The DOI matches its Crossref record; 74 of the 76 references it cites were found in a registry or an index; 12 of the 62 sources its claims cite were checked for support.
Association of ALS with head injury, cigarette smoking and APOE genotypes
Open accessAbstract
Objective An increased risk of ALS has been reported for US veterans, but the cause is unknown. Since head injury and cigarette smoking are two previously implicated environmental risk factors that are more common in military than civilian study populations, we tested their association with ALS in a US veteran study population.Methods We used logistic regression to examine the association of ALS with head injury and cigarette smoking in 241 incident cases and 597 controls. Since APOE is a plausible ALS candidate gene, we also tested its main effect and its statistical interaction with these environmental exposures.Results Cigarette smoking was not associated with ALS in this predominantly male and Caucasian population. Veterans who had experienced head injuries during the last 15years before the reference date had an adjusted odds ratio of 2.33 (95% confidence interval 1.18-4.61), relative to veterans without any head injuries. This association was strongest in APOE-4 carriers.Conclusions Our results add to the body of evidence suggesting that head injuries may be a risk factor for multiple neurodegenerative diseases, including ALS. We hypothesize that the strength of association between head injuries and ALS may depend upon APOE genotype.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In a US veteran case-control study, cigarette smoking was not associated with ALS, but head injury within the 15 years before the reference date was associated with higher ALS odds. The head-injury association appeared strongest among APOE-4 carriers, though the authors call for replication.
Key findings
- Among 241 incident ALS cases and 597 controls, cigarette smoking was not associated with ALS, including analyses by never/former/current status, smoking duration, and pack-years.
- Veterans with head injury in the last 15 years before the reference date had adjusted OR 2.33 (95% CI 1.18–4.61) for ALS relative to no head injuries.
- The head-injury association was strongest in APOE-4 carriers: genotype-specific OR for injury within ≤15 years was 7.5 (95% CI 1.4–41.3) in APOE-4 carriers, versus 1.9 (0.8–4.4) in APOE 3/3 and 2.2 (0.8–5.6) in APOE-2 carriers.
- APOE-2 carriage showed a non-significant elevated ALS risk (OR 1.32, 95% CI 0.88–1.98); APOE-4 carriage was not associated with ALS risk.
Methods
- Case-control study within the GENEVA study of US veterans: 241 incident sporadic ALS cases with interviews and 597 veteran controls; APOE genotypes were available for 417 cases and 482 controls.
- Structured telephone interviews assessed head injury and cigarette smoking; APOE genotypes were determined from rs7412 and rs429358.
- Unconditional logistic regression estimated ALS associations adjusted for age, sex, race/ethnicity, and education, with gene-environment interaction tests between APOE, smoking, and head-injury interval.
Limitations
- The authors state the study is not population-based, case and control enrollment methods were not identical, and case enrollment may have increased the proportion of more slowly progressing individuals.
- The authors note control participation was 41%, they lacked detailed context/severity of head injuries, and genotype-specific categories were limited with wide confidence intervals requiring replication.
- Evident from the text: the sample was predominantly male and Caucasian veterans, so generalizability to other populations is limited; exposure and injury data were self-reported, and the observational design cannot establish causality.
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Claims the paper makes
31 Own result · 28 Own method · 20 No full text of the sources · 13 Own interpretation · 6 Supported so far · 4 Supported · 2 Partly supported · 1 No basis given · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Consistent with previous epidemiologic studies of head injury in PD (55;56) and ALS (21), our data also support the existence of a relatively long period of latency between injury and ALS onset, since head injuries up to 15 years before the reference date contributed to the observed increased odds of ALS.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [55] Bower, 2003, Head trauma preceding PD: a case–control study, Neurology source
- Not checked — no full text of the sourcecites [56] Goldman, 2006, Head injury and Parkinson's disease risk in twins, Ann Neurol source
- Supportedcites [21] Chen, 2007, Head injury and amyotrophic lateral sclerosis, Am J Epidemiol source
Citation (21) identifies a previous epidemiologic study of head injury and ALS; the 15-year latency finding is explicitly attributed to the citing authors’ own data. The cited paper’s results (p. 811) report an association between recent or repeated head injuries and higher ALS risk. (LLM, conf=0.93)
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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The same study also estimated a pooled OR of 1.7 (95% CI 1.3–2.2) for at least one previous head injury, based on a meta-analysis of eight ALS studies.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Supportedcites [21] Chen, 2007, Head injury and amyotrophic lateral sclerosis, Am J Epidemiol source
The Statistical analysis section says the authors identified eight earlier papers, excluded one, and included their current study, yielding eight studies in the meta-analysis. The results section (p. 811) reports a 1.7-fold higher ALS risk among people with head injuries than among those without, with a 95% CI of 1.3–2.2. (LLM, conf=0.93)
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.
