The DOI matches its Crossref record; 205 of the 205 references it cites were found in a registry or an index; 1 of the 218 sources its claims cite were checked for support.
The neuropathology of sport
Open accessAbstract
The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable. Physical activity reduces the risk for cardiovascular disease, type 2 diabetes, hypertension, obesity, and stroke, and produces beneficial effects on cholesterol levels, antioxidant systems, inflammation, and vascular function. Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration. Nonetheless, the play of sports is associated with risks, including a risk for mild TBI (mTBI) and, rarely, catastrophic traumatic injury and death. There is also growing awareness that repetitive mTBIs, such as concussion and subconcussion, can occasionally produce persistent cognitive, behavioral, and psychiatric problems as well as lead to the development of a neurodegeneration, chronic traumatic encephalopathy (CTE). In this review, we summarize the beneficial aspects of sports participation on psychological, emotional, physical and cognitive health, and specifically analyze some of the less common adverse neuropathological outcomes, including concussion, second-impact syndrome, juvenile head trauma syndrome, catastrophic sudden death, and CTE. CTE is a latent neurodegeneration clinically associated with behavioral changes, executive dysfunction and cognitive impairments, and pathologically characterized by frontal and temporal lobe atrophy, neuronal and axonal loss, and abnormal deposits of paired helical filament (PHF)-tau and 43 kDa TAR deoxyribonucleic acid (DNA)-binding protein (TDP-43). CTE often occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including motor neuron disease (CTE-MND). Although the incidence and prevalence of CTE are not known, CTE has been reported most frequently in American football players and boxers. Other sports associated with CTE include ice hockey, professional wrestling, soccer, rugby, and baseball.
Overview
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Written from the paper’s full text.
TL;DR
This review summarizes both the health benefits of exercise and sports participation and the adverse neuropathological outcomes, especially concussion and chronic traumatic encephalopathy (CTE). It reports that repetitive mild TBI in sport can produce persistent symptoms and, in some athletes, CTE, while emphasizing that CTE incidence and prevalence remain unknown.
Key findings
- Exercise and sports participation reduce risk for cardiovascular disease, type 2 diabetes, hypertension, obesity, and stroke; increased baseline physical activity reduces dementia risk by 28% and Alzheimer’s disease risk by 45%, and midlife moderate activity is associated with a 39% lower risk of mild cognitive impairment.
- The CDC estimates 1.6–3.8 million sports/recreational concussions annually in the US, with 10–30% developing prolonged symptoms. High school football concussion rates were 0.21 per 1,000 athlete-exposures (A-E) in practice and 1.55 per 1,000 A-E in competition, versus 0.39 and 3.02 in collegiate football; soccer rates ranged from 1.38 per 1,000 game-time A-E for boys to 1.80 for girls; rugby mTBI incidence was 7.97 per 1,000 player game hours, with 313 of 3,207 players (9.8%) sustaining ≥1 mTBI and headgear associated with reduced risk (incident rate ratio 0.57).
- In the mTBI brain bank, 117 athlete brains were analyzed (115M:2F; age 14–98 years, mean 54.1), including 6 athletes who died within 6 months of a reported concussion. Among 103 neuropathologically confirmed CTE cases, co-existent Lewy body disease was found in 12%, motor neuron disease in 13%, Alzheimer’s disease in 15%, and frontotemporal lobar degeneration in 6%.
- CTE showed two clinical presentations: behavioral/mood symptoms with mean onset at 35 years and cognitive impairment with mean onset at 59 years; 86% of the behavioral/mood group progressed to cognitive symptoms, while 46% of the cognitive group developed behavioral/mood disorders. Pathologically, CTE is staged I–IV by PHF-tau topography; in the autopsy series, 33% of NFL players with Stage II or III CTE died by suicide, and suicide combined with drug or alcohol abuse accounted for 55% of deaths, while no Stage IV athletes died from suicide or drug overdose.
Methods
- Design: narrative review of the beneficial effects of sports/exercise and the less common adverse neuropathological outcomes, including concussion, second-impact syndrome, juvenile head trauma syndrome, catastrophic sudden death, and CTE.
- Data/sample: synthesis of published literature plus neuropathological case material from the mTBI brain bank at VA Boston/Boston University School of Medicine, including 117 athlete brains and a current experience of 103 neuropathologically confirmed CTE cases.
- Main analysis: descriptive synthesis; CTE cases were classified into Stages I–IV based on the topography of phosphorylated tau pathology, with additional assessment of TDP-43 pathology and axonal injury. No systematic search strategy or meta-analysis is described.
Limitations
- The paper states that the incidence and prevalence of CTE are not known and that precise determination will require longitudinal clinical studies and the ability to diagnose CTE during life.
- The paper states that the definition of second-impact syndrome is controversial and some investigators have challenged its existence; the relationship of second-impact syndrome to juvenile head trauma syndrome is uncertain; and CTE diagnostic and staging criteria are provisional, with formal consensus validation in progress.
- Evident from the text: this is a narrative review without a described systematic search; the autopsy series is subject to selection/referral bias from brain donation; and some cited clinical/epidemiological data rely on self-reported concussions or lack neuropathological verification (e.g., death certificates indicating AD or ALS in retired NFL players).
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113 Not checked yet · 14 Own interpretation · 14 No basis given · 13 Own result · 1 Partly supported · accuracy not yet measured
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the players who died within 6 months of a reported concussion, neuropathological examination showed multifocal and perivascular axonal injury in the corpus callosum, fornix, subcortical white matter, and cerebellum detectable using APP and phosphorylated neurofilament immuno-histochemistry (Fig. 1).”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Pathology of concussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 117 athletes in the mTBI brain bank are representative of athletes who sustain concussions, so neuropathological findings in them can be generalized to concussion pathology in athletes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Over the last 5 years, 117 brains of athletes, defined as a player over the age of 12 years who participated in organized sports for at least 3 consecutive years, have been analyzed at the mTBI brain bank at VA Boston/Boston University School of Medicine.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Pathology of concussion
plainn = 117- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 117 athletes in the mTBI brain bank are representative of athletes who sustain concussions, so neuropathological findings in them can be generalized to concussion pathology in athletes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was also striking perivascular microgliosis and astrocytosis.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Pathology of concussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 117 athletes in the mTBI brain bank are representative of athletes who sustain concussions, so neuropathological findings in them can be generalized to concussion pathology in athletes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our autopsy series, none of the athletes diagnosed with Stage IV CTE died from suicide or drug overdose (Table 2).”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
In the paper
“The majority of cases show TDP-43-positive neurites and inclusions in cerebral cortex, medial temporal lobe, diencephalon, and brainstem.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
In the paper
“Ab deposition is found in 13 % of cases as sparse diffuse and neuritic Ab plaques and vascular amyloid.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
In the paper
“In our current experience of 103 neuropathologically confirmed cases of CTE, there have been 13 individuals who developed a progressive motor neuron disease (MND) (13 %) [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > CTE with motor neuron disease
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plaincorrelationaln = 103- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
In the paper
“In all cases, there is a distinct TDP-43 proteinopathy affecting the brain and spinal cord (Fig. 6) [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > CTE with motor neuron disease
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plaincorrelationaln = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Stage IV disease, characterized by widespread neuronal loss and neurodegen-eration, correlates with advanced memory loss, executive dysfunction, and dementia.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Trauma exposure
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The clinical symptoms reported in subjects with each CTE stage are attributable to the CTE pathology rather than to other causes.
None of the sources cited for this claim have been checked yet.
