Can mild traumatic brain injury alter cognition chronically? A LIMBIC-CENC multicenter study.

May combine two claims.

Objective, late cognitive deficits after mTBI have been elusive to document at the group level, with multiple meta-analytic reviews concluding insufficient evidence for deleterious effects of mTBI on objective cognitive assessment beyond the first few months post-injury.

“In general, objective, late cognitive deficits after mTBI have been elusive to document at the group level, with multiple, meta-analytic reviews concluding insufficient evidence for deleterious effects of mTBI on objective cognitive assessment beyond the first few months post-injury”

• cites Belanger et al., 2005 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites Binder et al., 1997 sourceNot checked — no full text of the source
• cites Frencham et al., 2005 sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

There is emerging evidence that repeated mTBI may confer additional risk for both persisting symptoms and cognitive compromise.

“There is emerging evidence that repeated mTBI may confer additional risk for both persisting symptoms and cognitive compromise.”

• cites Guskiewicz et al., 2003 sourceNot checked — no full text of the source
• cites Manley et al., 2017 sourceSupported
• cites Bachstetter et al., 2020 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The strength of correlation between the seven cognitive domains within the sample was generally moderate, with values ranging from r=0.19 to r=0.49.

“The strength of correlation between the seven cognitive domains within our sample was generally in the ‘moderate’ range (Cohen, 1988), with values ranging from r=0.19 to r=0.49 (full results are available online in Supplemental Table S1).”

• cites Cohen, 1988 sourceCould not verify

  The Results section discusses correlations in an analysis of religion and abortion responses, but it gives no rule classifying correlations as ‘moderate.’ Searches for moderate-correlation thresholds and for the seven cognitive domains found no relevant passage in this paper. The cited paper’s References section lists a separate 1988 Cohen book, but the paper itself does not state the classification attributed to it. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

Despite the common occurrence of chronic cognitive subjective symptomology after mTBI, extant research shows a lack of a consistent relationship with cognitive performance on formal neuropsychological examination, including in military samples.

“Despite the common occurrence of chronic cognitive subjective symptomology after mTBI, extant research shows a lack of a consistent relationship with cognitive performance on formal neuropsychological examination, including samples of military personnel”

• cites Mac Donald et al., 2017 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

These findings align with prior studies and provide some of the strongest evidence to date that in unselected mTBI cases, lower cognitive performance does not chronically persist relative to controls.

“These findings align with prior studies and provide some of the strongest evidence to date that in unselected mTBI cases, lower cognitive performance does not chronically persist relative to controls (Belanger et al., 2005; Binder et al., 1997; Frencham et al., 2005; Karr et al., 2014; Rohling et al., 2011; Schretlen & Shapiro, 2003).”

• cites Belanger et al., 2005 sourceCould not verify

  The supplied copy contains an abstract stating that unselected or prospective samples showed no residual neuropsychological impairment by three months, but no corresponding passage from the paper’s body was available. Searches for unselected samples and persistent deficits returned only the abstract and references; under the specified evidence rule, the abstract cannot establish the verdict. (LLM, conf=0.72)

  Experimental — accuracy not yet measured
• cites Binder et al., 1997 sourceNot checked — no full text of the source
• cites Frencham et al., 2005 sourceNot checked — no full text of the source

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S3 (load-bearing).

PPCS are especially common among U.S. Veterans and Service Members who sustained mTBI in the post-9/11 wars, including Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn.

“PPCS are especially common among U.S. Veterans and SMs who sustained mTBI in the post-911 wars, including Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND)”

• cites Cifu et al., 2013 sourceNot checked — no full text of the source
• cites Hendricks et al., 2013 sourceNot checked — no full text of the source
• cites Taylor et al., 2012 sourceCould not verify

  The Introduction discusses how often mild TBI occurred among Afghanistan and Iraq veterans, while the Results and Conclusions report psychiatric diagnoses and pain among VA users diagnosed with TBI. Neither establishes how common persistent postconcussive symptoms (PPCS) are after mTBI. A PPCS study appears in the Reference List, but this paper does not report its PPCS finding; the passages also do not address Operation New Dawn. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Blast-related mTBI may have more enduring long-term effects on cognition compared to blunt mTBI, but the evidence is mixed.