- Supported
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
“Similarly, ALS was not significantly associated with smoking duration and cigarette pack-years.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with Cigarette Smoking
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: Excluding smoking data reported within the last two years before the reference date is sufficient to remove smoking changes caused by early ALS symptoms.
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 no association between ALS and cigarette smoking, analyzed as never vs. former vs. current smoking.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with Cigarette Smoking
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.
- Rests on an assumption: Excluding smoking data reported within the last two years before the reference date is sufficient to remove smoking changes caused by early ALS symptoms.
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
“Cigarette smoking was not associated with ALS in this predominantly male and Caucasian population.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > Abstract > Results
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.
- Rests on an assumption: Excluding smoking data reported within the last two years before the reference date is sufficient to remove smoking changes caused by early ALS symptoms.
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
“a higher proportion (55% vs. 34%) had received imminent danger pay for active duty status in an area that presented an imminent danger of being exposed to hostile fire or explosion of hostile mines”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
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.
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
“Carriage of the APOE-4 allele was not associated with ALS risk.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with APOE Genotypes
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.
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
“The inclusion of all possible pairwise interaction terms for these variables did not lead to a significant improvement in model fit.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Gene-Environment (GxE) Interaction Analysis
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.
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
“A stronger association was observed with the interval between the last injury and the reference date, with an OR of 2.09 (95% CI 1.23–3.57) for the first quartile (<=24 years).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with Head Injury
boostedcorrelational- 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: Excluding head injuries reported within two years of the reference date is sufficient to remove injuries caused by early ALS symptoms.
- Rests on an assumption: The association between head injury and ALS is not due to unmeasured confounding.
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
“This result was similar when all injuries reported by the participants, not just the last injury, were evaluated.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with Head Injury
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. 41
- It may state two separate claims as one. 26
- The quote only partly states this claim. 1
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“As expected, the prevalence of both cigarette smoking and head injuries was higher in GENEVA controls than in population-based studies of civilian controls of similar age (ever vs. never smoking: 64.2% vs. 53.4% in (4); at least one head injury: 31.0% vs. 16.4% in (21)).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Clinical, Demographic and Exposure Frequency Information
What the sources say
- Not checked — no full text of the sourcecites [4] Nelson, 2000, Population-based case–control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption, Am J Epidemiol source
- Supportedcites [21] Chen, 2007, Head injury and amyotrophic lateral sclerosis, Am J Epidemiol source
The citation to Chen et al. is attached to the head-injury comparison, not the smoking comparison, which cites a different source. Table 2 (p. 813) reports that 12.5% of controls had one head injury and 3.9% had more than one, totaling the cited 16.4%. (LLM, conf=0.90)
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. It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“several studies have suggested that this association may be stronger in carriers of the APOE-4 allele (30–32).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > INTRODUCTION
What the sources say
- Supportedcites [30] Mayeux, 1995, Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer's disease, Neurology source
The Results report a higher odds ratio for Alzheimer’s disease when head injury and APOE-ε4 occur together than for either factor alone. The Discussion describes this as a tentative suggestion of synergy, consistent with the citing sentence’s hedged wording. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [31] Katzman, 1996, Apolipoprotein-epsilon4 and head trauma: synergistic or additive risks?, Neurology
- Not checked — no full text of the sourcecites [32] Plassman, 2000, Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias, Neurology source
hedgedcorrelational- 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.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“and head injuries (14;20–22).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [14] Deapen, 1986, A case–control study of amyotrophic lateral sclerosis, Am J Epidemiol source
- Not checked — no full text of the sourcecites [20] Kondo, 1981, Case–control studies of motor neuron disease: association with mechanical injuries, Arch Neurol source
- Supportedcites [21] Chen, 2007, Head injury and amyotrophic lateral sclerosis, Am J Epidemiol source
The Head Injury and ALS section (p. 811) reports a significant association in its meta-analysis between head injury and ALS risk. It also reports higher risk with repeated or recent head injuries in the paper’s case-control study, supporting the broad claim of a previous association. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [22] Binazzi, 2008, An exploratory case–control study on spinal and bulbar forms of amyotrophic lateral sclerosis in the province of Rome, Amyotroph Lateral Scler source
plaincorrelational- 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 cited sources support only part of this claim — read each source’s verdict below.