In the paper
“Imaging studies indicate that physical exercise and higher fitness levels are associated with a reduced loss of hippocampal, gray and white matter volume with aging [34, 56, 57, 90, 189].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [34] Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, Elavsky S, Marquez DX, Hu L, Kramer AF (2006) Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci 61(11):1166–1170 source
- Not checked yetcites [56] Erickson KI, Miller DL, Roecklein KA (2012) The aging hippocampus: interactions between exercise, depression, and BDNF. Neurosci Rev J Bringing Neurobiol Neurol Psychiatry 18(1):82–97. doi: 10.1177/1073858410397054
- Not checked yetcites [57] Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 108(7):3017–3022. doi: 10.1073/pnas.1015950108 source
- Not checked yetcites [90] Hillman CH, Erickson KI, Kramer AF (2008) Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 9(1):58–65. doi: 10.1038/nrn2298 source
- Not checked yetcites [189] Voelcker-Rehage C, Godde B, Staudinger UM (2010) Physical and motor fitness are both related to cognition in old age. Eur J Neurosci 31(1):167–176. doi: 10.1111/j.1460-9568.2009.07014.x source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 81
- The quote only partly states this claim. 1
- Probably not a substantial claim. 11
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Clinical and functional impairments in cognition have also been correlated with the frequency of impacts to the head in high school and collegiate football players wearing helmet-mounted accelerometers [16, 121, 180], although not all helmet sensor studies have supported this relationship [81].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Chronic neurodegeneration including CTE
What the sources say
- Not checked yetcites [16] Breedlove EL, Robinson M, Talavage TM, Morigaki KE, Yoruk U, O’Keefe K, King J, Leverenz LJ, Gilger JW, Nauman EA (2012) Biomechanical correlates of symptomatic and asymptomatic neurophysiological impairment in high school football. J Biomech 45(7):1265–1272. doi: 10.1016/j.jbiomech.2012.01.034 source
- Partly supportedcites [121] McAllister TW, Flashman LA, Maerlender A, Greenwald RM, Beckwith JG, Tosteson TD, Crisco JJ, Brolinson PG, Duma SM, Duhaime AC, Grove MR, Turco JH (2012) Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes. Neurology 78(22):1777–1784. doi: 10.1212/WNL.0b013e3182582fe7 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [180] Talavage TM, Nauman EA, Breedlove EL, Yoruk U, Dye AE, Morigaki KE, Feuer H, Leverenz LJ (2013) Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion. J Neurotrauma. doi: 10.1089/neu.2010.1512
- Not checked yetcites [81] Gysland SM, Mihalik JP, Register-Mihalik JK, Trulock SC, Shields EW, Guskiewicz KM (2012) The relationship between subconcussive impacts and concussion history on clinical measures of neurologic function in collegiate football players. Ann Biomed Eng 40(1):14–22. doi: 10.1007/s10439-011-0421-3 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Focal accumulations of paired helical filament (PHF)-tau as neurofibrillary tangles (NFTs) and dot and spindle-shaped neurites around small blood vessels were found at the depth of the sulci in four cases; in two cases the PHF-tau immunoreactivity was consistent with Stage I CTE and in one case with Stage II CTE.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Pathology of concussion
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The 117 athletes in the mTBI brain bank are representative of athletes who sustain concussions, so neuropathological findings in them can be generalized to concussion pathology in athletes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of these 117 athletes, there were 115M:2F, ranging in age at death from 14 to 98 years, mean 54.1 – 22.3 years, including 6 athletes who died within 6 months of a reported concussion (6 M:0F, 14–28 years old at death, mean 18.6 – 3.75 years) (Table 1).”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Pathology of concussion
plainn = 117- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The 117 athletes in the mTBI brain bank are representative of athletes who sustain concussions, so neuropathological findings in them can be generalized to concussion pathology in athletes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, three of the six cases showed TDP-43 immunopositive neurites in the white matter and one case displayed mild beta amyloid (Ab) deposition in leptomeningeal vessels.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Pathology of concussion
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The 117 athletes in the mTBI brain bank are representative of athletes who sustain concussions, so neuropathological findings in them can be generalized to concussion pathology in athletes.
In the paper
“In Stage III CTE, most brains show reduced brain weight, mild frontal and temporal atrophy, and enlargement of the lateral and third ventricles. Septal abnormalities are common (50 %), including cavum septum pellucidum or septal fenestrations. There is often pallor of the locus coeruleus and substantia nigra, atrophy of the mammillary bodies, thalamus and hypothalamus, and thinning of the corpus”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our autopsy series, suicide claimed the life of 33 % NFL players with Stage II CTE and suicide combined with drug or alcohol abuse accounted for 55 % of deaths (Table 2).”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
In the paper
“Brains with Stage IV CTE usually show significant reduction of brain weight (Fig. 4), with pronounced atrophy of the frontal and temporal lobes, medial temporal lobe, and anterior thalamus. The hypothalamic floor is thinned, the mammillary bodies are darkly discolored and atrophied, and there is marked enlargement of the lateral and third ventricles.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plain- Asserted: unclear — It is unclear whether the authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
In the paper
“Microscopically, multiple foci of PHF-tau pathology are found at the depths of the sulci, commonly in the frontal, temporal, parietal, insular, and septal cortices (Figs. 2, 3, 6). NFTs are also found in superficial layers of the adjacent cerebral cortex, locus coeruleus and substantia innominata, but the medial temporal lobe structures are spared. Deep structures such as the substantia nigra, dor”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Symptoms in Stage III CTE include memory loss, executive dysfunction, explosivity, difficulty with attention and concentration, and aggression. 75 % of subjects in our series were considered cognitively impaired.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The clinical symptoms reported in subjects with each CTE stage are attributable to the CTE pathology rather than to other causes.
In the paper
“Microscopically, there are one or two isolated perivascular foci of PHF-tau NFTs and dot-like neuropil threads, most commonly found at the depths of cerebral sulci of the frontal cortex (Fig. 2) and usually in association with subpial PHF-tau positive astrocytes. NFTs are also commonly found in the locus coeruleus. About half of Stage I cases will also have abnormal TDP-43 inclusions within the s”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Symptoms in Stage IV CTE include severe executive dysfunction and memory loss with dementia. Most subjects also show profound loss of attention and concentration, language difficulties, explosivity, aggressive tendencies, paranoia, depression, and gait and visuospatial difficulties.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The clinical symptoms reported in subjects with each CTE stage are attributable to the CTE pathology rather than to other causes.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Stage II CTE in our series, Ab plaques were found only in an 87-year-old former NFL player, and vascular Ab was found only in a 28-year-old former NHL player.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As in Stage II, 33 % of former NFL players with Stage III CTE committed suicide, and suicide combined with drug or alcohol abuse led to 55 % of deaths in Stage III CTE in our series (Table 2).”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Symptoms in Stage II CTE are variable, but in some instances there are prominent behavioral and personality changes, paranoia, irritability, depression, headaches, and short-term memory loss.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The clinical symptoms reported in subjects with each CTE stage are attributable to the CTE pathology rather than to other causes.
In the paper
“Among American football players, the stage of CTE at death significantly correlates with age at death, number of years playing football, and number of years after retirement from football [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > American football
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most subjects (63 %) presented with motor weakness, atrophy, and fasciculations indistinguishable from sporadic ALS and developed mild cognitive and behavioral symptoms several years after the onset of motor symptoms.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > CTE with motor neuron disease
plainn = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
None of the sources cited for this claim have been checked yet.
In the paper
“In our current experience of 103 neuropathologically confirmed cases of CTE, co-existent LBD was found in 12 (12 %) cases, MND in 13 (13 %), AD in 15 (15 %), and FTLD in 6 (6 %), suggesting that either repetitive trauma or the accumulation of tau pathology in CTE provokes the deposition of other abnormal proteins involved in neurodegeneration [127, 128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Chronic traumatic encephalopathy with co-morbid degenerative disease
What the sources say
- Not checked yetcites [127] McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, Perl DP, Hedley-Whyte ET, Price B, Sullivan C, Morin P, Lee HS, Kubilus CA, Daneshvar DH, Wulff M, Budson AE (2010) TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol. doi: 10.1097/NEN.0b013e3181ee7d85 source
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plaincorrelationaln = 103- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our series, CTE was found in the brains of five hockey players, including four former NHL players.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Ice hockey
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Stage II and III disease correlate with the onset of overt symptoms and mental distress, including depression and death due to suicide, alcohol, or drug overdose.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Trauma exposure
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The clinical symptoms reported in subjects with each CTE stage are attributable to the CTE pathology rather than to other causes.
None of the sources cited for this claim have been checked yet.
