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11 - Late Effects

from Part II - Outcomes after Concussion

Published online by Cambridge University Press:  22 February 2019

Jeff Victoroff
Affiliation:
University of Southern California, Torrance
Erin D. Bigler
Affiliation:
Brigham Young University, Utah
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Summary

The history of medical observation is unknown. Astute medical conclusions that self-evidently must have been divined by Australopithecines have yet to be unearthed. One can only presume that, sometime in the last 10 million years, some species became conscious of the fact that concussive brain injury (CBI) often has late effects. More recently, largely due to significant increases in life expectancy after 1900, it has become clear that traumatic brain injuries -- single or multiple -- very often have disabling effects that either persist after injury or appear after a symptomatic caesura. Another relatively modern observation is that, with the passing of time, the waning of vigor, and the accumulation of mutations, old brains change in ways very roughly correlatable with behavioral functionality. What remains profoundly mysterious is whether and how these two observations relate. This chapter essays a slightly ambitious agenda: to consider the late effects of one or more CBIs in the light of basic principles of biology and logic. It is proposed that only by examining time-passing-related brain change free of implausible preconceived nosologies might one devise research strategies that can illuminate that relationship.
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Concussion and Traumatic Encephalopathy
Causes, Diagnosis and Management
, pp. 496 - 554
Publisher: Cambridge University Press
Print publication year: 2019

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References

Freibaum, BD, Lu, Y, Lopez-Gonzalez, R, Kim, NC, Almeida, S, Lee, KH, et al. GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 2015; 525: 129–33.CrossRefGoogle ScholarPubMed
Stacey, D, Ciobanu, LG, Baune, BT. A systematic review on the association between inflammatory genes and cognitive decline in non-demented elderly individuals. Eur Neuropsychopharmacol 2015; 27 (6): 568–88.Google ScholarPubMed
Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine. Definition of mild traumatic brain injury. J Head Trauma Rehabil 1993; 8: 8687.CrossRefGoogle Scholar
Bird, A, Tobin, E. Natural kinds. In: Zalta, EN (ed.) The Stanford encyclopedia of philosophy. Stanford, CA. Updated 02/17/2017. Available at: https://plato.stanford.edu/entries/natural-kinds/.Google Scholar
Surján, G. The cultural history of medical classifications. In: Barriers and challenges of using medical coding systems. 2011. Available at http://dare.uva.nlGoogle Scholar
Carroll, L. What the tortoise said to Achilles. Mind 1895; 104: 691–693.Google Scholar
James, W. Lecture 1: religion and neurology. New York: Longmans, Green, 1902.Google Scholar
Mill, JS. A system of logic, ratiocinative and inductive: being a connected view of the principles of evidence, and the methods of scientific investigation. London: John W. Parker, 1843.Google Scholar
Smith, EE, Medin, DL. Categories and concepts. Cambridge, MA: Harvard University Press, 1981.Google Scholar
Smith, JD, Zakrzewski, AC, Johnson, JM, Jeanette, C, Valleau, JC. Ecology, fitness, evolution: new perspectives on categorization. Curr Direct Psychol Sci 2016; 25: 266274.Google Scholar
Kruglanski, AW, Webster, DM, Klem, A. Motivated resistance and openness to persuasion in the presence or absence of prior information. J Pers Soc Psychol 1993; 65: 861–76.Google Scholar
Webster, DM, Kruglanski, AW. Individual differences in need for cognitive closure. J Pers Soc Psychol 1994; 67: 1049–62.Google Scholar
Budner, S. Intolerance of ambiguity as a personality variable. J Pers 1962; 30: 2950.Google Scholar
Biasi, V, Bonaiuto, P, Levin, JM. Relation between stress conditions, uncertainty and incongruity intolerance, rigidity and mental health: experimental demonstrations. Health (N Y) 2015; 7: 71.Google Scholar
Hochmann, JR, Mody, S, Carey, S. Infants’ representations of same and different in match- and non-match-to-sample. Cogn Psychol 2016; 86: 87111.Google Scholar
Aristotle, . Posterior analytics. 350 B.C. http://classics.mit.edu/Aristotle/posterior.html.Google Scholar
Hawley, K, Bird, A. What are natural kinds? Philosoph Perspect 2011; 25: 205–21.Google Scholar
Quran. Surah Al-Baqarah [verse 187].Google Scholar
Perusini, G. Über klinisch und histologisch eigenartige psychische Erkrankungen des späteren Lebensalters. Histologische und Histopathologische Arbeiten. Jena: Gustav Fischer Verlag Jena, 1909, pp. 297351.Google Scholar
Darwin, C. The descent of man and selection in relation to sex. London: John Murray, 1871, p. 6.Google Scholar
Freeman, SH, Kandel, R, Cruz, L, Rozkalne, A, Newell, K, Frosch, MP, et al. Preservation of neuronal number despite age-related cortical brain atrophy in elderly subjects without Alzheimer disease. J Neuropathol Exp Neurol 2008; 67: 1205–12.CrossRefGoogle ScholarPubMed
American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5), 5th edition. Washington, DC: American Psychiatric Publishing, 2013.Google Scholar
Goldberg, D. Plato versus Aristotle: categorical and dimensional models for common mental disorders. Compr Psychiatry 2000; 41: 813.Google Scholar
Schotte, CK, Maes, M. Descriptive diagnostic assessment of depression: categorical diagnosis, dimensional assessment, and instruments. Acta Neuropsychiatr 2001; 13: 212.CrossRefGoogle ScholarPubMed
Rosenman, S, Korten, A, Medway, J, Evans, M. Dimensional vs. categorical diagnosis in psychosis. Acta Psychiatr Scand 2003; 107: 378–84.Google Scholar
Kraemer, HC, Noda, A, O’Hara, R. Categorical versus dimensional approaches to diagnosis: methodological challenges. J Psychiatr Res 2004; 38: 1725.CrossRefGoogle ScholarPubMed
Huprich, SK, Bornstein, RF. Dimensional versus categorical personality disorder diagnosis: implications from and for psychological assessment. J Pers Assess 2007; 89: 12.Google Scholar
Abrams, DJ, Rojas, DC, Arciniegas, DB. Is schizoaffective disorder a distinct categorical diagnosis? A critical review of the literature. Neuropsychiatr Dis Treat 2008; 4: 1089–109.Google ScholarPubMed
McGrath, RE, Walters, GD. Taxometric analysis as a general strategy for distinguishing categorical from dimensional latent structure. Psychol Methods 2012; 17: 284–93.Google Scholar
De Beurs, E, Barendregt, M, Rogmans, B, Robbers, S, Van Geffen, M, Van Aggelen-Gerrits, M, et al. Denoting treatment outcome in child and adolescent psychiatry: a comparison of continuous and categorical outcomes. Eur Child Adolesc Psychiatry 2015; 24: 553–63.Google Scholar
Yee, CM, Javitt, DC, Miller, GA. Replacing DSM categorical analyses with dimensional analyses in psychiatry research: the research domain criteria initiative. JAMA Psychiatry 2015; 72: 1159–60.Google Scholar
Heinz, A, Schlagenhauf, F, Beck, A, Wackerhagen, C. Dimensional psychiatry: mental disorders as dysfunctions of basic learning mechanisms. J Neural Transm (Vienna) 2016; 123: 809–21.Google ScholarPubMed
Hagele, C, Schlagenhauf, F, Rapp, M, Sterzer, P, Beck, A, Bermpohl, F, et al. Dimensional psychiatry: reward dysfunction and depressive mood across psychiatric disorders. Psychopharmacology (Berl) 2015; 232: 331–41.Google Scholar
Volkmar, FR, McPartland, JC. Moving beyond a categorical diagnosis of autism. Lancet Neurol 2016; 15: 237–8.Google Scholar
Khachaturian, ZS. Diagnosis of Alzheimer’s disease. Arch Neurol 1985; 42: 1097–105.Google Scholar
Best, B. Mechanism of aging. 2016. www.benbest.com/lifeext/aging.html.Google Scholar
Bulterijs, S, Hull, RS, Bjork, VC, Roy, AG. It is time to classify biological aging as a disease. Front Genet 2015; 6: 205.Google Scholar
Kertzer, DI. Aging in the past: demography, society, and old age. Berkeley, CA: University of California Press, 1995.Google Scholar
Weismann, A, Poulton, EB, Schönland, S, Shipley, AE. Essays upon heredity and kindred biological problems, 2nd edition. Oxford: Clarendon Press, 1891.Google Scholar
Medawar, PB. An unsolved problem of biology. London: for the College by H.K. Lewis, 1952.Google Scholar