In the paper
“and possibly a worse prognosis following an ALS diagnosis (34–37).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > INTRODUCTION
What the sources say
- Partly supportedcites [34] Al-Chalabi, 1996, Association of apolipoprotein E ε4 allele with bulbar-onset motor neuron disease, Lancet sourceExperimental — accuracy not yet measured
The Results report shorter median survival for ε4 carriers than noncarriers (35 versus 49 months), which is consistent with the claim’s cautious wording. But the difference was not statistically significant, and the analysis controlling for gender, bulbar onset, and age of onset found no significant association with survival. The paper therefore does not establish worse prognosis following diagnosis. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [35] Moulard, 1996, Apolipoprotein E genotyping in sporadic amyotrophic lateral sclerosis: evidence for a major influence on the clinical presentation and prognosis, J Neurol Sci source
- Not checked — no full text of the sourcecites [36] Smith, 1996, Apolipoprotein E epsilon 4 in bulbar-onset motor neuron disease, Lancet source
- Not checked — no full text of the sourcecites [37] Li, 2004, Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis, Neurogenetics 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“it is well within the range reported by several population-based studies, which extends from 16 months (65;66) to 28 months (67), with most studies reporting values between 19 and 23 months (68–70).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [65] O'Toole, 2008, Epidemiology and clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004, J Neurol Neurosurg Psychiatry source
- Not checked — no full text of the sourcecites [66] Zoccolella, 2008, Analysis of survival and prognostic factors in amyotrophic lateral sclerosis: a population based study, J Neurol Neurosurg Psychiatry source
- Partly supportedcites [67] Kamel, 2008, Association of lead exposure with survival in amyotrophic lateral sclerosis, Environ Health Perspect sourceExperimental — accuracy not yet measured
The Results report a median survival of 28 months from diagnosis to death, supporting the value attributed to this source. But the Materials and Methods say cases were recruited from two ALS clinics, and the Discussion describes them as drawn from tertiary care centers, so this was not a population-based study. The 16-month and 19–23-month values are attributed to other citations. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [68] Sorenson, 2002, Amyotrophic lateral sclerosis in Olmsted County, Minnesota, 1925 to 1998, Neurology source
- Not checked — no full text of the sourcecites [69] Chio, 2002, Early symptom progression rate is related to ALS outcome: a prospective population-based study, Neurology source
- Not checked — no full text of the sourcecites [70] del Aguila, 2003, Prognosis in amyotrophic lateral sclerosis: a population-based study, Neurology source
boosted- 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 sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The latter category includes professional or intense recreational soccer playing, which has been associated with ALS in some reports (17;50).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Supportedcites [17] Chio, 2005, Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players, Brain source
The Abstract reports an elevated ALS standardized morbidity ratio among Italian male professional football players, and the Discussion describes a significant relationship with playing professional football. This supports the professional-soccer part of the sentence; the paper does not need to establish the separate recreational-soccer alternative attributed alongside another citation. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [50] Chio, 2008, Amyotrophic lateral sclerosis and soccer: a different epidemiological approach strengthen the previous findings, J Neurol Sci source
hedgedcorrelational- 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Our results are consistent with a recently reported trend for an increasing ALS association with a decreasing number of years between the last head injury and ALS diagnosis, and with an increasing age at the last injury (21).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Supportedcites [21] Chen, 2007, Head injury and amyotrophic lateral sclerosis, Am J Epidemiol source
Table 2 (p. 813) shows higher ALS odds ratios as the time since the last head injury decreases: 0.9 for more than 30 years, 1.2 for 11–30 years, and 3.2 for the most recent category. Its age-at-last-injury rows also rise from 1.1 for injuries before age 30 to 1.4 for injuries at ages 30–40. These results support the citing sentence’s description of trends, without establishing that each category differs significantly. (LLM, conf=0.86)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“a previous study reported that ALS patients were approximately twice as likely as controls to have always been slim or to have been varsity athletes (19).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Supportedcites [19] Scarmeas, 2002, Premorbid weight, body mass, and varsity athletics in ALS, Neurology source
The Results (p. 1) report that patients with motor neuron disease were more likely than controls to have always been slim or to have been varsity athletes. The adjusted odds ratios were 2.10 and 1.89, respectively—approximately twice the odds for each characteristic. (LLM, conf=0.93)
hedgedcorrelational- 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. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In that study, the strongest association was observed for the interval “<=10 years between last injury and diagnosis” (OR 3.2, 95% CI 1.0–10.2), with a slightly elevated risk for the interval 11–30 years.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Supportedcites [21] Chen, 2007, Head injury and amyotrophic lateral sclerosis, Am J Epidemiol source