In the paper
“improves cognitive function, learning and memory, and significantly moderates age-related cognitive decline [2, 97, 104, 110, 187, 188, 200], reviewed in [10].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [2] Ang ET, Dawe GS, Wong PT, Moochhala S, Ng YK (2006) Alterations in spatial learning and memory after forced exercise. Brain Res 1113(1):186–193. doi: 10.1016/j.brainres.2006.07.023 source
- Not checked yetcites [97] Huang AM, Jen CJ, Chen HF, Yu L, Kuo YM, Chen HI (2006) Compulsive exercise acutely upregulates rat hippocampal brain-derived neurotrophic factor. J Neural Transm 113(7):803–811. doi: 10.1007/s00702-005-0359-4 source
- Not checked yetcites [104] Lakka TA, Laaksonen DE (2007) Physical activity in prevention and treatment of the metabolic syndrome. Applied physiology, nutrition, and metabolism. Physiologie appliquee, nutrition et metabolisme 32(1):76–88. doi: 10.1139/h06-113 source
- Not checked yetcites [110] Leung FP, Yung LM, Laher I, Yao X, Chen ZY, Huang Y (2008) Exercise, vascular wall and cardiovascular diseases: an update (Part 1). Sports Med 38(12):1009–1024. doi: 10.2165/00007256-200838120-00005 source
- Not checked yetcites [187] van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25(38):8680–8685. doi: 10.1523/JNEUROSCI.1731-05.2005 source
- Not checked yetcites [188] Vaynman S, Gomez-Pinilla F (2006) Revenge of the “sit”: how lifestyle impacts neuronal and cognitive health through molecular systems that interface energy metabolism with neuronal plasticity. J Neurosci Res 84(4):699–715. doi: 10.1002/jnr.20979 source
- Not checked yetcites [200] Yung LM, Laher I, Yao X, Chen ZY, Huang Y, Leung FP (2009) Exercise, vascular wall and cardiovascular diseases: an update (part 2). Sports Med 39(1):45–63. doi: 10.2165/00007256-200939010-00004 source
- Not checked yetcites [10] Bherer L, Erickson KI, Liu-Ambrose T (2013) A review of the effects of physical activity and exercise on cognitive and brain functions in older adults. J Aging Res 2013:657508. doi: 10.1155/2013/657508
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Prospective epidemiological studies show that increased baseline physical activity reduces the risk of developing dementia by 28 % and of developing AD by 45 % [58, 83].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [58] Erickson KI, Weinstein AM, Lopez OL (2012) Physical activity, brain plasticity, and Alzheimer’s disease. Arch Med Res 43(8):615–621. doi: 10.1016/j.arcmed.2012.09.008 source
- Not checked yetcites [83] Hamer M, Chida Y (2009) Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol Med 39(1):3–11. doi: 10.1017/S0033291708003681 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In the hippocampus, BDNF promotes the production and survival of new neurons from stem cells and the integration of new neurons into existing neuronal circuits [141], reviewed in [160].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [141] Murer MG, Yan Q, Raisman-Vozari R (2001) Brain-derived neurotrophic factor in the control human brain, and in Alzheimer’s disease and Parkinson’s disease. Prog Neurobiol 63(1):71–124 source
- Not checked yetcites [160] Rothman SM, Griffioen KJ, Wan R, Mattson MP (2012) Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health. Ann N Y Acad Sci 1264(1):49–63. doi: 10.1111/j.1749-6632.2012.06525.x source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Exercise training is also associated with improved endothelial function, decreased arterial stiffness, and greater vascular reactivity associated with coronary artery disease, heart failure, and peripheral vascular disease [110].”
§ The neuropathology of sport > The benefits of exercise and sports participation > The physical benefits of sports participation
What the sources say
- Not checked yetcites [110] Leung FP, Yung LM, Laher I, Yao X, Chen ZY, Huang Y (2008) Exercise, vascular wall and cardiovascular diseases: an update (Part 1). Sports Med 38(12):1009–1024. doi: 10.2165/00007256-200838120-00005 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Exercise has also been shown to be neuroprotective, to delay the onset and progression, and reduce the risk for many neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD) [17, 39, 58, 89, 108, 163, 193, 199].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [17] Buchman AS, Boyle PA, Yu L, Shah RC, Wilson RS, Bennett DA (2012) Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology 78(17):1323–1329. doi: 10.1212/WNL.0b013e3182535d35 source
- Not checked yetcites [39] Cotman CW, Berchtold NC, Christie LA (2007) Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 30(9):464–472. doi: 10.1016/j.tins.2007.06.011 source
- Not checked yetcites [58] Erickson KI, Weinstein AM, Lopez OL (2012) Physical activity, brain plasticity, and Alzheimer’s disease. Arch Med Res 43(8):615–621. doi: 10.1016/j.arcmed.2012.09.008 source
- Not checked yetcites [89] Heyn P, Abreu BC, Ottenbacher KJ (2004) The effects of exercise training on elderly persons with cognitive impairment and dementia: a meta-analysis. Arch Phys Med Rehabil 85(10):1694–1704 source
- Not checked yetcites [108] Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, Greenop KR, Almeida OP (2008) Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 300(9):1027–1037. doi: 10.1001/jama.300.9.1027 source
- Not checked yetcites [163] Sattler C, Erickson KI, Toro P, Schroder J (2011) Physical fitness as a protective factor for cognitive impairment in a prospective population-based study in Germany. J Alzheimers Dis 26(4):709–718. doi: 10.3233/JAD-2011-110548 source
- Not checked yetcites [193] Weuve J, Kang JH, Manson JE, Breteler MM, Ware JH, Grodstein F (2004) Physical activity, including walking, and cognitive function in older women. JAMA 292(12):1454–1461. doi: 10.1001/jama.292.12.1454 source
- Not checked yetcites [199] Yaffe K, Barnes D, Nevitt M, Lui LY, Covinsky K (2001) A prospective study of physical activity and cognitive decline in elderly women: women who walk. Arch Intern Med 161(14):1703–1708 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Higher levels of physical activity, exercise training, and overall cardiorespiratory fitness reduce the risk for hypertension, obesity, type 2 diabetes mellitus, stroke, and metabolic syndrome, as well as lower cardiovascular mortality [104, 110, 178, 200].”
§ The neuropathology of sport > The benefits of exercise and sports participation > The physical benefits of sports participation
What the sources say
- Not checked yetcites [104] Lakka TA, Laaksonen DE (2007) Physical activity in prevention and treatment of the metabolic syndrome. Applied physiology, nutrition, and metabolism. Physiologie appliquee, nutrition et metabolisme 32(1):76–88. doi: 10.1139/h06-113 source
- Not checked yetcites [110] Leung FP, Yung LM, Laher I, Yao X, Chen ZY, Huang Y (2008) Exercise, vascular wall and cardiovascular diseases: an update (Part 1). Sports Med 38(12):1009–1024. doi: 10.2165/00007256-200838120-00005 source
- Not checked yetcites [178] Swift DL, Lavie CJ, Johannsen NM, Arena R, Earnest CP, O’Keefe JH, Milani RV, Blair SN, Church TS (2013) Physical activity, cardiorespiratory fitness, and exercise training in primary and secondary coronary prevention. Circ J Off J Jpn Circ Soc 77(2):281–292
- Not checked yetcites [200] Yung LM, Laher I, Yao X, Chen ZY, Huang Y, Leung FP (2009) Exercise, vascular wall and cardiovascular diseases: an update (part 2). Sports Med 39(1):45–63. doi: 10.2165/00007256-200939010-00004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“BDNF acts on neurons to promote growth, increase synaptic plasticity, and enhance resistance to injury and neurodegeneration.”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Physical activity increases antioxidant enzymes, including superoxide dismutase and heat shock proteins, and reduces reactive oxygen species [178].”
§ The neuropathology of sport > The benefits of exercise and sports participation > The physical benefits of sports participation
What the sources say
- Not checked yetcites [178] Swift DL, Lavie CJ, Johannsen NM, Arena R, Earnest CP, O’Keefe JH, Milani RV, Blair SN, Church TS (2013) Physical activity, cardiorespiratory fitness, and exercise training in primary and secondary coronary prevention. Circ J Off J Jpn Circ Soc 77(2):281–292
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“physical exercise also directly promotes neurogenesis, cell survival [187], synaptogenesis, synaptic plasticity [54, 96] and angiogenesis [99]”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [187] van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25(38):8680–8685. doi: 10.1523/JNEUROSCI.1731-05.2005 source
- Not checked yetcites [54] Eadie BD, Redila VA, Christie BR (2005) Voluntary exercise alters the cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density. J Comp Neurol 486(1):39–47. doi: 10.1002/cne.20493 source
- Not checked yetcites [96] Hu S, Ying Z, Gomez-Pinilla F, Frautschy SA (2009) Exercise can increase small heat shock proteins (sHSP) and pre- and post-synaptic proteins in the hippocampus. Brain Res 1249:191–201. doi: 10.1016/j.brainres.2008.10.054 source
- Not checked yetcites [99] Isaacs KR, Anderson BJ, Alcantara AA, Black JE, Greenough WT (1992) Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning. J Cereb Blood Flow Metab 12(1):110–119. doi: 10.1038/jcbfm.1992.14 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cross-sectional studies show that improved physical fitness is associated with more efficient cognitive functions and longitudinal studies show less cognitive decline in working memory, processing speed, attention, and executive function in older adults without dementia [170].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [170] Smith PJ, Blumenthal JA, Hoffman BM, Cooper H, Strauman TA, Welsh-Bohmer K, Browndyke JN, Sherwood A (2010) Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med 72(3):239–252. doi: 10.1097/PSY.0b013e3181d14633 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Aerobic exercise increases hip-pocampal and cortical volume and significantly improves spatial memory after 1 year [57].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [57] Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 108(7):3017–3022. doi: 10.1073/pnas.1015950108 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Regular exercise produces beneficial effects in high-density lipoprotein-cholesterol levels, glucose control, weight control, and resting heart rate and blood pressure [178].”
