Alzheimer's Disease-Related Dementias Summit 2022: National research priorities for the investigation of post-traumatic brain injury Alzheimer's Disease and Related Dementias.

Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD pathologies including multiple etiology dementia (MED). The National Institutes of Health hosts triennial ADRD Summits to inform a national research agenda, and TBI was included for a second time in 2022. A multidisciplinary expert panel of TBI and dementia researchers was convened to re-evaluate the 2019 research recommendations for understanding TBI as an AD/ADRD risk factor and assess current progress and research gaps in understanding post-TBI AD/ADRD. Refined and new recommendations were presented during the MED special topic session at the virtual ADRD Summit in March 2022. Final research recommendations incorporating broad stakeholder input are organized into four priority areas as follows: (1) Promote interdisciplinary collaboration and data harmonization to accelerate progress of rigorous, clinically meaningful research; (2) Characterize clinical and biological phenotypes of PTND associated with varied lifetime TBI histories in diverse populations to validate multimodal biomarkers; (3) Establish and enrich infrastructure to support multimodal longitudinal studies of individuals with varied TBI exposure histories and standardized methods including Common Data Elements for antemortem and postmortem clinical and neuropathological characterization; and (4) Support basic and translational research to elucidate mechanistic pathways, development, progression and clinical manifestations of post-TBI AD/ADRDs. Recommendations conceptualize TBI as a contributor to MED and emphasize the unique opportunity to study AD/ADRD following known exposure to inform disease mechanisms and treatment targets for shared common AD/ADRD pathways.

[1]  C. Keene,et al.  Traumatic Brain Injury and Risk of Neurodegenerative Disorder , 2021, Biological Psychiatry.

[2]  L. Berkman,et al.  You say tomato, I say radish: can brief cognitive assessments in the US Health Retirement Study be harmonized with its International Partner Studies? , 2020, The journals of gerontology. Series B, Psychological sciences and social sciences.

[3]  Virginia M. Y. Lee,et al.  High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer’s and Non-Alzheimer’s Disease Tauopathies , 2020, Neuron.

[4]  B. Eapen,et al.  Validity of early-onset dementia diagnoses in VA electronic medical record administrative data , 2020, The Clinical neuropsychologist.

[5]  Lilah M. Besser,et al.  Failure to detect an association between self-reported traumatic brain injury and Alzheimer's disease neuropathology and dementia , 2019, Alzheimer's & Dementia.

[6]  A. Murzin,et al.  Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules , 2019, Nature.

[7]  David L. Kaplan.  Causal Inference for Observational Studies. , 2018, The Journal of infectious diseases.

[8]  D. Rubin,et al.  Early-Stage Non-Small Cell Lung Cancer: Quantitative Imaging Characteristics of (18)F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis. , 2016, Radiology.

[9]  F. Hammond,et al.  Traumatic brain injury as a chronic health condition. , 2013, Archives of physical medicine and rehabilitation.

[10]  Victoria E. Johnson,et al.  Chronic neuropathologies of single and repetitive TBI: substrates of dementia? , 2013, Nature Reviews Neurology.

[11]  Douglas H. Smith,et al.  Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease? , 2010, Nature Reviews Neuroscience.

[12]  J. Trojanowski,et al.  Brain Trauma in Aged Transgenic Mice Induces Regression of Established Aβ Deposits , 2000, Experimental Neurology.

[13]  K. Cicerone,et al.  Definition of mild traumatic brain injury , 1993 .

[14]  OUP accepted manuscript , 2021, Research Evaluation.

[15]  Lee S. Tirrell,et al.  Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies , 2018, Journal of neuropathology and experimental neurology.