Williams, GC. Pleiotropy, natural selection and the evolution of senescence. Evolution 1957; 11: 398411.Google Scholar
Ungewitter, E, Scrable, H. Antagonistic pleiotropy and p53. Mech Ageing Dev 2009; 130: 1017.Google Scholar
Alexander, DM, Williams, LM, Gatt, JM, Dobson-Stone, C, Kuan, SA, Todd, EG, et al. The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades. Biol Psychol 2007; 75: 229–38.Google Scholar
Mondadori, CR, De Quervain, DJ-F, Buchmann, A, Mustovic, H, Wollmer, MA, Schmidt, CF, et al. Better memory and neural efficiency in young apolipoprotein E ε4 carriers. Cereb Cortex 2006; 17: 1934–47.Google Scholar
Han, SD, Bondi, MW. Revision of the apolipoprotein E compensatory mechanism recruitment hypothesis. Alzheimers Dement 2008; 4: 251–4.CrossRefGoogle ScholarPubMed
Zetterberg, H, Alexander, DM, Spandidos, DA, Blennow, K. Additional evidence for antagonistic pleiotropic effects of APOE. Alzheimers Dement 2009; 5: 75.Google Scholar
Tuminello, ER, Han, SD. The apolipoprotein E antagonistic pleiotropy hypothesis: review and recommendations. Int J Alzheimers Dis 2011; 2011.Google ScholarPubMed
Jochemsen, HM, Muller, M, Van Der Graaf, Y, Geerlings, MI. APOE ε4 differentially influences change in memory performance depending on age. The SMART-MR study. Neurobiol Aging 2012; 33 (832): e15e22.Google Scholar
Jasienska, G, Ellison, PT, Galbarczyk, A, Jasienski, M, Kalemba-Drozdz, M, Kapiszewska, M, et al. Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy? Proc R Soc Lond B: Biol Sci 2015; 282: 20142395.Google Scholar
Kirkwood, TB. Evolution of ageing. Nature 1977; 270: 301–4.Google Scholar
Libertini, G. An adaptive theory of increasing mortality with increasing chronological age in populations in the wild. J Theor Biol 1988; 132: 145–62.Google Scholar
Libertini, G. Empirical evidence for various evolutionary hypotheses on species demonstrating increasing mortality with increasing chronological age in the wild. Sci World J 2008; 8: 182–93.Google Scholar
Libertini, G. Phylogeny of age-related fitness decline in the wild and of related phenomena. Evol Interpret Aging, Dis Phenom Sex 2011; 92.Google Scholar
Skulachev, VP. Aging is a specific biological function rather than the result of a disorder in complex living systems: biochemical evidence in support of Weismann’s hypothesis. Biochem N Y– Engl Transl Biokhimiya 1997; 62: 1191–5.Google Scholar
Skulachev, VP. Phenoptosis: programmed death of an organism. Biochemistry (Mosc) 1999; 64: 1418–26.Google Scholar
Mitteldorf, J. Ageing selected for its own sake. Evol Ecol Res 2004; 6: 937–53.Google Scholar
Mitteldorf, J. Chaotic population dynamics and the evolution of ageing. Evol Ecol Res 2006; 8: 561–74.Google Scholar
Goldsmith, TC. Aging, evolvability, and the individual benefit requirement; medical implications of aging theory controversies. J Theor Biol 2008; 252: 764–8.Google Scholar
Goldsmith, TC. The case for programmed mammal aging. Russ J Gen Chem 2010; 80: 1434–46.Google Scholar
Goldsmith, TC. Arguments against non-programmed aging theories. Biochemistry (Mosc) 2013; 78: 971–8.Google Scholar
Goldsmith, TC. Modern evolutionary mechanics theories and resolving the programmed/non-programmed aging controversy. Biochemistry (Mosc) 2014; 79: 1049–55.Google Scholar
Goldsmith, TC. Is the evolutionary programmed/non-programmed aging argument moot? Curr Aging Sci 2015; 8: 41–5.CrossRefGoogle ScholarPubMed
Goldsmith, TC. Solving the programmed/non-programmed aging conundrum. Curr Aging Sci 2015; 8: 3440.CrossRefGoogle ScholarPubMed
Mitteldorf, J, Pepper, J. Senescence as an adaptation to limit the spread of disease. J Theor Biol 2009; 260: 186–95.CrossRefGoogle ScholarPubMed
Mitteldorf, J, Martins, AC. Programmed life span in the context of evolvability. Am Nat 2014; 184: 289302.Google Scholar
Kirkwood, TB, Holliday, R. The evolution of ageing and longevity. Proc R Soc Lond B Biol Sci 1979; 205: 531–46.Google Scholar
Kirkwood, TBL, Holliday, R. Ageing as a consequence of natural selection. In Collins, AJ, Bittles, AH, editors. The biology of human ageing, pp. 1–16. Cambridge, UK: Cambridge University Press, 1986.Google Scholar
Hayflick, L. Theories of biological aging. Exp Gerontol 1985; 20: 145–59.Google Scholar
Hayflick, L, Kirkwood, T. How and why we age. Nature 1995; 373: 484.Google Scholar
Hayflick, L. Biological aging is no longer an unsolved problem. Ann N Y Acad Sci 2007; 1100: 113.Google Scholar
Kirkwood, TB, Rose, MR. Evolution of senescence: late survival sacrificed for reproduction. Philos Trans R Soc Lond B Biol Sci 1991; 332: 1524.Google Scholar
Weinert, BT, Timiras, PS. Invited review: theories of aging. J Appl Physiol (1985) 2003; 95: 1706–16.Google Scholar
Austad, SN. Is aging programed? Aging Cell 2004; 3: 249–51.Google Scholar
Kirkwood, TB, Melov, S. On the programmed/non-programmed nature of ageing within the life history. Curr Biol 2011; 21: R701–7.Google Scholar
De Grey, AD. Do we have genes that exist to hasten aging? New data, new arguments, but the answer is still no. Curr Aging Sci 2015; 8: 2433.Google Scholar
Kowald, A, Kirkwood, TB. Can aging be programmed? A critical literature review. Aging Cell 2016; doi: 10.1111/acel.12510.Google Scholar
Kovacs, GG. Molecular pathological classification of neurodegenerative diseases: turning towards precision medicine. Int J Mol Sci 2016; 17: 189.Google Scholar
Jack Jr, CR, Wiste, HJ, Weigand, SD, Knopman, DS, Mielke, MM, Vemuri, P, et al. Different definitions of neurodegeneration produce similar amyloid/neurodegeneration biomarker group findings. Brain 2015; 138: 3747–59.Google Scholar
Mac Donald, CL, Barber, J, Andre, J, Evans, N, Panks, C, Sun, S, et al. 5-Year imaging sequelae of concussive blast injury and relation to early clinical outcome. NeuroImage Clin 2017; 14: 371–8.Google Scholar
Pakkenberg, B, Gundersen, HJ. Neocortical neuron number in humans: effect of sex and age. J Comp Neurol 1997; 384: 312–20.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
Juraska, JM, Lowry, NC. Neuroanatomical changes associated with cognitive aging. Curr Top Behav Neurosci 2012; 10: 137–62.Google Scholar
Stadelmann, C, Mews, I, Srinivasan, A, Deckwerth, TL, Lassmann, H, Brück, W. Expression of cell death‐associated proteins in neuronal apoptosis associated with pontosubicular neuron necrosis. Brain Pathol 2001; 11: 273–81.Google Scholar
Elmore, S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35: 495516.Google Scholar
Serrano-Pozo, A, Frosch, MP, Masliah, E, Hyman, BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 2011; 1: a006189.Google Scholar
Schuff, N, Meyerhoff, DJ, Mueller, S, Chao, L, Sacrey, DT, Laxer, K, et al. N-acetylaspartate as a marker of neuronal injury in neurodegenerative disease. In: Moffett, J, Tieman, SB, Weinberger, DR, Coyle, JT, Namboodiri, AMA (eds) N-Acetylaspartate: a unique neuronal molecule in the central nervous system. New York: Springer; 2006, pp. 241–62.Google Scholar
Herculano-Houzel, S. The human brain in numbers: a linearly scaled-up primate brain. Front Hum Neurosci 2009; 3: 31.Google Scholar
Von Bartheld, CS, Bahney, J, Herculano-Houzel, S. The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting. J Comp Neurol 2016; 524: 3865–95.Google Scholar
West, MJ. New stereological methods for counting neurons. Neurobiol Aging 1993; 14: 275–85.CrossRefGoogle ScholarPubMed
Cahalane, DJ, Charvet, CJ, Finlay, BL. Modeling local and cross-species neuron number variations in the cerebral cortex as arising from a common mechanism. Proc Natl Acad Sci 2014; 111: 17642–7.Google Scholar
Barger, N, Sheley, MF, Schumann, CM. Stereological study of pyramidal neurons in the human superior temporal gyrus from childhood to adulthood. J Comp Neurol 2015; 523: 1054–72.Google Scholar
Altman, J. Are new neurons formed in the brains of adult mammals? Science 1962; 135: 1127–8.Google Scholar
Goldman, SA, Nottebohm, F. Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci 1983; 80: 2390–4.CrossRefGoogle Scholar
Sohur, US, Emsley, JG, Mitchell, BD, Macklis, JD. Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells. Philos Trans R Soc Lond B: Biol Sci 2006; 361: 1477–97.Google Scholar
Drew, MR, Hen, R. Adult hippocampal neurogenesis as target for the treatment of depression. CNS Neurol Disord Drug Targets 2007; 6: 205–18.Google Scholar