§ The neuropathology of sport > The benefits of exercise and sports participation > The physical benefits of sports participation
What the sources say
- Not checked yetcites [178] Swift DL, Lavie CJ, Johannsen NM, Arena R, Earnest CP, O’Keefe JH, Milani RV, Blair SN, Church TS (2013) Physical activity, cardiorespiratory fitness, and exercise training in primary and secondary coronary prevention. Circ J Off J Jpn Circ Soc 77(2):281–292
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Exercise training also suppresses chronic low-grade inflammation and reduces levels of C-reactive protein and TNF-alpha [152].”
§ The neuropathology of sport > The benefits of exercise and sports participation > The physical benefits of sports participation
What the sources say
- Not checked yetcites [152] Petersen AM, Pedersen BK (2005) The anti-inflammatory effect of exercise. J Appl Physiol (1985) 98(4):1154–1162. doi: 10.1152/japplphysiol.00164.2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“early post-injury exercise has been shown to reverse memory deficits and inhibit the progression of neurodegeneration following TBI [27].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [27] Chen MF, Huang TY, Kuo YM, Yu L, Chen HI, Jen CJ (2013) Early postinjury exercise reverses memory deficits and retards the progression of closed-head injury in mice. J Physiol 591(Pt 4):985–1000. doi: 10.1113/jphysiol.2012.241125 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“71 % of the affected athletes have been American football players, usually at the high school level, but younger players and collegiate athletes have occasionally been reported.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Second-impact syndrome
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Treadmill exercise also improves hippocampus-dependent spatial learning and memory as well as aversive memory [2, 3, 25, 97, 112, 174, 186, 187].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [2] Ang ET, Dawe GS, Wong PT, Moochhala S, Ng YK (2006) Alterations in spatial learning and memory after forced exercise. Brain Res 1113(1):186–193. doi: 10.1016/j.brainres.2006.07.023 source
- Not checked yetcites [3] Ang ET, Gomez-Pinilla F (2007) Potential therapeutic effects of exercise to the brain. Curr Med Chem 14(24):2564–2571 source
- Not checked yetcites [25] Chen HI, Lin LC, Yu L, Liu YF, Kuo YM, Huang AM, Chuang JI, Wu FS, Liao PC, Jen CJ (2008) Treadmill exercise enhances passive avoidance learning in rats: the role of down-regulated serotonin system in the limbic system. Neurobiol Learn Mem 89(4):489–496. doi: 10.1016/j.nlm.2007.08.004 source
- Not checked yetcites [97] Huang AM, Jen CJ, Chen HF, Yu L, Kuo YM, Chen HI (2006) Compulsive exercise acutely upregulates rat hippocampal brain-derived neurotrophic factor. J Neural Transm 113(7):803–811. doi: 10.1007/s00702-005-0359-4 source
- Not checked yetcites [112] Liu YF, Chen HI, Yu L, Kuo YM, Wu FS, Chuang JI, Liao PC, Jen CJ (2008) Upregulation of hippocampal TrkB and synaptotagmin is involved in treadmill exercise-enhanced aversive memory in mice. Neurobiol Learn Mem 90(1):81–89. doi: 10.1016/j.nlm.2008.02.005 source
- Not checked yetcites [174] Soya H, Nakamura T, Deocaris CC, Kimpara A, Iimura M, Fujikawa T, Chang H, McEwen BS, Nishijima T (2007) BDNF induction with mild exercise in the rat hippocampus. Biochem Biophys Res Commun 358(4):961–967. doi: 10.1016/j.bbrc.2007.04.173 source
- Not checked yetcites [186] van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96(23):13427–13431 source
- Not checked yetcites [187] van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25(38):8680–8685. doi: 10.1523/JNEUROSCI.1731-05.2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“with the largest number of deaths reported in American football (148 [57 %]), including 17 high school athletes who sustained concussions shortly before a fatal head trauma (“second-impact syndrome”) [181].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Sudden death in young athletes
What the sources say
- Not checked yetcites [181] Thomas M, Haas TS, Doerer JJ, Hodges JS, Aicher BO, Garberich RF, Mueller FO, Cantu RC, Maron BJ (2011) Epidemiology of sudden death in young, competitive athletes due to blunt trauma. Pediatrics 128(1):e1–e8. doi: 10.1542/peds.2010-2743 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“exercise also improves motor performance in individuals with Parkinson’s disease [153], lowers disability in multiple sclerosis [161], improves functionality in individuals with motor neuron disease [46], and improves cognitive, mood and motor recovery from TBI, although the precise timing and intensity of the beneficial exercise after TBI remain to be determined [62, 197].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [153] Petzinger GM, Fisher BE, McEwen S, Beeler JA, Walsh JP, Jakowec MW (2013) Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson’s disease. Lancet Neurol 12(7):716–726. doi: 10.1016/S1474-4422(13)70123-6 source
- Not checked yetcites [161] Sa MJ (2013) Exercise therapy and multiple sclerosis: a systematic review. J Neurol. doi: 10.1007/s00415-013-7183-9
- Not checked yetcites [46] Dal Bello-Haas V, Florence JM (2013) Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease. The Cochrane Database Syst Rev 5:CD005229. doi: 10.1002/14651858.CD005229.pub3 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Second-impact syndrome (SIS) occurs when an athlete sustains an initial mild head injury or concussion, then suffers a second head injury before the symptoms associated with the first impact have cleared, with resultant diffuse cerebral swelling and grave deterioration [19, 20, 113, 133, 137, 164].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Second-impact syndrome
What the sources say
- Not checked yetcites [19] Cantu R, Gean A (2010) Second impact syndrome in a small SDH: an uncommon catastrophic result of repetitive head injury with a characteristic imaging appearance. J Neurotrauma. doi: 10.1089/neu.2010.1334 source
- Not checked yetcites [20] Cantu RC (1998) Second-impact syndrome. Clin Sports Med 17(1):37–44 source
- Not checked yetcites [113] Logan SM, Bell GW, Leonard JC (2001) Acute subdural hematoma in a high school football player after 2 unreported episodes of head trauma: a case report. J Athl Train 36(4):433–436
- Not checked yetcites [133] Miele VJ, Carson L, Carr A, Bailes JE (2004) Acute on chronic subdural hematoma in a female boxer: a case report. Med Sci Sports Exerc 36(11):1852–1855 source
- Not checked yetcites [137] Mori T, Katayama Y, Kawamata T (2006) Acute hemispheric swelling associated with thin subdural hematomas: pathophysiology of repetitive head injury in sports. Acta Neurochirurgica Supplement 96:40–43 source
- Not checked yetcites [164] Saunders RL, Harbaugh RE (1984) The second impact in catastrophic contact-sports head trauma. JAMA 252(4):538–539 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Analysis of the 30-year US National Registry of Sudden Death in Young Athletes from 1980 to 2009 found 1,827 deaths in athletes aged 21 years or younger (mean 16 – 2 years; 90 % male) including 261 (14 %) due to trauma, most often to the head and neck.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Sudden death in young athletes
What the sources say
- Not checked yetcites [181] Thomas M, Haas TS, Doerer JJ, Hodges JS, Aicher BO, Garberich RF, Mueller FO, Cantu RC, Maron BJ (2011) Epidemiology of sudden death in young, competitive athletes due to blunt trauma. Pediatrics 128(1):e1–e8. doi: 10.1542/peds.2010-2743 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Rodents that run voluntarily on running wheels exhibit increased numbers of dendritic spines and synapses in hippocampal neurons, increased neurogenesis, and improved performance in some behavioral tests of cognitive function [59, 185].”
