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Principal Investigator: Benjamin L Brett
Organization: MEDICAL COLLEGE OF WISCONSIN
Fiscal Year: 2024
Award: $132,171
Funding agency: National Institute on Aging
Project Summary/Abstract (1 page)
Exposure to mild traumatic brain injury (mTBI) and repetitive head impacts (RHI) during sport participation has
been associated with adverse long-term consequences (e.g., cognitive decline). Research investigating these
associations has been limited to cross-sectional studies at single points of the lifespan without consideration of
factors that can influence these associations. Greater mTBI/RHI history is associated with cerebral blood flow
(CBF) and white matter (WM) abnormalities, even within younger athletes. CBF and WM abnormalities are two
indicators of pathological aging and longitudinal decline in the general population. Age and cardiovascular risk
factors across the lifespan can influence these abnormalities. The scientific objective of this proposal is to
determine the influence of mTBI/RHI on MRI metrics of pathological aging and neurobehavioral function across
the lifespan. Our central hypothesis is that mTBI/RHI will be associated with neurobehavioral function and
CBF/WM abnormalities, and that the strength of this association is independently influenced by increasing age
and the presence of cardiovascular risk factors. The rationale for this project is that determining the influence
of mTBI/RHI on MRI metrics of pathological aging and neurobehavioral function across the lifespan, as well as
factors that influence this relationship, will provide insight into the process underlying cumulative head injury
and neurological decline later in life. Our hypothesis will be tested with two specific and one exploratory aims:
1) Determine the associations between mTBI/RHI and neurobehavioral function across the lifespan and the
influence of comorbid cardiovascular risk factors; 2) Determine the associations between mTBI/RHI and MRI
metrics of pathological aging across the lifespan and the influence of comorbid cardiovascular risk factors;
Exploratory) Examine if MRI metrics of pathological aging mediate the association between cumulative
mTBI/RHI and neurobehavioral function across the lifespan. To establish an independent research program
that identifies the mechanisms by which mTBI/RHI can result in long-term neurological disease burden, the
training objective of this proposal is to receive expert training/mentorship in a) the analysis and interpretation of
neuroimaging data, b) the cumulative effects of aging and cardiovascular risk factors on long-term brain health
and function, and c) the molecular mechanisms and progression of neuropathology as a consequence of
mTBI/RHI. We will employ an innovative lifespan approach by leveraging data from four large-scale,
prospective, multi-center studies of athletes across several decades of life. Harmonization of several mentor-
directed, large-scale multisite datasets of athletes will allow a hybrid prospective, cross-sectional design. We
will utilize advanced analytical approaches to examine the potential influence of aging and comorbid
cardiovascular risk factors on the associations between mTBI/RHI with MRI metrics of pathological aging and
long-term neurobehavioral changes. This work is significant in that it will inform methods for identifying those at
risk for decline, improve risk estimates of long-term outcomes, and inform therapeutic targets for intervention.
Terms: <0-11 years old><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Active Follow-up><Age><Aged 65 and Over><Aging><Anisotropy><Anxiety><Award><Behavior Conditioning Therapy><Behavior Modification><Behavior Therapy><Behavior Treatment><Behavioral Conditioning Therapy><Behavioral Modification><Behavioral Therapy><Behavioral Treatment><Blood Vessels><Brain Concussion><Cerebral Concussion><Cerebrovascular Circulation><Child><Child Youth><Children (0-21)><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Commotio Cerebri><Conditioning Therapy><Craniocerebral Injuries><Craniocerebral Trauma><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><DWI (diffusion weighted imaging)><DWI-MRI><Data><Data Set><Degenerative Neurologic Disorders><Diet><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Disease Frequency Surveys><Disturbance in cognition><ED visit><ER visit><Emergency care visit><Emergency department visit><Emergency hospital visit><Emergency room visit><Exposure to><General Population><General Public><Goals><Head Injuries><Head Trauma><Health><Health behavior><History><Hybrids><Impaired cognition><Intervention><Intervention Strategies><Life><MR Imaging><MR Tomography><MRI><MRIs><MTBI><Magnetic Resonance Imaging><Mediating><Mediation><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Memory><Mental Depression><Mentors><Mentorship><Methods><Mission><Molecular><Multi-center studies><Multicenter Studies><NIH><NMR Imaging><NMR Tomography><National Institutes of Health><Nature><Negotiating><Negotiation><Nervous System Degenerative Diseases><Nervous System Diseases><Nervous System Disorder><Neural Degenerative Diseases><Neural degenerative Disorders><Neurobiology><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic><Neurologic Degenerative Conditions><Neurologic Disorders><Neurological><Neurological Disorders><Nuclear Magnetic Resonance Imaging><Outcome><Pathway interactions><Physical activity><Position><Positioning Attribute><Preventative intervention><Process><Public Health><Radial><Radius><Recording of previous events><Recurrence><Recurrent><Research><Risk><Risk Estimate><Risk Factors><Role><Severities><Site><Sports><Symptoms><Testing><Therapeutic Intervention><Training><United States><United States National Institutes of Health><Validation><White Matter Hyperintensity><Work><Zeugmatography><aberrant aging><abnormal aging><above age 65><active followup><advanced analytics><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated effects><age effect><age of 65 years onward><age related effects><aged 65 and greater><aged 65+><aged ≥65><ages><aging effect><arterial spin labeling><arterial spin tagging><behavior intervention><behavioral intervention><blood flow in brain><brain blood circulation><brain blood flow><brain health><burden of disease><burden of illness><cardiovascular risk><cardiovascular risk factor><cerebral blood flow><cerebral circulation><cerebrocirculation><cerebrovascular blood flow><co-morbid><co-morbidity><cognitive dysfunction><cognitive loss><cohort><collision sports><comorbidity><concussion><concussive><contact sports><dMRI><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><depression><design><designing><diets><diffusion tensor imaging><disease burden><dysfunctional age related change><dysfunctional aging><executive control><executive function><follow up><follow-up><followed up><followup><head impact><health related behavior><histories><human old age (65+)><impact of age><impaired aging><improved><influence of age><innovate><innovation><innovative><insight><intervention for prevention><intervention therapy><interventional strategy><kids><large scale data><large scale data sets><large scale datasets><life span><lifespan><maladaptive aging><mild TBI><mild brain trauma><mild traumatic brain injury><neural imaging><neuro-imaging><neurobehavioral><neurobiological><neurodegenerative illness><neuroimaging><neurological disease><neurological imaging><neuropathologic><neuropathological><neuropathology><old age><over 65 years><pathological age related changes><pathological aging><pathway><prevention intervention><preventional intervention strategy><preventive intervention><processing speed><programs><prospective><public health relevance><social role><substantia alba><therapeutic agent development><therapeutic development><therapeutic target><validations><vascular><white matter><youngster><≥65 years>