Sierra, A, Encinas, JM, Maletic-Savatic, M. Adult human neurogenesis: from microscopy to magnetic resonance imaging. Front Neurosci 2011; 5: 47.Google Scholar
Ugoya, SO, Tu, J. Bench to bedside of neural stem cell in traumatic brain injury. Stem Cells Int 2012; 2012.Google Scholar
Hoekzema, E, Barba-Muller, E, Pozzobon, C, Picado, M, Lucco, F, Garcia-Garcia, D, et al. Pregnancy leads to long-lasting changes in human brain structure. Nat Neurosci 2017; 20: 287–96.Google Scholar
Simerly, RB. Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci 2002; 25: 507–36.Google Scholar
Sisk, CL, Zehr, JL. Pubertal hormones organize the adolescent brain and behavior. Front Neuroendocrinol 2005; 26: 163–74.Google Scholar
Peper, J, Pol, HH, Crone, E, Van Honk, J. Sex steroids and brain structure in pubertal boys and girls: a mini-review of neuroimaging studies. Neuroscience 2011; 191: 2837.Google Scholar
Breitner, JC. Dementia – epidemiological considerations, nomenclature, and a tacit consensus definition. J Geriatr Psychiatry Neurol 2006; 19: 129–36.CrossRefGoogle Scholar
Hay, J, Johnson, VE, Smith, DH, Stewart, W. Chronic traumatic encephalopathy: The neuropathological legacy of traumatic brain injury. Annu Rev Pathol 2016; 11: 2145.Google Scholar
Pinel, P. Nosographie philosophique, ou, La méthode de l’analyse appliquée à la médecine. Paris: Chez JA Brosson, 1818.Google Scholar
Berrios, GE. The history of mental symptoms: descriptive psychopathology since the nineteenth century. Cambridge, UK: Cambridge University Press, 1996.Google Scholar
Kraepelin, E. Psychiatrie – ein Lehrbuch für Studierende und Ärzte, 8. Aufl I–IV. Leipzig: Barth 1909, 1910, 1915.Google Scholar
American Psychological Association. Guidelines for the evaluation of dementia and age-related cognitive change. Am Psychologist 2012; 67: 1.Google Scholar
World Health Organization(WHO). International statistical classification of diseases and related health problems, vol. 10th revision. Geneva: WHO, 2011. Available at http://apps.who.int/classifications/icd10/browse/2016/en.Google Scholar
The European Dementia Consensus Network (EDCON). For whom and for what the definition of severe dementia is useful: an Edcon consensus. J Nutrition Health Aging 2008; 12: 714719.Google Scholar
Wells, CE. Dementia: definition and description. Contemp Neurol Ser 1977; 15: 114.Google Scholar
Feigenson, JS. Definition of dementia. Stroke 1978; 9: 523.Google Scholar
Mesulam, M-M. Dementia: its definition, differential diagnosis, and subtypes. JAMA 1985; 253: 2559–61.Google Scholar
Loo, H, Plas, J. Dementia – a semantic definition. Gerontology 1986; 32 (Suppl 1): 64–6.Google Scholar
Morris, JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993; 43: 2412–14.Google Scholar
Wallin, A. Current definition and classification of dementia diseases. Acta Neurol Scand Suppl 1996; 168: 3944.Google Scholar
Mitchell, AJ, Malladi, S. Screening and case finding tools for the detection of dementia. Part I: evidence-based meta-analysis of multidomain tests. Am J Geriatr Psychiatry 2010; 18: 759–82.Google ScholarPubMed
Walters, GD. Dementia: continuum or distinct entity? Psychol Aging 2010; 25: 534.Google Scholar
Olde Rikkert, MG, Tona, KD, Janssen, L, Burns, A, Lobo, A, Robert, P, et al. Validity, reliability, and feasibility of clinical staging scales in dementia: a systematic review. Am J Alzheimers Dis Other Dementias 2011; 26: 357–65.Google Scholar
Slavin, MJ, Brodaty, H, Sachdev, PS. Challenges of diagnosing dementia in the oldest old population. J Gerontol A Biol Sci Med Sci 2013; 68: 1103–11.Google Scholar
Katzman, R, Aronson, M, Fuld, P, Kawas, C, Brown, T, Morgenstern, H, et al. Development of dementing illnesses in an 80-year-old volunteer cohort. Ann Neurol 1989; 25: 317–24.Google Scholar
Graves, AB, White, E, Koepsell, TD, Reifler, BV, Van Belle, G, Larson, EB, et al. The association between head trauma and Alzheimer’s disease. Am J Epidemiol 1990; 131: 491501.Google Scholar
Williams, D, Annegers, J, Kokmen, E, O’Brien, P, Kurland, L. Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. Neurology 1991; 41: 1554.CrossRefGoogle ScholarPubMed
Mehta, KM, Ott, A, Kalmijn, S, Slooter, AJ, Van Duijn, CM, Hofman, A, et al. Head trauma and risk of dementia and Alzheimer’s disease: the Rotterdam Study. Neurology 1999; 53: 1959–62.Google Scholar
Plassman, BL, Havlik, RJ, Steffens, DC, Helms, MJ, Newman, TN, Drosdick, D, et al. Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias. Neurology 2000; 55: 1158–66.Google Scholar
Starkstein, SE, Jorge, R. Dementia after traumatic brain injury. Int Psychogeriatr 2005; 17 (Suppl 1): S93–107.Google Scholar
Kiraly, MA, Kiraly, SJ. Traumatic brain injury and delayed sequelae: a review – traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia. Sci World J 2007; 7: 1768–76.Google Scholar
Jawaid, A, Rademakers, R, Kass, JS, Kalkonde, Y, Schulz, PE. Traumatic brain injury may increase the risk for frontotemporal dementia through reduced progranulin. Neurodegen Dis 2009; 6: 219–20.Google Scholar
Dams-O’Connor, K, Gibbons, LE, Bowen, JD, McCurry, SM, Larson, EB, Crane, PK. Risk for late-life re-injury, dementia and death among individuals with traumatic brain injury: a population-based study. J Neurol Neurosurg Psychiatry 2013; 84: 177–82.Google Scholar
Smith, DH, Johnson, VE, Stewart, W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol 2013; 9: 211.Google Scholar
Barnes, DE, Kaup, A, Kirby, KA, Byers, AL, Diaz-Arrastia, R, Yaffe, K. Traumatic brain injury and risk of dementia in older veterans. Neurology 2014; 83: 312–19.Google Scholar
Gardner, RC, Burke, JF, Nettiksimmons, J, Kaup, A, Barnes, DE, Yaffe, K. Dementia risk after traumatic brain injury vs nonbrain trauma: the role of age and severity. JAMA Neurol 2014; 71: 1490–7.Google Scholar
Vincent, AS, Roebuck-Spencer, TM, Cernich, A. Cognitive changes and dementia risk after traumatic brain injury: implications for aging military personnel. Alzheimers Dement 2014; 10: S174–87.Google Scholar
Gardner, RC, Yaffe, K. Traumatic brain injury may increase risk of young onset dementia. Ann Neurol 2014; 75: 339341.Google Scholar
Johnson, VE, Stewart, W. Traumatic brain injury: age at injury influences dementia risk after TBI. Nat Rev Neurol 2015; 11: 128–30.Google Scholar
Plassman, BL, Grafman, J. Traumatic brain injury and late-life dementia. Handb Clin Neurol 2015; 128: 711–22.Google Scholar
Crane, PK, Gibbons, LE, Dams-O’Connor, K, Trittschuh, E, Leverenz, JB, Keene, CD, et al. Association of traumatic brain injury with late-life neurodegenerative conditions and neuropathologic findings. JAMA Neurol 2016; 73: 1062–9.Google Scholar
Gilbert, M, Snyder, C, Corcoran, C, Norton, MC, Lyketsos, CG, Tschanz, JT. The association of traumatic brain injury with rate of progression of cognitive and functional impairment in a population-based cohort of Alzheimer’s disease: the Cache County Dementia Progression Study. Int Psychogeriatr 2014; 26: 1593–601.Google Scholar
Sharp, DJ. The association of traumatic brain injury with rate of progression of cognitive and functional impairment in a population-based cohort of Alzheimer’s disease: the Cache County dementia progression study by Gilbert et al. Late effects of traumatic brain injury on dementia progression. Int Psychogeriatr 2014; 26: 1591–2.Google Scholar
Stoner, CR, Orrell, M, Spector, A. Review of positive psychology outcome measures for chronic illness, traumatic brain injury and older adults: adaptability in dementia? Dement Geriatr Cogn Disord 2015; 40: 340–57.Google Scholar
Wang, HK, Lee, YC, Huang, CY, Liliang, PC, Lu, K, Chen, HJ, Li, YC, Tsai, KJ. Traumatic brain injury causes frontotemporal dementia and TDP-43 proteolysis. Neuroscience 2015; 300: 94103.Google Scholar
Gavett, BE, Stern, RA, McKee, AC. Chronic traumatic encephalopathy: a potential late effect of sport-related concussive and subconcussive head trauma. Clin Sports Med 2011; 30: 179–88.Google Scholar
Omalu, B, Bailes, J, Hamilton, RL, Kamboh, MI, Hammers, J, Case, M, et al. Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery 2011; 69: 173–83.Google Scholar
McKee, AC, Stern, RA, Nowinski, CJ, Stein, TD, Alvarez, VE, Daneshvar, DH, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain 2013; 136: 4364.CrossRefGoogle ScholarPubMed
Mez, J, Stern, RA, McKee, AC. Chronic traumatic encephalopathy: where are we and where are we going? Curr Neurol Neurosci Rep 2013; 13: 407.Google Scholar