§ The neuropathology of sport > The benefits of exercise and sports participation > Exercise as a neuroprotectant against age-related cognitive decline
What the sources say
- Not checked yetcites [59] Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague–Dawley rats in vivo. Neuroscience 124(1):71–79. doi: 10.1016/j.neuroscience.2003.09.029 source
- Not checked yetcites [185] Valois RF, Zullig KJ, Huebner ES, Drane JW (2004) Physical activity behaviors and perceived life satisfaction among public high school adolescents. J Sch Health 74(2):59–65 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“All reported cases of SIS have involved young athletes, predominantly males (90 %) ranging in age from 10 to 24 years, mean age 17.9 years [137].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Second-impact syndrome
What the sources say
- Not checked yetcites [137] Mori T, Katayama Y, Kawamata T (2006) Acute hemispheric swelling associated with thin subdural hematomas: pathophysiology of repetitive head injury in sports. Acta Neurochirurgica Supplement 96:40–43 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The mortality rate was 0.11 in 100,000 participants (95 % confidence interval 0.08–0.15)”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Sudden death in young athletes
What the sources say
- Not checked yetcites [181] Thomas M, Haas TS, Doerer JJ, Hodges JS, Aicher BO, Garberich RF, Mueller FO, Cantu RC, Maron BJ (2011) Epidemiology of sudden death in young, competitive athletes due to blunt trauma. Pediatrics 128(1):e1–e8. doi: 10.1542/peds.2010-2743 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In a cohort of 3,207 male nonprofessional rugby players followed for one or more seasons, the incidence of mTBI was 7.97 per 1,000 player game hours, with 313 players (9.8 %) sustaining 1 or more mTBIs during the study.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Acute concussive injury
What the sources say
- Not checked yetcites [94] Hong YT, Veenith T, Dewar D, Outtrim JG, Mani V, Williams C, Pimlott S, Hutchinson PJ, Tavares A, Canales R, Mathis CA, Klunk WE, Aigbirhio FI, Coles JP, Baron JC, Pickard JD, Fryer TD, Stewart W, Menon DK (2013) Amyloid Imaging With Carbon 11-Labeled Pittsburgh Compound B for Traumatic Brain Injury. JAMA Neurol. doi: 10.1001/jamaneurol.2013.4847 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“high school football was associated with concussion rate of 0.21 per 1,000 athlete exposures (A–E) in practice and 1.55 concussions per 1,000 A–E in competitions, compared to 0.39 per 1,000 A-E in practice and a rate of 3.02 concussions per 1,000 A-E in competitions in collegiate football players [68].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Acute concussive injury
What the sources say
- Not checked yetcites [68] Gessel LM, Fields SK, Collins CL, Dick RW, Comstock RD (2007) Concussions among United States high school and collegiate athletes. J Athl Train 42(4):495–503
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Symptoms from concussion and other forms of mTBI are usually self-limited and resolve spontaneously over a period of several weeks, although 10–30 % of individuals develop prolonged symptoms.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Acute concussive injury
What the sources say
- Not checked yetcites [51] Dean PJ, Sterr A (2013) Long-term effects of mild traumatic brain injury on cognitive performance. Frontiers Hum Neurosci 7:30. doi: 10.3389/fnhum.2013.00030
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Traumatic axonal injury (TAI) does not uniformly affect all axonal populations; smaller, unmyelinated axons may be more susceptible to damage from concussive forces than larger myelinated axons [158].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Pathophysiology of concussion
What the sources say
- Not checked yetcites [158] Reeves TM, Phillips LL, Povlishock JT (2005) Myelinated and unmyelinated axons of the corpus callosum differ in vulnerability and functional recovery following traumatic brain injury. Exp Neurol 196(1):126–137. doi: 10.1016/j.expneurol.2005.07.014 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Estimates of the concussion rate in high school soccer range from 1.38 concussions per 1,000 game time A-E for boys to 1.80 for girls [68].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Acute concussive injury
What the sources say
- Not checked yetcites [68] Gessel LM, Fields SK, Collins CL, Dick RW, Comstock RD (2007) Concussions among United States high school and collegiate athletes. J Athl Train 42(4):495–503
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Studies using accelerometers to measure the peak accelerations of the head during soccer heading found linear accelerations as high as 54.7g in high school players heading a soccer ball kicked from a distance of 30 yards, more than the average peak accelerations of 29.2 or 35g that occur in football or ice hockey [142].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Acute concussive injury
What the sources say
- Not checked yetcites [142] Naunheim RS, Standeven J, Richter C, Lewis LM (2000) Comparison of impact data in hockey, football, and soccer. J Trauma 48(5):938–941 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Pathological studies of acute concussion and PCS are rare and often include subjects with more severe traumatic injuries, but multifocal traumatic axonal injury TAI, microhemorrhage, and microglial activation have been reported [12, 150].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Pathology of concussion
What the sources say
- Not checked yetcites [12] Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ (1994) Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344(8929):1055–1056 source
- Not checked yetcites [150] Oppenheimer DR (1968) Microscopic lesions in the brain following head injury. J Neurol Neurosurg Psychiatry 31(4):299–306 source
plainn = 5- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The Centers for Disease Control estimates that 1.6 to 3.8 million concussions occur in sports and recreational activities annually in the US [47].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Acute concussive injury
What the sources say
- Not checked yetcites [47] Daneshvar DH, Nowinski CJ, McKee AC, Cantu RC (2011) The epidemiology of sport-related concussion. Clin Sports Med 30(1):1–17, vii. doi: 10.1016/j.csm.2010.08.006 source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Diffusion tensor imaging (DTI), however, provides information about the white matter microstructure and fiber tract integrity and is emerging as a valuable tool in refining the diagnosis, prognosis, and management of mTBI [5, 149, 196].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Imaging studies after concussion
What the sources say
- Not checked yetcites [5] Aoki Y, Inokuchi R, Gunshin M, Yahagi N, Suwa H (2012) Diffusion tensor imaging studies of mild traumatic brain injury: a meta-analysis. J Neurol Neurosurg Psychiatry 83(9):870–876. doi: 10.1136/jnnp-2012-302742 source
- Not checked yetcites [149] Oni MB, Wilde EA, Bigler ED, McCauley SR, Wu TC, Yallampalli R, Chu Z, Li X, Hunter JV, Vasquez AC, Levin HS (2010) Diffusion tensor imaging analysis of frontal lobes in pediatric traumatic brain injury. J Child Neurol 25(8):976–984. doi: 10.1177/0883073809356034 source
- Not checked yetcites [196] Wilde EA, McCauley SR, Hunter JV, Bigler ED, Chu Z, Wang ZJ, Hanten GR, Troyanskaya M, Yallampalli R, Li X, Chia J, Levin HS (2008) Diffusion tensor imaging of acute mild traumatic brain injury in adolescents. Neurology 70(12):948–955. doi: 10.1212/01.wnl.0000305961.68029.54 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Depression in these athletes is also associated with increased fractional anisotropy on DTI, as well as white matter abnormalities on structural imaging [87, 176].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Chronic neurodegeneration including CTE
What the sources say
- Not checked yetcites [87] Hart J Jr, Kraut MA, Womack KB, Strain J, Didehbani N, Bartz E, Conover H, Mansinghani S, Lu H, Cullum CM (2013) Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. JAMA Neurol 70(3):326–335. doi: 10.1001/2013.jamaneurol.340 source
- Not checked yetcites [176] Strain J, Didehbani N, Cullum CM, Mansinghani S, Conover H, Kraut MA, Hart J Jr, Womack KB (2013) Depressive symptoms and white matter dysfunction in retired NFL players with concussion history. Neurology 81(1):25–32. doi: 10.1212/WNL.0b013e318299ccf8 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“the severity of symptoms after mTBI correlates with reduction of white matter integrity on DTI, suggesting that persistent microstructural brain injury underlies the symptoms of PCS [45].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Imaging studies after concussion
What the sources say
- Not checked yetcites [45] Cubon VA, Putukian M, Boyer C, Dettwiler A (2011) A diffusion tensor imaging study on the white matter skeleton in individuals with sports-related concussion. J Neurotrauma 28(2):189–201. doi: 10.1089/neu2010.1430 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In addition to a different topography of NFTs in CTE compared to AD, the size of individual NFTs in CTE is generally larger and the neurites are more dot like and spindle shaped [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Neuropathology of CTE
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Astrocytic PHF-tau pathology in CTE is predominantly 4R tau immunopositive, but more widely distributed than that reported in the medial temporal lobe in aging and AD [103, 114].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
What the sources say
- Not checked yetcites [103] Lace G, Ince PG, Brayne C, Savva GM, Matthews FE, de Silva R, Simpson JE, Wharton SB (2012) Mesial temporal astrocyte tau pathology in the MRC-CFAS ageing brain cohort. Dement Geriatr Cogn Disord 34(1):15–24. doi: 10.1159/000341581 source
- Not checked yetcites [114] Lopez-Gonzalez I, Carmona M, Blanco R, Luna-Munoz J, Martinez-Mandonado A, Mena R, Ferrer I (2013) Characterization of thorn-shaped astrocytes in white matter of temporal lobe in Alzheimer’s disease brains. Brain Pathol 23(2):144–153. doi: 10.1111/j.1750-3639.2012.00627.x source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The clinical symptoms associated with this disease were examined in case summaries throughout the twentieth century; however, the disease presentation described in these reports was inconsistent [38, 65, 92, 100, 126].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Clinical symptoms in CTE
