934

Cerebral autoregulation, brain perfusion, and neurocognitive outcomes after traumatic brain injury (CAPCOG-TBI) - project summary.

Traumatic brain injury (TBI) is a leading cause of disability in adults and the quality of life of TBI survivors is highly dependent on the adequacy of cognitive recovery. TBI is also a risk factor for Alzheimer's disease (AD) and AD-related dementias (ADRD). Mounting evidence indicates that cerebrovascular dysfunction occurs in both TBI and AD/ADRD and can be a cross-link between the two diseases.

The 2019 ADRD summit called for further studies to understand vascular contributions to progressive cognitive impairment/dementia associated with TBI and develop non-invasive diagnostic approaches. The following important knowledge gaps exist:

1) What is the impact of early cerebrovascular dysfunction after TBI on short and long-term cognitive outcomes after accounting for age, sex, and pre-existing health conditions?

2) What is the temporal relationship between the cerebrovascular function recovery and cognitive outcome after TBI?

3) Is there a relationship between cerebrovascular dysfunction and post-TBI neurodegeneration?

The overarching goal of this proposal is to determine whether acute cerebrovascular dysfunction and its recovery within the first year post-injury are associated with cognitive outcomes and neurodegeneration 12 months after moderate to severe TBI (MSTBI). Our central hypothesis is that cerebrovascular function measured by dynamic cerebral autoregulation (CA) and brain perfusion during the acute stage and its recovery during the first year are inversely associated with cognitive outcomes and brain volume loss at 12 months post-injury.

We propose a longitudinal study with 100 adults who sustained a single MSTBI and 30 controls with non-TBI orthopedic trauma in the first week after the initial injury. We will follow them at 3 months, 6 months, and 12 months after injury. The primary outcome will be the NIH Toolbox Cognitive Battery fluid composite score supplemented with sensitive episodic memory and processing speed measures at 12 months post-injury.

To address the overarching goal, we aim to:

1) Determine the association of cerebrovascular dysfunction during the acute stage of MSTBI (<1-week post-injury) with cognitive outcome at 1 year. CA will be quantified by dynamic changes in arterial blood pressure and cerebral blood flow velocity or brain tissue oxygenation. Brain perfusion will be determined by the sum of cerebral blood flow measured from the bilateral internal carotid artery and vertebral artery.

2) Determine the temporal association between the recovery of cerebrovascular function and cognitive outcomes after TBI. CA and brain perfusion will be measured at 3, 6, and 12 months post-injury.

3) Determine the temporal associations of acute cerebrovascular dysfunction and its recovery with the imaging biomarkers of neurodegeneration after TBI over time. Multimodal MRI studies will be performed at 3 months and 12 months post-injury.

The findings from this study will improve our understanding of cerebrovascular contributions to cognitive outcome and neurodegeneration after TBI. The knowledge obtained will provide critical data to inform the development of strategies based on vascular mechanisms to improve cognition and slow neurodegeneration after TBI.

The University Of Texas Southwestern Medical Center

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Texas United States

State-Wide

Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional) (PA-20-272)

Amendment Since initial award the total obligations have increased 304% from $839,689 to $3,393,269.