Stein, TD, Alvarez, VE, McKee, AC. Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel. Alzheimers Res Ther 2014; 6: 4.Google Scholar
Castellani, RJ. Chronic traumatic encephalopathy: a paradigm in search of evidence? Lab Invest 2015; 95: 576–84.Google Scholar
Daneshvar, DH, Goldstein, LE, Kiernan, PT, Stein, TD, McKee, AC. Post-traumatic neurodegeneration and chronic traumatic encephalopathy. Mol Cell Neurosci 2015; 66: 8190.Google Scholar
Faden, AI, Loane, DJ. Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Neurotherapeutics 2015; 12: 143–50.Google Scholar
Zhang, Q-G, Laird, MD, Han, D, Nguyen, K, Scott, E, Dong, Y, et al. Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury. PLoS One 2012; 7: e34504.Google Scholar
Elder, GA, Gama Sosa, MA, De Gasperi, R, Stone, JR, Dickstein, DL, Haghighi, F, et al. Vascular and inflammatory factors in the pathophysiology of blast-induced brain injury. Front Neurol 2015; 6: 48.Google Scholar
Collins-Praino, LE, Corrigan, F. Does neuroinflammation drive the relationship between tau hyperphosphorylation and dementia development following traumatic brain injury? Brain Behav Immun 2017; 60: 369–82.Google Scholar
Kumar, A, Stoica, BA, Loane, DJ, Yang, M, Abulwerdi, G, Khan, N, et al. Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury. J Neuroinflamm 2017; 14: 47.Google Scholar
Lagraoui, M, Sukumar, G, Latoche, JR, Maynard, SK, Dalgard, CL, Schaefer, BC. Salsalate treatment following traumatic brain injury reduces inflammation and promotes a neuroprotective and neurogenic transcriptional response with concomitant functional recovery. Brain Behav Immun 2017; 61: 96109.Google Scholar
Simon, DW, McGeachy, MJ, Bayır, H, Clark, RS, Loane, DJ, Kochanek, PM. The far-reaching scope of neuroinflammation after traumatic brain injury. Nat Rev Neurol 2017; 13: 171–91.Google Scholar
Logsdon, AF, Lucke‐Wold, BP, Turner, RC, Huber, JD, Rosen, CL, Simpkins, JW. Role of microvascular disruption in brain damage from traumatic brain injury. Comp Physiol 2015; 5: 1147–60.Google Scholar
Andrews, AM, Lutton, EM, Merkel, SF, Razmpour, R, Ramirez, SH. Mechanical injury induces brain endothelial-derived microvesicle release: implications for cerebral vascular injury during traumatic brain injury. Front Cell Neurosci 2016; 10.Google Scholar
Toth, P, Szarka, N, Farkas, E, Ezer, E, Czeiter, E, Amrein, K, et al. Traumatic brain injury-induced autoregulatory dysfunction and spreading depression-related neurovascular uncoupling: pathomechanisms, perspectives, and therapeutic implications. Am J Physiol-Heart Circ Physiol 2016; 311: H1118–31.Google Scholar
Salehi, A, Zhang, JH, Obenaus, A. Response of the cerebral vasculature following traumatic brain injury. J Cereb Blood Flow Metab 2017; 37: 23202339. 271678X17701460.Google Scholar
Hay, JR, Johnson, VE, Young, AM, Smith, DH, Stewart, W. Blood–brain barrier disruption is an early event that may persist for many years after traumatic brain injury in humans. J Neuropathol Exp Neurol 2015; 74: 1147–57.Google Scholar
Plog, BA, Dashnaw, ML, Hitomi, E, Peng, W, Liao, Y, Lou, N, et al. Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system. J Neurosci 2015; 35: 518–26.Google Scholar
Nasser, M, Bejjani, F, Raad, M, Abou-El-Hassan, H, Mantash, S, Nokkari, A, et al. Traumatic brain injury and blood–brain barrier cross-talk. CNS Neurol Disord-Drug Targets 2016; 15: 1030–44.Google Scholar
Li, W, Watts, L, Long, J, Zhou, W, Shen, Q, Jiang, Z, et al. Spatiotemporal changes in blood–brain barrier permeability, cerebral blood flow, T2 and diffusion following mild traumatic brain injury. Brain Res 2016; 1646: 5361.Google Scholar
Rodriguez-Rodriguez, A, Egea-Guerrero, JJ, Murillo-Cabezas, F, Carrillo-Vico, A. Oxidative stress in traumatic brain injury. Curr Med Chem 2014; 21: 1201–11.Google Scholar
Amorini, AM, Lazzarino, G, Di Pietro, V, Signoretti, S, Lazzarino, G, Belli, A, et al. Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury. Biochim Biophys Acta 2016; 1862: 679–87.Google Scholar
Besson, VC. Drug targets for traumatic brain injury from poly(ADP-ribose)polymerase pathway modulation. Br J Pharmacol 2009; 157: 695704.Google Scholar
Pu, B, Xue, Y, Wang, Q, Hua, C, Li, X. Dextromethorphan provides neuroprotection via anti-inflammatory and anti-excitotoxicity effects in the cortex following traumatic brain injury. Mol Med Report 2015; 12: 3704–10.Google Scholar
Maneshi, MM, Maki, B, Gnanasambandam, R, Belin, S, Popescu, GK, Sachs, F, et al. Mechanical stress activates NMDA receptors in the absence of agonists. Sci Rep 2017; 7: 39610.Google Scholar
Sommer, JB, Bach, A, Mala, H, Stromgaard, K, Mogensen, J, Pickering, DS. In vitro and in vivo effects of a novel dimeric inhibitor of PSD-95 on excitotoxicity and functional recovery after experimental traumatic brain injury. Eur J Neurosci 2017; 45: 238–48.Google Scholar
Gerson, J, Castillo-Carranza, DL, Sengupta, U, Bodani, R, Prough, DS, Dewitt, DS, et al. Tau oligomers derived from traumatic brain injury cause cognitive impairment and accelerate onset of pathology in Htau mice. J Neurotrauma 2016; 33: 2034–43.Google Scholar
Edwards, G, 3rd, Moreno-Gonzalez, I, Soto, C. Amyloid-beta and tau pathology following repetitive mild traumatic brain injury. Biochem Biophys Res Commun 2017; 483; 8: 1137–42.Google Scholar
Kriegel, J, Papadopoulos, Z, Mckee, AC. Chronic traumatic encephalopathy: is latency in symptom onset explained by tau propagation? Cold Spring Harb Perspect Med 2017: a024059.Google Scholar
Madathil, SK, Saatman, KE. IGF-1/IGF-R signaling in traumatic brain injury: impact on cell survival, neurogenesis, and behavioral outcome. In: Kobeissy FH, editor. Brain neurotrauma: molecular, neuropsychological, and rehabilitation aspects. Boca Raton, FL: CRC Press, 2015, pp. 6178.Google Scholar
Zheng, P, Tong, W. IGF-1: an endogenous link between traumatic brain injury and Alzheimer disease? J Neurosurg Sci 2017; 61: 416–21.Google Scholar
Rothman, MS, Arciniegas, DB, Filley, CM, Wierman, ME. The neuroendocrine effects of traumatic brain injury. J Neuropsychiatry Clin Neurosci 2007; 19: 363–72.Google Scholar
Simpkins, JW, Yang, S-H, Sarkar, SN, Pearce, V. Estrogen actions on mitochondria – physiological and pathological implications. Mol Cell Endocrinol 2008; 290: 51–9.CrossRefGoogle ScholarPubMed
Srinivasan, L, Roberts, B, Bushnik, T, Englander, J, Spain, DA, Steinberg, GK, et al. The impact of hypopituitarism on function and performance in subjects with recent history of traumatic brain injury and aneurysmal subarachnoid haemorrhage. Brain Inj 2009; 23: 639–48.Google Scholar
Wilkinson, CW, Pagulayan, KF, Petrie, EC, Mayer, CL, Colasurdo, EA, Shofer, JB, et al. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury. Front Neurol 2012; 3: 11.Google Scholar
Haghighi, F, Ge, Y, Chen, S, Xin, Y, Umali, MU, De Gasperi, R, et al. Neuronal DNA methylation profiling of blast-related traumatic brain injury. J Neurotrauma 2015; 32: 1200–9.Google Scholar
Wang, X, Seekaew, P, Gao, X, Chen, J. Traumatic brain injury stimulates neural stem cell proliferation via mammalian target of rapamycin signaling pathway activation. eneuro 2016; 3: ENEURO. 0162-16.2016.Google Scholar
Buchman, AS, Yu, L, Boyle, PA, Schneider, JA, De Jager, PL, Bennett, DA. Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. Neurology 2016; 86: 735–41.Google Scholar
Corrigan, F, Arulsamy, A, Teng, J, Collins-Praino, LE. Pumping the brakes: neurotrophic factors for the prevention of cognitive impairment and dementia after traumatic brain injury. J Neurotrauma 2017; 34: 971–86.Google Scholar
Iliff, JJ, Chen, MJ, Plog, BA, Zeppenfeld, DM, Soltero, M, Yang, L, et al. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci 2014; 34: 16180–93.Google Scholar
Simon, MJ, Iliff, JJ. Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease. Biochim Biophys Acta 2016; 1862: 442–51.Google Scholar
Jaarsma, D, Van Der Pluijm, I, De Waard, MC, Haasdijk, ED, Brandt, R, Vermeij, M, et al. Age-related neuronal degeneration: complementary roles of nucleotide excision repair and transcription-coupled repair in preventing neuropathology. PLoS Genet 2011; 7: e1002405.Google Scholar
Wurzelmann, M, Romeika, J, Sun, D. Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury. Neural Regener Res 2017; 12: 7.Google Scholar
