The Late Effects of Traumatic Brain Injury (LETBI) study aims to identify predictors, clinical phenotypes, imaging biomarkers, and histopathological signatures of neurodegenerative disease in patients with traumatic brain injury (TBI).  TBI is widely recognized as a risk factor for Alzheimer’s disease and related dementias (AD/ADRDs), but the mechanisms through which it initiates or exacerbates clinical and/or pathological Alzheimer’s or ADRD features (e.g., cortical volumetric changes, tau [T-tau, pTau], beta amyloid [aβ42/40]) are unknown. The LETBI study will elucidate the clinical signatures, mechanisms, and pathobiology of post-traumatic ADRDs (PT-ADRD) by distinguishing clinically significant cognitive decline from static cognitive impairment following head trauma in an enriched longitudinal sample of patients characterized with clinical and biological metrics of high relevance for Alzheimer’s and related dementia phenotyping. By applying advanced statistical methods, novel neuroimaging processing, ultra-sensitive single molecule array technology, and state-of-the-art neuropathology methods, we will identify clinical features and mechanistic biomarkers of PT-ADRD that can be used to improve ADRD diagnosis and inform new targets for disease-modifying therapies.

Edlow BL, Keene CD, Perl DP, Iacono D, Folkerth RD, Stewart W, Mac Donald CL, Augustinack J, Diaz-Arrastia R, Estrada C, Flannery E, Gordon WA, Grabowski TJ, Hansen K, Hoffman J, Kroenke C, Larson EB, Lee P, Mareyam A, McNab JA, McPhee J, Moreau AL, Renz A, Richmire K, Stevens A, Tang CY, Tirrell LS, Trittschuh EH, van der Kouwe A, Varjabedian A, Wald LL, Wu O, Yendiki A, Young L, Zöllei L, Fischl B, Crane PK, Dams-O’Connor K.  Multimodal characterization of the late effects of traumatic brain injury: A methodological overview of the Late Effects of Traumatic Brain Injury Project. Journal of Neurotrauma. 2018;35:1604-1619. PMCID PMC6016096. [PubMed]

Kenney K, Iacono D, Edlow BL, Katz DI, Diaz-Arrastia R, Dams-O’Connor K, Daneshvar DH, Stevens A, Moreau AL, Tirrell LS, Varjabedian A, Yendiki A, van der Kouwe A, Mareyam A, McNab JA, Gordon WA, Fischl B, McKee AC, Perl DP.  Dementia after moderate-severe traumatic brain injury: Coexistence of multiple proteinopathies.  Journal of Neuropathology and Experimental Neurology. 2018;77:50-63. PMCID PMC5939622. [PubMed] [Altmetric]

Iacono D, Lee P, Edlow BL, Gray N, Fischl B, Kenney K, Lew HL, Lozanoff S, Liacouras P, Lichtenberger J, Dams-O’Connor K, Cifu D, Hinds SR, Perl DP. Early-onset dementia in war veterans: Brain polypathology and clinico-pathological complexity. Journal of Neuropathology and Experimental Neurology. 2020;79:144-162. PMCID PMC6970453. [PubMed] [Altmetric]

Stewart W, Allinson K, Al-Sarraj A, Bachmeier C, Barlow K, Belli A, Burns MP, Carson A, Crawford F, Dams-O’Connor K, Diaz-Arrastia R, Dixon CE, Edlow BL, Ferguson S, Fischl B, Folkerth RD, Gentleman S, Giza CC, Grady MS, Helmy A, Herceg M, Holton JL, Howell D, Hutchinson PJ, Iacono D, Iglesias JE, Ikonomovic MD, Johnson VE, Keene CD, Kofler JK, Koliatsos VE, Lee EB, Levin H, Lifshitz J, Ling H, Loane DJ, Love S, Maas AIR, Marklund N, Master CL, McElvenny DM, Meaney DF, Menon DK, Montine TJ, Mouzon B, Mufson EJ, Ojo JO, Prins M, Revesz T, Ritchie CW, Smith C, Sylvester R, Tang CY, Trojanowski JQ, Urankar K, Vink R, Wellington C, Wilde EA, Wilson L, Yeates K, Smith DH.  Primum non nocere: a call for balance when reporting on CTE. Lancet Neurology. 2019;18:231-233. [PubMed] [PlumX]