Table 2 (p. 813) reports the highest odds ratio in the years-since-last-head-injury categories for injury within 10 years: 3.2 (95% CI 1.0–10.2). The 11–30-year category has a slightly elevated odds ratio of 1.2. The Results (p. 811) also describes the within-10-years finding. (LLM, conf=0.93)
plaincorrelational- 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. It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Synergistic effects of head injury and APOE genotypes in AD were reported by some (30–32), but not all studies (53;54).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Supportedcites [30] Mayeux, 1995, Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer's disease, Neurology source
The Results report that the joint association of head injury and APOE-ε4 with Alzheimer’s disease exceeded the associations expected from either factor alone, suggesting synergy. The Discussion calls the conclusion tentative because the formal interaction test was not statistically significant. This source supports the sentence’s “some studies” portion; the “not all” portion is assigned to other citations. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [31] Katzman, 1996, Apolipoprotein-epsilon4 and head trauma: synergistic or additive risks?, Neurology
- Not checked — no full text of the sourcecites [32] Plassman, 2000, Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias, Neurology source
- Not checked — no full text of the sourcecites [53] O'Meara, 1997, Head injury and risk of Alzheimer's disease by apolipoprotein E genotype, Am J Epidemiol source
- Not checked — no full text of the sourcecites [54] Mehta, 1999, Head trauma and risk of dementia and Alzheimer's disease: the Rotterdam Study, Neurology source
plaincorrelational- 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. It may state two separate claims as one.
- Supported
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
“Restricting the analysis to non-Hispanic Caucasian subjects generated slightly lower ORs (data not shown).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with APOE Genotypes
plaincorrelational- 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 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
“Figure 1 shows that more ALS cases than controls experienced head injuries during the last 15 years preceding the reference date, while intervals of the more distant past contained similar proportions of cases and controls, and controls somewhat outweighed cases for injuries reported more than 40 years ago.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with Head Injury
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: Excluding head injuries reported within two years of the reference date is sufficient to remove injuries caused by early ALS symptoms.
- Rests on an assumption: The association between head injury and ALS is not due to unmeasured confounding.
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
“Being a carrier of the APOE-2 allele was associated with a slightly elevated ALS risk, compared to homozygous carriers of the APOE-3 allele (OR 1.32, 95% CI 0.88–1.98), but this result did not reach statistical significance.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with APOE Genotypes
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.
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
“Our predominantly male and Caucasian study population of US veterans has a higher head injury and smoking prevalence than comparable civilian cohorts and a larger sample size than most previous studies of ALS and environmental risk factors.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
plaincorrelational- 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. 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
“Of the cases included in this analysis, 46.5% were identified as potential Registry participants through a search of VA databases, while 53.5% were enrolled solely via self-referral.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with Head Injury
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. 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
“there was weak evidence for gene-environment interaction, since the association between ALS and the head injury variable was stronger in APOE-4 carriers (LRT 2.7 on 1 df, p=0.10) than in APOE-2 carriers (LRT 0.2 on 1 df, p=0.68).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Gene-Environment (GxE) Interaction Analysis
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.
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
“The ORs and 95% CIs for the first three intervals shown in Figure 1 were 1.62 (0.52, 5.08), 2.28 (0.59, 8.88) and 3.24 (1.15, 9.12), respectively.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Association of ALS with Head Injury
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: Excluding head injuries reported within two years of the reference date is sufficient to remove injuries caused by early ALS symptoms.
- Rests on an assumption: The association between head injury and ALS is not due to unmeasured confounding.
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
“This association was strongest in APOE-4 carriers.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > Abstract > Results
boostedcorrelational- 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. The quote only partly states this claim.
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
“the global tests of “main effect plus interaction” indicated that the head injury variable had the greatest impact on the model fit (likelihood ratio test (LRT) 12.2 on 8 df), followed by APOE genotypes (LRT 8.8 on 8 df).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Gene-Environment (GxE) Interaction Analysis
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.