Bonilha, L, Jensen, JH, Baker, N, Breedlove, J, Nesland, T, Lin, JJ, et al. The brain connectome as a personalized biomarker of seizure outcomes after temporal lobectomy. Neurology 2015; 84: 1846–53.CrossRefGoogle ScholarPubMed
Bianciardi, M, Toschi, N, Eichner, C, Polimeni, JR, Setsompop, K, Brown, EN, et al. In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI. MAGMA 2016; 29: 451–62.Google Scholar
Folstein, MF, Folstein, SE, Mchugh, PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–98.Google Scholar
Wolf-Klein, GP, Silverstone, FA, Levy, AP, Brod, MS. Screening for Alzheimer’s disease by clock drawing. J Am Geriatr Soc 1989; 37: 730–4.Google Scholar
Nasreddine, ZS, Phillips, NA, Bédirian, V, Charbonneau, S, Whitehead, V, Collin, I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005; 53: 695–9.Google Scholar
Sheehan, B. Assessment scales in dementia. Ther Adv Neurol Disord 2012; 5: 349–58.Google Scholar
Lin, JS, O’Connor, E, Rossom, RC, Perdue, LA, Eckstrom, E. Screening for cognitive impairment in older adults: a systematic review for the US Preventive Services Task Force. Ann Intern Med 2013; 159: 601–12.Google Scholar
Roberts, GW, Allsop, D, Bruton, C. The occult aftermath of boxing. J Neurol Neurosurg Psychiatry 1990; 53: 373–8.CrossRefGoogle ScholarPubMed
Mortimer, J, Van Duijn, C, Chandra, V, Fratiglioni, L, Graves, A, Heyman, A, et al. Head trauma as a risk factor for Alzheimer’s disease: a collaborative re-analysis of case-control studies. Int J Epidemiol 1991; 20: S28–35.Google Scholar
Fleminger, S, Oliver, DL, Lovestone, S, Rabe-Hesketh, S, Giora, A. Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry 2003; 74: 857–62.Google Scholar
Nordstrom, P, Michaelsson, K, Gustafson, Y, Nordstrom, A. Traumatic brain injury and young onset dementia: a nationwide cohort study. Ann Neurol 2014; 75: 374–81.Google Scholar
Alzheimer, A. Uber eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatrie 1907; 64: 146–8.Google Scholar
Stelzmann, RA, Schnitzlein, HN, Murllagh, FR. An English translation of Alzheimer’s 1907 Paper, “Uber eine eigenartige Erlranliung der Hirnrinde”. Clin Anat 1995; 8: 429431.Google Scholar
Alzheimer, A. Über eigenartige Krankheitsfälle des späteren Alters. Z gesamte Neurol Psychiatrie 1911; 4: 356–85.Google Scholar
Alzheimer, A. Ueber den Abbau des Nervengewebes. Allg Z Psychiatrie 1906; 63: 568.Google Scholar
Shanafelt, TD, Boone, S, Tan, L, Dyrbye, LN, Sotile, W, Satele, D, et al. Burnout and satisfaction with work–life balance among US physicians relative to the general US population. Arch Intern Med 2012; 172: 1377–85.Google Scholar
Busis, NA, Shanafelt, TD, Keran, CM, Levin, KH, Schwarz, HB, Molano, JR, et al. Burnout, career satisfaction, and well-being among US neurologists in 2016. Neurology 2017; 88: 797808.Google Scholar
McKhann, G, Drachman, D, Folstein, M, Katzman, R, Price, D, Stadlan, EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS‐ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34: 939.Google Scholar
Mirra, SS, Heyman, A, McKeel, D, Sumi, S, Crain, BJ, Brownlee, L, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD): part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 1991; 41: 479.Google Scholar
Mirra, SS, Hart, MN, Terry, RD. Making the diagnosis of Alzheimer’s disease. A primer for practicing pathologists. Arch Pathol Lab Med 1993; 117: 132–44.Google Scholar
The National Institute on Aging and Reagan Institute Working Group On Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease. Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. Neurobiol Aging 1997; 18: S1S2.Google Scholar
Hyman, BT, Phelps, CH, Beach, TG, Bigio, EH, Cairns, NJ, Carrillo, MC, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement 2012; 8: 113.Google Scholar
McKeel Jr, DW, Price, JL, Miller, JP, Grant, EA, Xiong, C, Berg, L, et al. Neuropathologic criteria for diagnosing Alzheimer disease in persons with pure dementia of Alzheimer type. J Neuropathol Exp Neurol 2004; 63: 1028–37.Google Scholar
Dubois, B, Feldman, HH, Jacova, C, Dekosky, ST, Barberger-Gateau, P, Cummings, J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS–ADRDA criteria. Lancet Neurol 2007; 6: 734–46.Google Scholar
Dubois, B, Feldman, HH, Jacova, C, Hampel, H, Molinuevo, JL, Blennow, K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 2014; 13: 614–29.Google Scholar
Braak, H, Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82: 239–59.Google Scholar
Dubois, B, Feldman, HH, Jacova, C, Cummings, JL, Dekosky, ST, Barberger-Gateau, P, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 2010; 9: 1118–27.Google Scholar
Oksengard, A, Cavallin, L, Axelsson, R, Andersson, C, Nägga, K, Winblad, B, et al. Lack of accuracy for the proposed ‘Dubois criteria’ in Alzheimer’s disease: a validation study from the Swedish brain power initiative. Dement Geriatr Cogn Disord 2010; 30: 374–80.Google Scholar
Wirth, M, Madison, CM, Rabinovici, GD, Oh, H, Landau, SM, Jagust, WJ. Alzheimer’s disease neurodegenerative biomarkers are associated with decreased cognitive function but not β-amyloid in cognitively normal older individuals. J Neurosci 2013; 33: 5553–63.Google Scholar
Blessed, G, Tomlinson, BE, Roth, M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968; 114: 797811.Google Scholar
Katzman, R. Editorial: the prevalence and malignancy of Alzheimer disease. A major killer. Arch Neurol 1976; 33: 217–18.Google Scholar
Mendez, MF. Early-onset Alzheimer’s disease: nonamnestic subtypes and type 2 AD. Arch Med Res 2012; 43: 677–85.Google Scholar
Glenner, G, Harbaugh, J, Ohms, J, Harada, M, Cuatrecasas, P. An amyloid protein: the amino-terminal variable fragment of an immunoglobulin light chain. Biochem Biophys Res Commun 1970; 41: 1287–9.Google Scholar
Glenner, GG, Wong, CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120: 885–90.Google Scholar
Hardy, J, Allsop, D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 1991; 12: 383–8.Google Scholar
Selkoe, DJ. The molecular pathology of Alzheimer’s disease. Neuron 1991; 6: 487–98.Google Scholar
Hardy, JA, Higgins, GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992; 256: 184–5.Google Scholar
Cárdenas-Aguayo, MDC, Silva-Lucero, MDC, Cortes-Ortiz, M, Jiménez-Ramos, B, Gómez-Virgilio, L, Ramírez-Rodríguez, G, et al. Physiological role of amyloid beta in neural cells: the cellular trophic activity. InTech 2014; 124.Google Scholar
Morley, JE, Farr, SA, Banks, WA, Johnson, SN, Yamada, KA, Xu, L. A physiological role for amyloid-β protein: enhancement of learning and memory. J Alzheimers Dis 2010; 19: 441–9.Google Scholar
Dawkins, E, Small, DH. Insights into the physiological function of the beta-amyloid precursor protein: beyond Alzheimer’s disease. J Neurochem 2014; 129: 756–69.Google Scholar
Rajmohan, R, Reddy, PH. Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. J Alzheimers Dis 2017; 57: 975–99.Google Scholar
Greenberg, SM, William Rebeck, G, Vonsattel, JPG, Gomez‐Isla, T, Hyman, BT. Apolipoprotein E ϵ4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol 1995; 38: 254–9.Google Scholar
Terry, RD, Masliah, E, Hansen, LA. The neuropathology of Alzheimer disease and the structural basis of its cognitive alterations. Alzheimer Dis 1999; 2: 187206.Google Scholar
Mega, MS, Dinov, ID, Porter, V, Chow, G, Reback, E, Davoodi, P, et al. Metabolic patterns associated with the clinical response to galantamine therapy: a fludeoxyglucose F 18 positron emission tomographic study. Arch Neurol 2005; 62: 721–8.Google Scholar
Aizenstein, HJ, Nebes, RD, Saxton, JA, Price, JC, Mathis, CA, Tsopelas, ND, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 2008; 65: 1509–17.Google Scholar
Jack Jr, CR, Lowe, VJ, Senjem, ML, Weigand, SD, Kemp, BJ, Shiung, MM, et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain 2008; 131: 665–80.Google Scholar
Sperling, RA, Laviolette, PS, O’Keefe, K, O’Brien, J, Rentz, DM, Pihlajamaki, M, et al. Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron 2009; 63: 178–88.Google Scholar
Forsberg, A, Almkvist, O, Engler, H, Wall, A, Langstrom, B, Nordberg, A. High PIB retention in Alzheimer’s disease is an early event with complex relationship with CSF biomarkers and functional parameters. Curr Alzheimer Res 2010; 7: 5666.Google Scholar
Hyman, BT. Amyloid-dependent and amyloid-independent stages of Alzheimer disease. Arch Neurol 2011; 68: 1062–4.Google Scholar