What the sources say
- Not checked yetcites [38] Corsellis JA, Bruton CJ, Freeman-Browne D (1973) The aftermath of boxing. Psychol Med 3(3):270–303 source
- Not checked yetcites [65] Geddes JF, Vowles GH, Nicoll JA, Revesz T (1999) Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol (Berl) 98(2):171–178 source
- Not checked yetcites [92] Hof PR, Knabe R, Bovier P, Bouras C (1991) Neuropathological observations in a case of autism presenting with self-injury behavior. Acta Neuropathol (Berl) 82(4):321–326 source
- Not checked yetcites [100] Jordan BD, Kanik AB, Horwich MS, Sweeney D, Relkin NR, Petito CK, Gandy S (1995) Apolipoprotein E epsilon 4 and fatal cerebral amyloid angiopathy associated with dementia pugilistica. Ann Neurol 38(4):698–699. doi: 10.1002/ana.410380429 source
- Not checked yetcites [126] McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA (2009) Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 68(7):709–735. doi: 10.1097/NEN.0b013e3181a9d503 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Geddes described argyrophilic, PHF-tau positive neocortical NFTs and neurites, strikingly arranged in groups around small intracortical blood vessels, in the absence of Ab [65], a feature that has recently been found to distinguish even early stages of CTE from other tauopathies.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Neuropathology of CTE
What the sources say
- Not checked yetcites [65] Geddes JF, Vowles GH, Nicoll JA, Revesz T (1999) Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol (Berl) 98(2):171–178 source
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Neuronal loss was noted in the cerebellar tonsils and substantia nigra with Cresyl violet stain, and there was neurofibrillary degeneration of the substantia nigra and cerebral cortex using Von Braunmühl’s silver stain.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Neuropathology of CTE
What the sources say
- Not checked yetcites [38] Corsellis JA, Bruton CJ, Freeman-Browne D (1973) The aftermath of boxing. Psychol Med 3(3):270–303 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although some studies have interpreted phosphorylated tau abnormalities in the locus coeruleus to be an early stage of AD pathology [15], young control subjects were not screened for a history of exposure to mTBI despite the fact that mTBI is common among young individuals and that 17 % of the control subjects died from acute trauma or accidental death.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
What the sources say
- Not checked yetcites [15] Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol (Berl) 121(2):171–181. doi: 10.1007/s00401-010-0789-4 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Stress and resultant axonal injury are greatest at the interface of two tissues with differing viscoelastic properties (such as between blood vessels and brain, or between gray and white matter) and the depths of the cortical sulci are areas of stress concentration [11, 28, 33].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
What the sources say
- Not checked yetcites [11] Blennow K, Hardy J, Zetterberg H (2012) The neuropathology and neurobiology of traumatic brain injury. Neuron 76(5):886–899. doi: 10.1016/j.neuron.2012.11.021 source
- Not checked yetcites [28] Chen XH, Siman R, Iwata A, Meaney DF, Trojanowski JQ, Smith DH (2004) Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am J Pathol 165(2):357–371 source
- Not checked yetcites [33] Cloots RJ, Gervaise HM, van Dommelen JA, Geers MG (2008) Biomechanics of traumatic brain injury: influences of the morphologic heterogeneities of the cerebral cortex. Ann Biomed Eng 36(7):1203–1215. doi: 10.1007/s10439-008-9510-3 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CTE is similar to AD in its tau isoform profile and phosphorylation state [165], and neuronal tau pathology is immunoreactive to both 3R and 4R tau [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
What the sources say
- Not checked yetcites [165] Schmidt ML, Zhukareva V, Newell KL, Lee VM, Trojanowski JQ (2001) Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer’s disease. Acta Neuropathol (Berl) 101(5):518–524 source
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Specifically, two presentations of CTE were found, one that consisted of behavioral and mood symptoms usually appearing in the third decade of life (mean age at onset of 35 years) and another consisting of cognitive impairment and memory loss developing in the fifth decade (mean age at onset of 59 years).”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Clinical symptoms in CTE
What the sources say
- Not checked yetcites [175] Stern RA, Daneshvar DH, Baugh CM, Seichepine DR, Montenigro PH, Riley DO, Fritts NG, Stamm JM, Robbins CA, McHale L, I. S, Stein TD, V. A, Goldstein LE, Budson AE, Kowall NW, Nowinski CJ, Cantu RC, McKee AC (2013) Clinical presentation of neuropathologically-confirmed chronic traumatic encephalopathy in athletes. Neurology (in Press) source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Additionally, medial temporal lobe PHF-tau pathology is not found in early stages of CTE, while it is considered the hallmark of emerging or preclinical AD pathology.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Characteristically, the locus coeruleus shows neurofibrillary PHF-tau pathology in early stages of CTE, which can be substantial even in individuals under the age of 30.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This stage is most likely preclinical, although some subjects with Stage I pathology report vague and non-specific symptoms such as headache, loss of attention and concentration, short-term memory difficulties, and depression.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Stages of CTE pathology
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
None of the sources cited for this claim have been checked yet.
In the paper
“Factors that might contribute to increased vulnerability to trauma in the developing brain include age-specific differences in myelination rates, synaptic pruning, neurotrophic factor levels, brain water content, cerebral blood flow, and glucocorticoid receptor expression [69, 76, 183].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
What the sources say
- Not checked yetcites [69] Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL (1999) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2(10):861–863. doi: 10.1038/13158 source
- Not checked yetcites [76] Grieve SM, Korgaonkar MS, Clark CR, Williams LM (2011) Regional heterogeneity in limbic maturational changes: evidence from integrating cortical thickness, volumetric and diffusion tensor imaging measures. Neuroimage 55(3):868–879. doi: 10.1016/j.neuroimage.2010.12.087 source
- Not checked yetcites [183] Uematsu A, Matsui M, Tanaka C, Takahashi T, Noguchi K, Suzuki M, Nishijo H (2012) Developmental trajectories of amygdala and hippocampus from infancy to early adulthood in healthy individuals. PLoS ONE 7(10):e46970. doi: 10.1371/journal.pone.0046970PONE-D-12-12929 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition to PHF-tau pathology, axonal pathology is present at all stages of CTE and becomes more severe as CTE stage advances [72, 128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Axonal pathology in CTE
What the sources say
- Not checked yetcites [72] Goldstein LE, Fisher AM, Tagge CA, Zhang XL, Velisek L, Sullivan JA, Upreti C, Kracht JM, Ericsson M, Wojnarowicz MW, Goletiani CJ, Maglakelidze GM, Casey N, Moncaster JA, Minaeva O, Moir RD, Nowinski CJ, Stern RA, Cantu RC, Geiling J, Blusztajn JK, Wolozin BL, Ikezu T, Stein TD, Budson AE, Kowall NW, Chargin D, Sharon A, Saman S, Hall GF, Moss WC, Cleveland RO, Tanzi RE, Stanton PK, McKee AC (2012) Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med 4(134):134ra60. doi: 10.1126/scitranslmed.3003716 source
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, the developing brain may be more susceptible to poor outcomes following TBI. Studies have suggested that children and adolescents experience prolonged recovery rates after TBI compared to adults [61] and poorer outcome [70].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
What the sources say
- Not checked yetcites [61] Field M, Collins MW, Lovell MR, Maroon J (2003) Does age play a role in recovery from sports-related concussion? A comparison of high school and collegiate athletes. J Pediatr 142(5):546–553. doi: 10.1067/mpd.2003.190 source
- Not checked yetcites [70] Giza CC, Griesbach GS, Hovda DA (2005) Experience-dependent behavioral plasticity is disturbed following traumatic injury to the immature brain. Behav Brain Res 157(1):11–22. doi: 10.1016/j.bbr.2004.06.003 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, despite evidence for Ab deposition in moderate to severe TBI [94], Ab plaques have not been found in early or mild stages of CTE in young individuals [65, 66, 72, 91, 126] but occur in older subjects with CTE in association with increased age at death [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Ab in CTE
What the sources say
- Not checked yetcites [94] Hong YT, Veenith T, Dewar D, Outtrim JG, Mani V, Williams C, Pimlott S, Hutchinson PJ, Tavares A, Canales R, Mathis CA, Klunk WE, Aigbirhio FI, Coles JP, Baron JC, Pickard JD, Fryer TD, Stewart W, Menon DK (2013) Amyloid Imaging With Carbon 11-Labeled Pittsburgh Compound B for Traumatic Brain Injury. JAMA Neurol. doi: 10.1001/jamaneurol.2013.4847 source
- Not checked yetcites [65] Geddes JF, Vowles GH, Nicoll JA, Revesz T (1999) Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol (Berl) 98(2):171–178 source
- Not checked yetcites [66] Geddes JF, Vowles GH, Robinson SF, Sutcliffe JC (1996) Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathol Appl Neurobiol 22(1):12–16 source