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
“The 1 df test of interaction was slightly more significant when the sample was restricted to non-Hispanic Caucasians, but the confidence intervals for the genotype-specific ORs were approximately twice as wide due to a smaller sample size.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Gene-Environment (GxE) Interaction Analysis
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“to account for the fact that ALS cases may stop smoking due to early signs of the disease, smoking data (duration, dose) reported within the last two years before the reference date were excluded and smoking status (former vs. current) was determined based on the reference date minus two years.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Definition of Analysis Variables
plainn = 17- 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.
- Rests on an assumption: Excluding smoking data reported within the last two years before the reference date is sufficient to remove smoking changes caused by early ALS symptoms.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“At the time of this analysis, 41% of eligible controls had consented to participate, which is a slightly higher rate than the 36% reported by the Millennium Cohort Study (42), and within the range reported for contemporary population-based case-control studies (43).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Study Population
What the sources say
- Not checked — no full text of the sourcecites [42] Ryan, 2007, Millennium cohort: enrollment begins a 21-year contribution to understanding the impact of military service, J Clin Epidemiol source
- Not checked — no full text of the sourcecites [43] Morton, 2006, Reporting participation in epidemiologic studies: a survey of practice, Am J Epidemiol 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. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Unconditional logistic regression (SAS Institute Inc., Cary, NC) was used to estimate associations of ALS with the variables of interest, adjusted for age, sex, race/ethnicity and education.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Statistical Methods
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.
- Rests on an assumption: The association between head injury and ALS is not due to unmeasured confounding.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“An attempt was made to frequency-match cases and controls on age (5-year age groups, using age at ALS diagnosis for cases and age at interview for controls), gender, and use of VA health care”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Study Population
hedged- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We performed a sensitivity analysis to examine whether the results were consistent regardless of whether PMA patients were included or excluded.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Study Population
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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Following reports of a potentially increased risk of ALS in US veterans (23–25), we are currently conducting a case-control study called GENEVA”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [23] Horner, 2003, Occurrence of amyotrophic lateral sclerosis among Gulf War veterans, Neurology source
- Not checked — no full text of the sourcecites [24] Haley, 2003, Excess incidence of ALS in young Gulf War veterans, Neurology source
- Not checked — no full text of the sourcecites [25] Weisskopf, 2005, Prospective study of military service and mortality from ALS, Neurology source
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.
In the paper
“A prospective study based on ALS mortality data found that an association with cigarette smoking was restricted to women (5).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [5] Weisskopf, 2004, Prospective study of cigarette smoking and amyotrophic lateral sclerosis, Am J Epidemiol source
plaincorrelational- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A telephone screener was used to verify the absence of ALS and other neurological disorders.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Study Population
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The GENEVA study was conducted in accordance with the Declaration of Helsinki of the World Medical Association, and was approved by the Institutional Review Boards of the Durham VA and Duke University Medical Centers. All study participants provided informed consent.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Study Population
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. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“APOE genotypes were in Hardy-Weinberg equilibrium in both cases and controls; their frequencies (Table 4) were similar to previous reports for the relevant age groups (44;47;48).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Clinical, Demographic and Exposure Frequency Information
What the sources say
- Not checked — no full text of the sourcecites [44] Bennet, 2007, Association of apolipoprotein E genotypes with lipid levels and coronary risk, JAMA source
- Not checked — no full text of the sourcecites [47] Farrer, 1997, Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium, JAMA source
- Not checked — no full text of the sourcecites [48] Song, 2004, Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease, Ann Intern Med 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“the patient’s diagnosis recorded by the Registry was based on medical record reviews conducted by six neurologists with particular expertise in ALS, who used the El Escorial criteria for definite, probable or possible ALS.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Study Population
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All frequency distributions were very similar when the sample was restricted to non-Hispanic Caucasian cases and controls.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > RESULTS > Clinical, Demographic and Exposure Frequency Information
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.