Morris, GP, Clark, IA, Vissel, B. Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer’s disease. Acta Neuropathol Commun 2014; 2: 135.Google Scholar
Karran, E, De Strooper, B. The amyloid cascade hypothesis: are we poised for success or failure? J Neurochem 2016; 139 (Suppl 2): 237–52.Google Scholar
Sakono, M, Zako, T. Amyloid oligomers: formation and toxicity of Ab oligomers. FEBS 2010; 277: 13481358.Google Scholar
Gadad, BS, Britton, GB, Rao, K. Targeting oligomers in neurodegenerative disorders: lessons from α-synuclein, tau, and amyloid-β peptide. J Alzheimers Dis 2011; 24: 223–32.Google Scholar
Sell, GL, Schaffer, TB, Margolis, SS. Reducing expression of synapse-restricting protein Ephexin5 ameliorates Alzheimer’s-like impairment in mice. J Clin Invest 2017; 127: 1646–50.Google Scholar
Haass, C, Selkoe, DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 2007; 8: 101–12.Google Scholar
Maruyama, M, Shimada, H, Suhara, T, Shinotoh, H, Ji, B, Maeda, J, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 2013; 79: 1094–108.Google Scholar
Lloret, A, Fuchsberger, T, Giraldo, E, Vina, J. Molecular mechanisms linking amyloid beta toxicity and Tau hyperphosphorylation in Alzheimer’s disease. Free Radic Biol Med 2015; 83: 186–91.Google Scholar
Selkoe, DJ, Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016; 8: 595608.Google Scholar
Taipa, R, Sousa, AL, Melo Pires, M, Sousa, N. Does the interplay between aging and neuroinflammation modulate Alzheimer’s disease clinical phenotypes? A clinico-pathological perspective. J Alzheimers Dis 2016; 53: 403–17.Google Scholar
Sarazin, M, Berr, C, De Rotrou, J, Fabrigoule, C, Pasquier, F, Legrain, S, et al. Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study. Neurology 2007; 69: 1859–67.Google Scholar
Stones, MJ. Aging and semantic memory: structural age differences. Exp Aging Res 1978; 4: 125–32.Google Scholar
Barbeau, E, Didic, M, Tramoni, E, Felician, O, Joubert, S, Sontheimer, A, et al. Evaluation of visual recognition memory in MCI patients. Neurology 2004; 62: 1317–22.Google Scholar
Ribeiro, F, Guerreiro, M, De Mendonça, A. Verbal learning and memory deficits in mild cognitive impairment. J Clin Exp Neuropsychol 2007; 29: 187–97.Google Scholar
Kessels, RP, Meulenbroek, O, Fernández, G, Olde Rikkert, MG. Spatial working memory in aging and mild cognitive impairment: effects of task load and contextual cueing. Aging Neuropsychol Cogn 2010; 17: 556–74.Google Scholar
Fjell, AM, McEvoy, L, Holland, D, Dale, AM, Walhovd, KB, Alzheimer’s Disease Neuroimaging Initiative. What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Prog Neurobiol 2014; 117: 2040.Google Scholar
Armstrong, RA. On the ‘classification’ of neurodegenerative disorders: discrete entities, overlap or continuum? Folia Neuropathol 2012; 50: 201–18.Google Scholar
Jack, CR, Bennett, DA, Blennow, K, Carrillo, MC, Feldman, HH, Frisoni, GB, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016; 87: 539547.Google Scholar
Prescott, JW, Guidon, A, Doraiswamy, PM, Roy Choudhury, K, Liu, C, Petrella, JR. The Alzheimer structural connectome: changes in cortical network topology with increased amyloid plaque burden. Radiology 2014; 273: 175–84.Google Scholar
Van Den Heuvel, MP, De Reus, MA. Chasing the dreams of early connectionists. ACS Chem Neurosci 2014; 5: 491–3.Google Scholar
Jack, CR, Albert, MS, Knopman, DS, McKhann, GM, Sperling, RA, Carrillo, MC, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 257–62.Google Scholar
Mckhann, GM, Knopman, DS, Chertkow, H, Hyman, BT, Jack, CR, Kawas, CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 263–9.Google Scholar
Visser, PJ, Vos, S, Van Rossum, I, Scheltens, P. Comparison of International Working Group criteria and National Institute on Aging–Alzheimer’s Association criteria for Alzheimer’s disease. Alzheimers Dement 2012; 8: 560–3.Google Scholar
Albert, MS, Dekosky, ST, Dickson, D, Dubois, B, Feldman, HH, Fox, NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 270–9.Google Scholar
Sperling, RA, Aisen, PS, Beckett, LA, Bennett, DA, Craft, S, Fagan, AF et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer Demen 2011; 7: 280292.Google Scholar
Chen, M, Maleski, JJ, Sawmiller, DR. Scientific truth or false hope? Understanding Alzheimer’s disease from an aging perspective. J Alzheimers Dis 2011; 24: 310.Google Scholar
Whitehouse, PJ, George, DR, D’alton, S. Describing the dying days of “Alzheimer’s disease.” J Alzheimers Dis 2011; 24: 1113.Google Scholar
Ferrer, I. Defining Alzheimer as a common age-related neurodegenerative process not inevitably leading to dementia. Prog Neurobiol 2012; 97: 3851.Google Scholar
Neill, D. Should Alzheimer’s disease be equated with human brain ageing? A maladaptive interaction between brain evolution and senescence. Ageing Res Rev 2012; 11: 104–22.Google Scholar
Burns, JM, Bennett, DA. Parsing the heterogeneity of mild cognitive impairment: lumpers and splitters. Neurology 2015; 85: 1646–7.Google Scholar
Mullane, K, Williams, M. Alzheimer’s therapeutics: continued clinical failures question the validity of the amyloid hypothesis – but what lies beyond? Biochem Pharmacol 2013; 85: 289305.Google Scholar
Drachman, DA. The amyloid hypothesis, time to move on: amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimers Dement 2014; 10: 372–80.Google Scholar
Lambert, JC, Ibrahim-Verbaas, CA, Harold, D, Naj, AC, Sims, R, Bellenguez, C, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 2013; 45: 1452–8.Google Scholar
Karch, CM, Goate, AM. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry 2015; 77: 4351.Google Scholar
Mormino, EC, Sperling, RA, Holmes, AJ, Buckner, RL, De Jager, PL, Smoller, JW, et al. Polygenic risk of Alzheimer disease is associated with early- and late-life processes. Neurology 2016; 87: 481–8.Google Scholar
Morgan, K. The three new pathways leading to Alzheimer’s disease. Neuropathol Appl Neurobiol 2011; 37: 353–7.Google Scholar
International Genomics of Alzheimer’s Disease Consortium. Convergent genetic and expression data implicate immunity in Alzheimer’s disease. Alzheimers Dement 2015; 11: 658–71.Google Scholar
Van Der Zee, J, Sleegers, K, Van Broeckhoven, C. Invited article: the Alzheimer disease–frontotemporal lobar degeneration spectrum. Neurology 2008; 71: 1191–7.Google Scholar
Duker, AP, Espay, AJ, Wszolek, ZK, Rademakers, R, Dickson, DW, Kelley, BJ. Atypical motor and behavioral presentations of Alzheimer disease: a case-based approach. Neurologist 2012; 18: 266–72.Google Scholar
Dohler, F, Sepulveda-Falla, D, Krasemann, S, Altmeppen, H, Schluter, H, Hildebrand, D, et al. High molecular mass assemblies of amyloid-beta oligomers bind prion protein in patients with Alzheimer’s disease. Brain 2014; 137: 873–86.Google Scholar
Josephs, KA, Murray, ME, Whitwell, JL, Parisi, JE, Petrucelli, L, Jack, CR, et al. Staging TDP-43 pathology in Alzheimer’s disease. Acta Neuropathol 2014; 127: 441–50.Google Scholar
Bettcher, BM, Kramer, JH. Longitudinal inflammation, cognitive decline, and Alzheimer’s disease: a mini-review. Clin Pharmacol Ther 2014; 96: 464–9.Google Scholar
Kauwe, JS, Bailey, MH, Ridge, PG, Perry, R, Wadsworth, ME, Hoyt, KL, et al. Genome-wide association study of CSF levels of 59 Alzheimer’s disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation. PLoS Genet 2014; 10: e1004758.Google Scholar
Nelson, L, Gard, P, Tabet, N. Hypertension and inflammation in Alzheimer’s disease: close partners in disease development and progression! J Alzheimers Dis 2014; 41: 331–43.Google Scholar
Steen, E, Terry, BM, Rivera, EJ, Cannon, JL, Neely, TR, Tavares, R, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease – is this type 3 diabetes? J Alzheimers Dis 2005; 7: 6380.Google Scholar
Candeias, E, Duarte, AI, Carvalho, C, Correia, SC, Cardoso, S, Santos, RX, et al. The impairment of insulin signaling in Alzheimer’s disease. IUBMB Life 2012; 64: 951–7.Google Scholar
Ferreira, ST, Clarke, JR, Bomfim, TR, De Felice, FG. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement 2014; 10: S76–83.Google Scholar
Honjo, K, Black, SE, Verhoeff, NP. Alzheimer’s disease, cerebrovascular disease, and the beta-amyloid cascade. Can J Neurol Sci 2012; 39: 712–28.Google Scholar