- Not checked yetcites [72] Goldstein LE, Fisher AM, Tagge CA, Zhang XL, Velisek L, Sullivan JA, Upreti C, Kracht JM, Ericsson M, Wojnarowicz MW, Goletiani CJ, Maglakelidze GM, Casey N, Moncaster JA, Minaeva O, Moir RD, Nowinski CJ, Stern RA, Cantu RC, Geiling J, Blusztajn JK, Wolozin BL, Ikezu T, Stein TD, Budson AE, Kowall NW, Chargin D, Sharon A, Saman S, Hall GF, Moss WC, Cleveland RO, Tanzi RE, Stanton PK, McKee AC (2012) Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med 4(134):134ra60. doi: 10.1126/scitranslmed.3003716 source
- Not checked yetcites [91] Hof PR, Bouras C, Buee L, Delacourte A, Perl DP, Morrison JH (1992) Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer’s disease cases. Acta Neuropathol (Berl) 85(1):23–30 source
- Not checked yetcites [126] McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA (2009) Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 68(7):709–735. doi: 10.1097/NEN.0b013e3181a9d503 source
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The early and predominant involvement of PHF-tau pathology in the superior and dorsolateral frontal lobes in football players parallels the high frequency of impacts to the top of the head compared to those to the front, back, and side of the head in football [79], as well as fMRI data showing activation impairment in dorsolateral prefrontal cortex that is associated with significantly higher num”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
What the sources say
- Not checked yetcites [79] Guskiewicz KM, Mihalik JP, Shankar V, Marshall SW, Crowell DH, Oliaro SM, Ciocca MF, Hooker DN (2007) Measurement of head impacts in collegiate football players: relationship between head impact biomechanics and acute clinical outcome after concussion. Neurosurgery 61(6):1244–1252; discussion 1252–1243. doi: 10.1227/01.neu.0000306103.68635.1a source
- Not checked yetcites [180] Talavage TM, Nauman EA, Breedlove EL, Yoruk U, Dye AE, Morigaki KE, Feuer H, Leverenz LJ (2013) Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion. J Neurotrauma. doi: 10.1089/neu.2010.1512
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Rodent studies have shown that glucocorticoids and stress increase tau phosphorylation and cognitive deficits [75, 144, 173], and PHF-tau immunoreactivity in opiate user brains is significantly higher than in age-matched controls [4].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Phosphorylated tau pathology
What the sources say
- Not checked yetcites [75] Green KN, Billings LM, Roozendaal B, McGaugh JL, LaFerla FM (2006) Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer’s disease. J Neurosci 26(35):9047–9056. doi: 10.1523/JNEUROSCI.2797-06.2006 source
- Not checked yetcites [144] Okawa Y, Ishiguro K, Fujita SC (2003) Stress-induced hyperphosphorylation of tau in the mouse brain. FEBS Lett 535(1–3):183–189 source
- Not checked yetcites [173] Sotiropoulos I, Catania C, Riedemann T, Fry JP, Breen KC, Michaelidis TM, Almeida OF (2008) Glucocorticoids trigger Alzheimer disease-like pathobiochemistry in rat neuronal cells expressing human tau. J Neurochem 107(2):385–397. doi: 10.1111/j.1471-4159.2008.05613.x source
- Not checked yetcites [4] Anthony IC, Norrby KE, Dingwall T, Carnie FW, Millar T, Arango JC, Robertson R, Bell JE (2010) Predisposition to accelerated Alzheimer-related changes in the brains of human immunodeficiency virus negative opiate abusers. Brain 133(Pt 12):3685–3698. doi: 10.1093/brain/awq263 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Abnormal TDP-43 pathology is found in all stages of CTE. In early stages the inclusions consist of neuritic threads and dot-like inclusions in subpial, perivascular, and periventricular regions; cytoplasmic neuronal inclusions are first seen in Stage II disease and are characteristic of late stages where they partially co-localize with PHF-tau inclusions [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > TDP-43 pathology
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In our current experience of 103 neuropathologically confirmed cases of CTE, co-existent LBD was found in 12 (12 %) cases, MND in 13 (13 %), AD in 15 (15 %), and FTLD in 6 (6 %), suggesting that either repetitive trauma or the accumulation of tau pathology in CTE provokes the deposition of other abnormal proteins involved in neurodegeneration [127, 128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Chronic traumatic encephalopathy with co-morbid degenerative disease
What the sources say
- Not checked yetcites [127] McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, Perl DP, Hedley-Whyte ET, Price B, Sullivan C, Morin P, Lee HS, Kubilus CA, Daneshvar DH, Wulff M, Budson AE (2010) TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol. doi: 10.1097/NEN.0b013e3181ee7d85 source
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
hedgeddirectn = 103- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Some data suggests that trauma and athletic exposure are risk factors for developing ALS [30, 31, 166], although there are conflicting reports regarding single versus repetitive head injury [24].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > CTE with motor neuron disease
What the sources say
- Not checked yetcites [30] Chio A, Benzi G, Dossena M, Mutani R, Mora G (2005) Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 128(Pt 3):472–476. doi: 10.1093/brain/awh373 source
- Not checked yetcites [31] Chio A, Calvo A, Dossena M, Ghiglione P, Mutani R, Mora G (2009) ALS in Italian professional soccer players: the risk is still present and could be soccer-specific. Amyotroph Lateral Scler 10(4):205–209. doi: 10.1080/17482960902721634 source
- Not checked yetcites [166] Schmidt S, Kwee LC, Allen KD, Oddone EZ (2010) Association of ALS with head injury, cigarette smoking and APOE genotypes. J Neurol Sci 291(1–2):22–29. doi: 10.1016/j.jns.2010.01.011 source
- Not checked yetcites [24] Chen H, Richard M, Sandler DP, Umbach DM, Kamel F (2007) Head injury and amyotrophic lateral sclerosis. Am J Epidemiol 166(7):810–816. doi: 10.1093/aje/kwm153 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TDP-43 binds to many cellular transcripts including tau and alpha synuclein, and its dysregulation may underlie some of the pathologies seen with these proteins [162]. In particular, TDP-43 may influence tau iso-form expression [136].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > CTE as an acquired frontotemporal lobar degeneration
What the sources say
- Not checked yetcites [162] Sato T, Takeuchi S, Saito A, Ding W, Bamba H, Matsuura H, Hisa Y, Tooyama I, Urushitani M (2009) Axonal ligation induces transient redistribution of TDP-43 in brainstem motor neurons. Neuroscience 164(4):1565–1578. doi: 10.1016/j.neuroscience.2009.09.050 source
- Not checked yetcites [136] Morales R, Green KM, Soto C (2009) Cross currents in protein misfolding disorders: interactions and therapy. CNS Neurol Disord: Drug Targets 8(5):363–371 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TDP-43 is an RNA-binding protein that regulates RNA metabolism, including mRNA splicing, stability, and transport [167]. After acute traumatic injury in animal models, TDP-43 expression is upregulated and TDP-43 relocates from the neuronal nucleus to accumulate in the neuronal cytoplasm [134, 135]”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > CTE as an acquired frontotemporal lobar degeneration
What the sources say
- Not checked yetcites [167] Sephton CF, Cenik B, Cenik BK, Herz J, Yu G (2012) TDP-43 in central nervous system development and function: clues to TDP-43-associated neurodegeneration. Biol Chem 393(7):589–594. doi: 10.1515/hsz-2012-0115 source
- Not checked yetcites [134] Moisse K, Mepham J, Volkening K, Welch I, Hill T, Strong MJ (2009) Cytosolic TDP-43 expression following axotomy is associated with caspase 3 activation in NFL−/− mice: support for a role for TDP-43 in the physiological response to neuronal injury. Brain Res 1296:176–186. doi: 10.1016/j.brainres.2009.07.023 source
- Not checked yetcites [135] Moisse K, Volkening K, Leystra-Lantz C, Welch I, Hill T, Strong MJ (2009) Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res 1249:202–211. doi: 10.1016/j.brainres.2008.10.021 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In different autopsy series, the percentage of former professional American football players who have died and donated their brains to research varies from 50 % [88], 80 % [146], to 97 %) [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > American football
What the sources say
- Not checked yetcites [88] Hazrati LN, Tartaglia MC, Diamandis P, Davis KD, Green RE, Wennberg R, Wong JC, Ezerins L, Tator CH (2013) Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology. Frontiers Hum Neurosci 7:222. doi: 10.3389/fnhum.2013.00222 source
- Not checked yetcites [146] Omalu B, Bailes J, Hamilton RL, Kamboh MI, Hammers J, Case M, Fitzsimmons R (2011) Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery 69(1):173–183; discussion 183. doi: 10.1227/NEU.0b013e318212bc7b source
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Individuals who present with motor symptoms of MND have milder CTE at death (Stages II–III), a reflection of their shortened life span, whereas those who present with cognitive symptoms die with advanced CTE (Stage III and IV).”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > CTE with motor neuron disease
plaincorrelationaln = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“American football is the most common sport associated with CTE, accounting for more than half of reported cases; 75 % of reported football players with CTE played at the professional level.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > American football
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The sequence of neuropathological changes in CTE—first as a single focus and later as multiple perivascular foci of PHF-tau at the depths of the cerebral sulci—and their association with acute axonal injury and microbleeds suggest that an initial trauma may induce a focal change in PHF-tau and that continued exposure to repetitive trauma may induce multifocal, more widespread PHF-tau changes (Now”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Trauma exposure
What the sources say
- Not checked yetcites (Nowinski, personal communication)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The incidence and prevalence of CTE are not currently known and their precise determination will require longitudinal clinical studies and the capability to accurately diagnose CTE during life.”