In the paper
“Carriers of the APOE-4 allele may have an earlier age at onset of Parkinson’s disease (33)”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [33] Li, 2004, Apolipoprotein E controls the risk and age at onset of Parkinson disease, Neurology 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we restricted the analysis to ALS patients who agreed to participate in the Registry within 12 months of diagnosis and did not report a first-degree family history of ALS”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Study Population
plainn = 241- 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.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Environmental factors that have previously been associated with ALS risk include cigarette smoking (3–5)”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [3] Kamel, 1999, Association of cigarette smoking with amyotrophic lateral sclerosis, Neuroepidemiology source
- Not checked — no full text of the sourcecites [4] Nelson, 2000, Population-based case–control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption, Am J Epidemiol source
- Not checked — no full text of the sourcecites [5] Weisskopf, 2004, Prospective study of cigarette smoking and amyotrophic lateral sclerosis, Am J Epidemiol source
plaincorrelational- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To reduce recall bias, and to account for the fact that injuries reported by ALS cases may be due to early signs of muscle weakness, any head injuries reported within two years of the reference date were excluded.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Definition of Analysis Variables
plaindirectn = 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.
Probably not a substantial claim. It may state two separate claims as one.
- Rests on an assumption: Excluding head injuries reported within two years of the reference date is sufficient to remove injuries caused by early ALS symptoms.
In the paper
“our analysis dataset included PMA patients, who typically experience a similarly progressive disease course (n=37 with interviews; n=66 with DNA samples), while PLS patients, who typically progress much more slowly (41), were excluded.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Study Population
What the sources say
- Not checked — no full text of the sourcecites [41] Tartaglia, 2007, Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis: examination of symptoms and signs at disease onset and during follow-up, Arch Neurol source
plainn = 37- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We required 95% genotyping efficiency and matching genotypes of quality control samples within and across all plates in order to include samples in the statistical analysis.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > MATERIAL AND METHODS > Genotyping Methods
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. It may state two separate claims as one.
In the paper
“It is well known that the APOE-4 (ε4) allele is a strong risk factor for AD (29).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [29] Corder, 1993, Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families, Science source
boostedcorrelational- 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
“they may more likely be experienced by individuals with a lifetime history of vigorous physical activity.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
hedgedcorrelational- 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.
In the paper
“A study of 93 twin pairs who were discordant for PD replicated this association with a similarly large effect size (OR 3.8, 95% CI 1.3–11.0) (56).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [56] Goldman, 2006, Head injury and Parkinson's disease risk in twins, Ann Neurol source
plaincorrelational- 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.
In the paper
“Our observed statistical association supports a continued evaluation of apoe as a potential “injury-response” protein in experimental studies of motor neuron degeneration (62).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [62] Haasdijk, 2002, Increased apolipoprotein E expression correlates with the onset of neuronal degeneration in the spinal cord of G93A-SOD1 mice, Neurosci Lett source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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 be too vague to check against evidence.
In the paper
“and supported an earlier hypothesis that this effect may be restricted to males (52).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [52] Mortimer, 1985, Head injury as a risk factor for Alzheimer's disease, Neurology 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“An additional study limitation is that we did not query participants about the context of the reported head injuries and do not have access to more detailed medical or military records about the nature and severity of these injuries.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
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.
In the paper
“In a population-based study of PD, an OR of 4.3 (95% CI 1.2–15.2) was reported for head injuries leading to loss of consciousness or hospitalization, as documented in medical records (55).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [55] Bower, 2003, Head trauma preceding PD: a case–control study, Neurology source
plaincorrelational- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Strengths of our study include its relatively large sample size”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“that the case enrollment methods may have increased the proportion of more slowly progressing individuals in the analysis sample.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
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.
In the paper
“As previously discussed (56), there are multiple biological mechanisms by which head injuries may trigger the molecular pathways leading to neuronal degeneration.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [56] Goldman, 2006, Head injury and Parkinson's disease risk in twins, Ann Neurol 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.
In the paper
“A meta-analysis of 15 studies yielded an estimated OR for AD of 1.6 (95% CI 1.2–2.1) due to ever having sustained a head injury with loss of consciousness (51)”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [51] Fleminger, 2003, Head injury as a risk factor for Alzheimer's disease: the evidence 10years on; a partial replication, J Neurol Neurosurg Psychiatry source
hedgedcorrelational- 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.
In the paper
“modifying effects of the different apoe protein isoforms on these pathways are biologically plausible and have been evaluated in experimental model systems (61).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [61] Crawford, 2009, Apolipoprotein E-genotype dependent hippocampal and cortical responses to traumatic brain injury, Neuroscience source
plainconditional- 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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“They range from inflammatory and glutamate excitotoxicity pathways (57;58), which increase the metabolic demands of neurons and microglia, to oxidative stress pathways that may impact mitochondrial function (59).”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [57] Lenzlinger, 2001, The duality of the inflammatory response to traumatic brain injury, Mol Neurobiol source
- Not checked — no full text of the sourcecites [58] Arundine, 2004, Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury, Cell Mol Life Sci source
- Not checked — no full text of the sourcecites [59] Frantseva, 2002, Neurotrauma/neurodegeneration and mitochondrial dysfunction, Prog Brain Res 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. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the control participation rate of 41% is less than ideal”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
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.