Kling, MA, Trojanowski, JQ, Wolk, DA, Lee, VM, Arnold, SE. Vascular disease and dementias: paradigm shifts to drive research in new directions. Alzheimers Dement 2013; 9: 7692.Google Scholar
Toledo, JB, Arnold, SE, Raible, K, Brettschneider, J, Xie, SX, Grossman, M, et al. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 2013; 136: 2697–706.Google Scholar
Bangen, KJ, Nation, DA, Delano-Wood, L, Weissberger, GH, Hansen, LA, Galasko, DR, et al. Aggregate effects of vascular risk factors on cerebrovascular changes in autopsy-confirmed Alzheimer’s disease. Alzheimers Dement 2015; 11: 394–403. e1.Google Scholar
Lee, CW, Shih, YH, Kuo, YM. Cerebrovascular pathology and amyloid plaque formation in Alzheimer’s disease. Curr Alzheimer Res 2014; 11: 410.Google Scholar
Tosto, G,Bird, TD, Bennet, DA, Boeve, BF, Brickman, AM, Cruchaga, C, et al. The role of cardiovascular risk factors and stroke in familial Alzheimer disease. JAMA Neurology 2016; 73: 1231–7.Google Scholar
Castellani, RJ. Chronic traumatic encephalopathy: a paradigm in search of evidence? Lab Invest 2015; 95: 576–84.Google Scholar
McKee, AC, Cairns, NJ, Dickson, DW, Folkerth, RD, Keene, CD, Litvan, I, et al. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 2016; 131: 7586.Google Scholar
Parker, HL. Traumatic encephalopathy (‘punch drunk’) of professional pugilists. J Neurol Psychopathol 1934; 1: 20–8.Google Scholar
Figueira, I, Fernandes, A, Mladenovic Djordjevic, A, Lopez-Contreras, A, Henriques, CM, Selman, C, et al. Interventions for age-related diseases: shifting the paradigm. Mech Ageing Dev 2016; 160: 6992.Google Scholar
Guskiewicz, KM, Marshall, SW, Bailes, J, McCrea, M, Cantu, RC, Randolph, C, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery 2005; 57: 719–26.Google Scholar
Guskiewicz, KM, Marshall, SW, Bailes, J, McCrea, M, Harding, HP, Jr., Matthews, A, et al. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc 2007; 39: 903–9.Google Scholar
Lovell, MR, Iverson, GL, Collins, MW, McKeag, D, Maroon, JC. Does loss of consciousness predict neuropsychological decrements after concussion? LWW; 1999; 9: 193–8.Google Scholar
Kelly, JP. Loss of consciousness: pathophysiology and implications in grading and safe return to play. J Athl Train 2001; 36: 249–52.Google Scholar
Broglio, SP, Cantu, RC, Gioia, GA, Guskiewicz, KM, Kutcher, J, Palm, M, et al. National Athletic Trainers’ Association position statement: management of sport concussion. J Athl Train 2014; 49: 245–65.Google Scholar
Scorza, KA, Raleigh, MF, O’Connor, FG. Current concepts in concussion: evaluation and management. Am Fam Physician 2012; 85: 123–32.Google Scholar
Talavage, TM, Nauman, EA, Breedlove, EL, Yoruk, U, Dye, AE, Morigaki, KE, et al. Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion. J Neurotrauma 2014; 31: 327–38.Google Scholar
Longhi, L, Saatman, KE, Fujimoto, S, Raghupathi, R, Meaney, DF, Davis, J, et al. Temporal window of vulnerability to repetitive experimental concussive brain injury. Neurosurgery 2005; 56: 364–74.Google Scholar
Tavazzi, B, Lazzarino, G, Amorini, AM, Vagnozzi, R, Signoretti, S, Di Pietro, V. Temporal window of metabolic brain vulnerability to concussion: a pilot 1H-MRS study in concussed athletes-part III. Neurosurgery 2008; 2008: 1286–95.Google Scholar
Maroon, JC, Bailes, J, Collins, M, Lovell, M, Mathyssek, C, Andrikopoulos, J, et al. Age of first exposure to football and later-life cognitive impairment in former NFL players. Neurology 2015; 85: 1007–10.Google Scholar
Stamm, JM, Koerte, IK, Muehlmann, M, Pasternak, O, Bourlas, AP, Baugh, CM, et al. Age at first exposure to football is associated with altered corpus callosum white matter microstructure in former professional football players. J Neurotrauma 2015; 32: 17681776.Google Scholar
Gysland, SM, Mihalik, JP, Register-Mihalik, JK, Trulock, SC, Shields, EW, Guskiewicz, KM. The relationship between subconcussive impacts and concussion history on clinical measures of neurologic function in collegiate football players. Ann Biomed Eng 2012; 40: 1422.Google Scholar
Kerr, ZY, Littleton, AC, Cox, LM, Defreese, JD, Varangis, E, Lynall, RC, et al. Estimating contact exposure in football using the head impact exposure estimate. J Neurotrauma 2015; 32: 1083–9.Google Scholar
Greenwald, RM, Gwin, JT, Chu, JJ, Crisco, JJ. Head impact severity measures for evaluating mild traumatic brain injury risk exposure. Neurosurgery 2008; 62: 789–98; discussion 798.Google Scholar
Montenigro, PH, Alosco, ML, Martin, BM, Daneshvar, DH, Mez, J, Chaisson, CE, et al. Cumulative head impact exposure predicts later-life depression, apathy, executive dysfunction, and cognitive impairment in former high school and college football players. J Neurotrauma 2017; 34: 328–40.Google Scholar
Martland, HS. Punch drunk. JAMA 1928; 91: 1103–7.Google Scholar
Critchley, M. Punch-drunk syndromes: the chronic traumatic encephalopathy of boxers. In: Hommage à Clovis Vincent. Paris: Maloine; 1949, pp. 131–41.Google Scholar
Brandenburg, W, Hallervorden, J. [Dementia pugilistica with anatomical findings.] Virchows Arch Pathol Anat Physiol Klin Med 1954; 325: 680709.Google Scholar
Corsellis, JA, Bruton, CJ, Freeman-Browne, D. The aftermath of boxing. Psychol Med 1973; 3: 270303.Google Scholar
Hof, P, Knabe, R, Bovier, P, Bouras, C. Neuropathological observations in a case of autism presenting with self-injury behavior. Acta Neuropathol 1991; 82: 321–6.Google Scholar
Geddes, J, Vowles, G, Robinson, S, Sutcliffe, J. Neurofibrillary tangles, but not Alzheimer‐type pathology, in a young boxer. Neuropathol Appl Neurobiol 1996; 22: 1216.Google Scholar
Geddes, JF, Vowles, GH, Nicoll, JA, Revesz, T. Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol 1999; 98: 171–8.Google Scholar
Maroon, JC, Winkelman, R, Bost, J, Amos, A, Mathyssek, C, Miele, V. Chronic traumatic encephalopathy in contact sports: a systematic review of all reported pathological cases. PLoS One 2015; 10: e0117338.Google Scholar
Mez, J, Solomon, TM, Daneshvar, DH, Stein, TD, McKee, AC. Pathologically confirmed chronic traumatic encephalopathy in a 25-year-old former college football player. JAMA Neurol 2016; 73: 353–5.Google Scholar
Victoroff, J. Traumatic encephalopathy: review and provisional research diagnostic criteria. NeuroRehabilitation 2013; 32: 211–24.Google Scholar
Alosco, ML, Mez, J, Kowall, NW, Stein, TD, Goldstein, LE, Cantu, RC, et al. Cognitive reserve as a modifier of clinical expression in chronic traumatic encephalopathy: a preliminary examination. J Neuropsychiatry Clin Neurosci 2016; appi. neuropsych. 16030043.Google Scholar
Mez, J, Daneshvar, DH, Kiernan, PT, Abdolmohammadi, B, Alvarez, VE, Huber, BR, et al. Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football. JAMA 2017; 318(4): 360–70.Google Scholar
Puvenna, V, Engeler, M, Banjara, M, Brennan, C, Schreiber, P, Dadas, A, et al. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy. Brain Res 2016; 1630: 225–40.Google Scholar
Bieniek, KF, Ross, OA, Cormier, KA, Walton, RL, Soto-Ortolaza, A, Johnston, AE, et al. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank. Acta Neuropathol 2015; 130: 877–89.Google Scholar
Castellani, RJ, Perry, G, Iverson, GL. Chronic effects of mild neurotrauma: putting the cart before the horse? J Neuropathol Exp Neurol 2015; 74: 493–9.Google Scholar
Stein, TD, Montenigro, PH, Alvarez, VE, Xia, W, Crary, JF, Tripodis, Y, et al. Beta-amyloid deposition in chronic traumatic encephalopathy Acta Neuropathol 2015; 130: 2134.Google Scholar
Cherry, JD, Tripodis, Y, Alvarez, VE, Huber, B, Kiernan, PT, Daneshvar, DH, et al. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy. Acta Neuropathol Commun 2016; 4: 112.Google Scholar
Uryu, K, Chen, X-H, Martinez, D, Browne, KD, Johnson, VE, Graham, DI, et al. Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp Neurol 2007; 208: 185–92.Google Scholar
Brody, DL, Benetatos, J, Bennett, RE, Klemenhagen, KC, Mac Donald, CL. The pathophysiology of repetitive concussive traumatic brain injury in experimental models; new developments and open questions. Mol Cell Neurosci 2015; 66: 91–8.Google Scholar
Johnson, VE, Stewart, W, Trojanowski, JQ, Smith, DH. Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans. Acta Neuropathol 2011; 122: 715–26.Google Scholar
Johnson, VE, Stewart, JE, Begbie, FD, Trojanowski, JQ, Smith, DH, Stewart, W. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain 2013; 136: 2842.Google Scholar