§ The neuropathology of sport > Conclusion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“CTE has been reported most frequently in American football players and boxers, but players of other sports are also vulnerable, including those participating in ice hockey, professional wrestling, soccer, rugby, and baseball.”
§ The neuropathology of sport > Conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whether an isolated PHF-tau lesion advances to involve adjacent brain parenchyma may depend on additional factors, including age, gender, exposure to other toxins, and genetic susceptibilities.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Trauma exposure
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Resistance is perhaps understandable, as accepting trauma as the primary cause for CTE would have enormous financial repercussions, as well as necessitate major changes in the play or management of many popular sports and constitute a paradigm shift in the science of neurode-generation.”
§ The neuropathology of sport > Conclusion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“The progression of CTE from a multifocal state (Stage II) to widespread disease (Stage III) might represent a period of exponential increase in PHF-tau accumulation, hypothetically from such mechanisms as protein templating or other modes of interneuronal spreading [128].”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Trauma exposure
What the sources say
- Not checked yetcites [128] McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64. doi: 10.1093/brain/aws307 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Nonetheless, the play of sports is also associated with some risks, including risks for TBI, catastrophic traumatic injury and death.”
§ The neuropathology of sport > Conclusion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three of the hockey players were enforcers, which likely contributed to their overall exposure to repetitive brain trauma.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Ice hockey
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is also growing awareness that repetitive minor TBIs may lead to persistent cognitive, behavioral, and psychiatric problems and, rarely, to the development of CTE.”
§ The neuropathology of sport > Conclusion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is possible, even likely, that some individuals develop a single isolated focus of PHF-tau that never progresses.”
§ The neuropathology of sport > Adverse neuropathological outcomes associated with sports participation > Trauma exposure
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The 117 athletes in the mTBI brain bank are representative of athletes who sustain concussions, so neuropathological findings in them can be generalized to concussion pathology in athletes.
“Over the last 5 years, 117 brains of athletes, defined as a player over the age of 12 years who participated in organized sports for at least 3 consecutive years, have been analyzed at the mTBI brain bank at VA Boston/Boston University School of Medicine.”
The paper relies on this without support.
Self-reported concussion history in retired players accurately reflects exposure to repetitive brain trauma.
“surveys of retired professional football players found that players who reported sustaining three or more concussions were significantly more likely to report cognitive symptoms, including a threefold increase in self-reported significant memory impairment and a fivefold increase in diagnosed mild cognitive impairment [77].”
The paper relies on this without support.
The provisional pathological diagnostic criteria and four-stage staging system for CTE are valid for classifying the cases described.
“Provisional criteria for the pathological diagnosis of CTE and four pathological stages of severity have been proposed based on the topography of PHF-tau pathology [128]; formal consensus validation of these diagnostic and staging criteria by a large group of neuropathologists is currently in progress”
The paper relies on this without support.
The autopsy series of neuropathologically confirmed CTE cases is representative enough to estimate co-occurrence, clinical features, and mortality patterns.
“In our current experience of 103 neuropathologically confirmed cases of CTE, co-existent LBD was found in 12 (12 %) cases, MND in 13 (13 %), AD in 15 (15 %), and FTLD in 6 (6 %)”
The paper relies on this without support.
The clinical symptoms reported in subjects with each CTE stage are attributable to the CTE pathology rather than to other causes.
“Symptoms in Stage II CTE are variable, but in some instances there are prominent behavioral and personality changes, paranoia, irritability, depression, headaches, and short-term memory loss.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In conclusion, the prevailing theory of CTE, often expressed in articles as fact, is that it is a distinct (1, 3, 9-11) and unique (10) neurodegenerative disease (9-13).”
From Mild Chronic Traumatic Encephalopathy Neuropathology in People With No Known Participation in Contact Sports or History of Repetitive Neurotrauma (2019) · cites this paper as [13]
Citations
Cites
Items 201–205 of 205
Exercise to Enhance Neurocognitive Function After Traumatic Brain Injury
Fogelman, D. R., & ZAFONTE, R. D. (2012) · PM&R · doi:10.1016/j.pmrj.2012.09.028 · Cited by 28
López‐González, I., Carmona, M., Blanco, R., Luna‐Muñoz, J., Martínez‐Mandonado, A., Mena, R., & Ferrer, I. (2013) · Brain Pathology · doi:10.1111/j.1750-3639.2012.00627.x · Cited by 28
Acute on Chronic Subdural Hematoma in a Female Boxer: A Case Report
MIELE, V. J., CARSON, L., CARR, A., & BAILES, J. E. (2004) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000145470.16938.7a · Cited by 24
Exercise, Depression, and Cognition
Bartholomew, J. B., & Ciccolo, J. T. (2008) · Human Kinetics eBooks · doi:10.5040/9781492597315.ch-003 · Cited by 16
Cantu, R. C., Herring, S. A., & Putukian, M. (2007) · New England Journal of Medicine · doi:10.1056/nejmc070289 · Cited by 9
Cited by
Sorted by citations
Weıntraub, S. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530120075013 · Cited by 3,018
The neuropathology of traumatic brain injury
McKee, A. C., & Daneshvar, D. H. (2015) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52892-6.00004-0 · Cited by 899
Self-citationthe TBI/CTE group, McKee, A. C., Cairns, N. J., Dickson, D. W., Folkerth, R. D., Dirk Keene, C., Litvan, I., Perl, D. P., Stein, T. D., Vonsattel, J.-P., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1515-z · Cited by 885
Self-citationNeuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.010 · Cited by 799
Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules
Falcon, B., Zivanov, J., Zhang, W., Murzin, A. G., Garringer, H. J., Vidal, R., Crowther, R. A., Newell, K. L., Ghetti, B. F., Goedert, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1026-5 · Cited by 722
Metadata
- Authors
- McKee, A. C., Daneshvar, D. H., Alvarez, V. E., & Stein, T. D.
- Affiliations
- VA Boston Healthcare System (US)
- Boston University (US)
- Corresponding author
- McKee, Ann C.
- Venue
- Acta Neuropathologica
- Published
- 2013-12-24
- Volume
- 127
- Issue
- 1
- Pages
- 29-51
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC4255282
- OpenAlex
- W2162142017
- Cited by
- 422
- References
- 205
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 29 · 2023: 38 · 2022: 40 · 2021: 32 · 2020: 32 · 2019: 40 · 2018: 33 · 2017: 40 · 2016: 36 · 2015: 53 · 2014: 13
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX001038)
- U.S. Public Health Service (0572063345-5)
- National Institute on Aging (R01AG1649, P30AG013846, P30-AG13846))
- National Institute of Neurological Disorders and Stroke (U01NS086659)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports injuries and prevention
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Physical Activity and Health
- Keywords
- chronic traumatic encephalopathy, concussion, mild traumatic brain injury, second impact syndrome, neurodegeneration, TDP-43, sports-related brain injury, cognitive impairment, executive dysfunction, American football, boxing
- MeSH terms
- Animals, Athletic Injuries, Brain, Brain Injuries, Cognition, Humans, Sports
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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