In the paper
“While the risk of head injuries is generally twice as high in men as in women (49)”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [49] Langlois, 2003, Traumatic brain injury-related hospital discharges. Results from a 14-state surveillance system, 1997, MMWR Surveill Summ
plaincorrelational- 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
“several specific attributes of the GENEVA study population, beyond its high proportion of men, may contribute to the higher prevalence of head injuries.”
§ Association of ALS with Head Injury, Cigarette Smoking and APOE Genotypes > DISCUSSION
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 relies on this without support.
Excluding head injuries reported within two years of the reference date is sufficient to remove injuries caused by early ALS symptoms.
“To reduce recall bias, and to account for the fact that injuries reported by ALS cases may be due to early signs of muscle weakness, any head injuries reported within two years of the reference date were excluded.”
The paper relies on this without support.
The association between head injury and ALS is not due to unmeasured confounding.
“All results were adjusted for age, sex, race/ethnicity and education.”
The paper relies on this without support.
Excluding smoking data reported within the last two years before the reference date is sufficient to remove smoking changes caused by early ALS symptoms.
“to account for the fact that ALS cases may stop smoking due to early signs of the disease, smoking data (duration, dose) reported within the last two years before the reference date were excluded”
The paper relies on this without support.
Most previous studies of ALS and head injury did not include a more detailed analysis of the injury-to-onset interval or the age at which head injuries occurred.
“Most previous studies of ALS and head injury did not include a more detailed analysis of the injury-to-onset interval or the age at which head injuries occurred.”
The paper relies on this without support.
None of the studies conducted to date examined APOE genotypes jointly with head injuries.
“None of the studies conducted to date examined APOE genotypes jointly with head injuries.”
The paper relies on this without support.
The success of GWAS in ALS has been much more limited than for other complex human diseases.
“the success of GWAS in ALS has been much more limited than for other complex human diseases.”
The paper relies on this without support.
Environmental risk factors have been completely ignored in all of the ALS GWAS studies published to date.
“environmental risk factors, which have been completely ignored in all of the ALS GWAS studies published to date.”
The paper relies on this without support.
Recall bias would lead to under-reporting of milder injuries by controls.
“which would be expected to lead to under-reporting of milder injuries by controls.”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, in a veteran cohort, those with head injury, especially head injuries within 15 years prior to diagnosis, were found to be significantly more likely to have developed ALS (16).”
From Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort (2018) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Some studies have reported that multiple head injuries and age at first head injury were associated with ALS, which is also consistent with the findings we observed in our study [18,20,61,62].”
From Head Injury and Amyotrophic Lateral Sclerosis: Population-Based Study from the National ALS Registry (2025) · cites this paper as [18]
Experimental — accuracy not yet measuredIn the citing 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].”
From The neuropathology of sport (2014) · cites this paper as [166]
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Metadata
- Authors
- Schmidt, S., Kwee, L. C., Allen, K. D., & Oddone, E. Z.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- Schmidt, Silke
- Venue
- Journal of the Neurological Sciences
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 291
- Issue
- 1-2
- Pages
- 22-29
- ISSN
- 0022-510X (ISSN-L)
- PMC
- PMC2840700
- OpenAlex
- W1988832005
- Semantic Scholar
- e9ed91a7ef1637a4dac73b42f33a0a92f4b69671
- Cited by
- 117
- References
- 76
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 10 · 2015: 13 · 2014: 14 · 2013: 6 · 2012: 15
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the Neurological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (R01ES013244)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- amyotrophic lateral sclerosis, traumatic brain injury, cigarette smoking, APOE genotype, APOE ε4, veterans, environmental risk factors, gene-environment interaction, neurodegenerative diseases
- MeSH terms
- Amyotrophic Lateral Sclerosis, Apolipoproteins E, Environmental Exposure, Female, Genotype, Craniocerebral Trauma, Heterozygote, Humans, Male, Middle Aged, Risk Factors, Smoking, United States, Veterans, Logistic Models, Odds Ratio, Genetic Predisposition to Disease, White People, Apolipoprotein E4
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