Roberts, G, Gentleman, S, Lynch, A, Graham, D. βA4 amyloid protein deposition in brain after head trauma. Lancet 1991; 338: 1422–3.Google Scholar
Huber, A, Gabbert, K, Kelemen, J, Cervos-Navarro, J. Density of amyloid plaques in brains after head trauma. J Neurotrauma 1993; 10: S180.Google Scholar
Roberts, G, Gentleman, S, Lynch, A, Murray, L, Landon, M, Graham, D. Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1994; 57: 419–25.Google Scholar
Ikonomovic, MD, Uryu, K, Abrahamson, EE, Ciallella, JR, Trojanowski, JQ, Lee, VM, et al. Alzheimer’s pathology in human temporal cortex surgically excised after severe brain injury. Exp Neurol 2004; 190: 192203.Google Scholar
McKee, AC, Robinson, ME. Military-related traumatic brain injury and neurodegeneration. Alzheimers Dement 2014; 10: S242–53.Google Scholar
Johnson, VE, Stewart, W, Smith, DH. Widespread tau and amyloid‐beta pathology many years after a single traumatic brain injury in humans. Brain Pathol 2012; 22: 142–9.Google Scholar
Arai, T, Hasegawa, M, Akiyama, H, Ikeda, K, Nonaka, T, Mori, H, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 2006; 351: 602–11.Google Scholar
Neumann, M, Sampathu, DM, Kwong, LK, Truax, AC, Micsenyi, MC, Chou, TT, Bruce, J, Schuck, T, Grossman, M, Clark, CM, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314(5796): 130–3.Google Scholar
Mackenzie, IR, Rademakers, R. The role of TDP-43 in amyotrophic lateral sclerosis and frontotemporal dementia. Curr Opin Neurol 2008; 21: 693.Google Scholar
Amador-Ortiz, C, Lin, WL, Ahmed, Z, Personett, D, Davies, P, Duara, R, et al. TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 2007; 61: 435–45.Google Scholar
Higashi, S, Iseki, E, Yamamoto, R, Minegishi, M, Hino, H, Fujisawa, K, et al. Concurrence of TDP-43, tau and alpha-synuclein pathology in brains of Alzheimer’s disease and dementia with Lewy bodies. Brain Res 2007; 1184: 284–94.Google Scholar
Schwab, C, Arai, T, Hasegawa, M, Yu, S, Mcgeer, PL. Colocalization of transactivation-responsive DNA-binding protein 43 and huntingtin in inclusions of Huntington disease. J Neuropathol Exp Neurol 2008; 67: 1159–65.Google Scholar
Wegorzewska, I, Bell, S, Cairns, NJ, Miller, TM, Baloh, RH. TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci 2009; 106: 18809–14.Google Scholar
Lagier-Tourenne, C, Cleveland, DW. Rethinking ALS: the FUS about TDP-43. Cell 2009; 136: 1001–4.Google Scholar
Ling, S-C, Albuquerque, CP, Han, JS, Lagier-Tourenne, C, Tokunaga, S, Zhou, H, et al. ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS. Proc Natl Acad Sci 2010; 107: 13318–23.Google Scholar
McKee, AC, Gavett, BE, Stern, RA, Nowinski, CJ, Cantu, RC, Kowall, NW, et al. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol 2010; 69: 918–29.CrossRefGoogle ScholarPubMed
Goodin, DS, Ebers, GC, Johnson, KP, Rodriguez, M, Sibley, WA, Wolinsky, JS. The relationship of MS to physical trauma and psychological stress: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 1999; 52: 1737–45.Google Scholar
Mendel, K. Tabes und multiple Sklerose in ihren Beziehungen zum Trauma. Neurol Ctrbl 1897; 16: 140–1.Google Scholar
Dana, CL. Multiple sclerosis and the methods of ecology. Res Publ Assoc Nerv Ment Dis 1922; 2: 43–8.Google Scholar
McAlpine, D, Compston, N. Some aspects of the natural history of disseminated sclerosis. Q J Med 1952; 21: 135–67.Google Scholar
Warren, SA, Olivo SA, Contreras JF, Turpin KVL, Gross DP, Carroll LJ, Warren KG. Traumatic injury and multiple sclerosis: a systematic review and meta-analysis. Can J Neurol Sci 2013; 40: 168–76.Google Scholar
Goldacre, MJ, Abisgold JD, Yeates DG, Seagroatt V. Risk of multiple sclerosis after head injury: record linkage study. J Neurol Neurosurg Psychiatry 2006; 77: 351–3.Google Scholar
Pfleger, CC, Koch-Henriksen N, Stenager E, Flachs EM, Johansen C. Head injury is not a risk factor for multiple sclerosis: a prospective cohort study. Mult Scler 2009; 15: 294–8.Google Scholar
Kang, J-H, Lin H-C. Increased risk of multiple sclerosis after traumatic brain injury: a nationwide population-based study. J Neurotrauma 2012; 29: 90–5.Google Scholar
Lunny, CA, Fraser SN, Knopp-Sihota JA. Physical trauma and risk of multiple sclerosis: a systematic review and meta-analysis of observational studies. J Neurol Sci 2014; 336: 13–23.Google Scholar
Siva, A, Radhakrishnan K, Kurland LT, O'Brien PC, Swanson JW, Rodriguez M. Trauma and multiple sclerosis: a population-based cohort study from Olmsted County, Minnesota. Neurology 1993; 43: 1878–82.Google Scholar
Montgomery, M, Hiyoshi A, Burkill S, Alfredsson L, Shahram Bahmanyar S, Tomas Olsson T. Concussion in adolescence and risk of multiple sclerosis. Ann Neurol 2017; 82: 554–61.Google Scholar
Lafrenaye, AD, Todani M, Walker SA, Povlishock JT. Microglia processes associate with diffusely injured axons following mild traumatic brain injury in the micro pig. J Neuroinflamm 2015; 12: 186.Google Scholar
Constantine, G, Buliga M, Mi Q, Constantine F, Abboud A, Zamora R, et al. Dynamic profiling: modeling the dynamics of inflammation and predicting outcomes in traumatic brain injury patients. Front Pharmacol 2016; 7: 383.Google Scholar
Corrigan, F, Mander KA, Leonard AV, Vink R. Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation. J Neuroinflamm 2016; 13: 264.Google Scholar
Naghibi, T, Mohajeri M, Dobakhti F. Inflammation and outcome in traumatic brain injury: does gender effect on survival and prognosis? J Clin Diagn Res 2017; 11: PC06–9.Google Scholar
Mashkouri, S, Crowley MG, Liska MG, Corey S, Borlongan CV. Utilizing pharmacotherapy and mesenchymal stem cell therapy to reduce inflammation following traumatic brain injury. Neural Regen Res 2016; 11: 1379–84.Google Scholar
Chen, X, Wu S, Chen C, Xie B, Fang Z, Hu W, et al. Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury. J Neuroinflamm 2017; 14: 143.Google Scholar
Lagraoui, M, Sukumar G, Latoche JR, Maynard SK, Dalgard CL, Schaefer BC. Salsalate treatment following traumatic brain injury reduces inflammation and promotes a neuroprotective and neurogenic transcriptional response with concomitant functional recovery. Brain Behav Immun 2017; 61: 96–109.Google Scholar
Walker, AE, Caveness, WF, Critchley, M. The late effects of head injury. Springfield, IL: CC Thomas, 1969.Google Scholar
Suddath, RL, Christison, GW, Torrey, EF, Casanova, MF, Weinberger, DR. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med 1990; 322: 789–94.Google Scholar
Rand Health. 36-Item Short Form Survey Instrument (SF-36). 2017. Available from: www.rand.org/health/surveys_tools/mos/36-item-short-form/survey-instrument.html.Google Scholar
Diener, E, Emmons, RA, Larsen, RJ, Griffin, S. The Satisfaction With Life Scale. J Pers Assess 1985; 49: 71–5.Google Scholar
King, N, Crawford, S, Wenden, F, Moss, N, Wade, D. The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability. J Neurol 1995; 242: 587–92.Google Scholar
Holleran, L, Kim, JH, Gangolli, M, Stein, T, Alvarez, V, Mckee, A, et al. Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy. Acta Neuropathol 2017; 133: 367–80.Google Scholar
Castillo-Carranza, DL, Guerrero-Muñoz, MJ, Sengupta, U, Hernandez, C, Barrett, AD, Dineley, K, et al. Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer’s disease mouse model. J Neurosci 2015; 35: 4857–68.Google Scholar
Devos, SL, Miller, RL, Schoch, KM, Holmes, BB, Kebodeaux, CS, Wegener, AJ, et al. Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy. Sci Transl Med 2017; 9: eaag0481.Google Scholar
National Institutes of Health. Designer compound may untangle damage leading to some dementias. 2017. Available from: www.nih.gov/news-events/news-releases/designer-compound-may-untangle-damage-leading-some-dementias.Google Scholar
Garrod, AE. The Croonian lectures on inborn errors of metabolism. Delivered before the Royal College of Physicians on June 18th, 23rd, 25th, and 30th. Lancet 1908; 172(4427): 17; 172(4428): 7379; 172(4429): 142148; 172(4430): 214230.Google Scholar
Garrod, AE, Harris, H. Inborn errors of metabolism. London: Oxford University Press, 1909.Google Scholar
Scriver, CR. Garrod’s Croonian lectures (1908) and the charter ‘Inborn Errors of Metabolism’: albinism, alkaptonuria, cystinuria, and pentosuria at age 100 in 2008. J Inherit Metab Dis 2008; 31: 580–98.Google Scholar