“Another factor specific to military populations with mixed research evidence is the concern that blast-related mTBI has more enduring long-term effects on cognition compared to blunt mTBI”

• cites Belanger et al., 2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Martindale et al., 2020 sourcePartly supported

  The Discussion (page not available in our copy) says findings on blast-related versus non-blast mTBI are mixed: some studies find no cognitive difference, while others find subtle differences associated with blast exposure. The paper also raises the possibility of persisting cognitive difficulties, but it does not establish that effects of blast-related mTBI last longer than those of blunt mTBI. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The use of measures recommended as NIH NINDS TBI common data elements allows other studies to compare their results to ours.

“Finally, the use of measures recommended as NIH NINDS TBI common data elements allows other studies to compare their results to ours (Hicks et al., 2013; Report Viewer | NINDS Common Data Elements, n.d.)”

• cites Hicks et al., 2013 sourceSupported
• cites Report Viewer | NINDS Common Data Elements, n.d.Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The physical and mental health symptom measure covariates showed less significance in the models than anticipated, but results were consistent with smaller studies that also measured performance validity.

“The physical and mental health symptom measure covariates showed less significance in the models than anticipated, but results were consistent with smaller studies that also measured performance validity (Wisdom et al., 2014).”

• cites Wisdom et al., 2014Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

May combine two claims.

Using the original one-item measure, the only significant reduction was for verbal fluency in those with a medium level (10-89) of controlled blast exposures compared to none, but it was not significant for the high level (90+) group.

“Using our original one-item measure, the only significant reduction was for verbal fluency in those with a medium level (10–89) of controlled blast exposures compared to none, but it was not significant for the high level (90+) group.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

May combine two claims.

For the comparison of 1-2 mTBIs to no TBIs in multivariable models, coefficients ranged from −0.09 (Attention) to 0.05 (Verbal Fluency) and all adjusted p-values were 1 except for Executive Function (p=0.42).

“Coefficients for the comparison of 1–2 mTBIs to no TBIs ranged from −0.09 (Attention) to 0.05 (Verbal Fluency) and all adjusted p-values were 1 except for Executive Function (p=0.42).”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The repetitive mTBI group was receiving more medication classes that might compromise cognition than TBI negative controls (p=0.003), but the mean difference (0.2) and effect size (Cohen's d=0.18) were very small.

“The repetitive mTBI group was receiving more medication classes that might compromise cognition (p=0.003), but the mean difference (0.2) and effect size (Cohen’s d=0.18) versus the TBI negative controls were very small.”

May combine two claims.

In sensitivity analyses replacing the three mTBI groups with number of mTBIs as a continuous variable, number of blast-related mTBIs, and time since first and last mTBI, none showed significant relationships of mTBIs with any of the seven cognitive domain outcomes after adjustment for multiple comparisons, except total number of blast-related mTBIs on Verbal Fluency (raw p=0.028; adjusted p=0.2) и

“Similar to the primary analysis, none of these sensitivity analyses showed significant relationships of mTBIs with any of the seven cognitive domain outcomes after adjustment for multiple comparisons, with all of the adjusted p-value for mTBIs above 0.05 even before adjustment except for total number of blast-related mTBIs on Verbal Fluency (raw p=0.028; adjusted p=0.2) and repetitive versus non”

• Also stated in: § DISCUSSION · plain

  “Additional sensitivity analyses also showed non-significance for all other TBI explanators examined, namely number of mTBIs as a continuous variable, number of blast-related mTBIs, and years since first and last mTBI.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The sample's mean age at enrollment was 39.7 years and mean time since index event was 9.7 years.

“Overall, the sample’s mean age at enrollment was 39.7 years and their mean time since index event was 9.7 years.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

There were no differences across TBI groups for being on an antidepressant (p=0.24) or a cognitive-enhancing medication (p=0.28).

“Regarding medications, there were no differences across TBI groups for being on an antidepressant (p=0.24) or a cognitive-enhancing medication (p=0.28).”

May combine two claims. The quote only partly states this claim.

For repetitive mTBI (3+ mTBIs) versus controls in univariate models, coefficients ranged from −0.17 (Fine Motor and Dexterity) to 0.18 (Verbal Fluency), and adjusted p-values ranged from p=0.06 (Verbal Fluency) to 1 (three domains).

“Coefficients for the comparison of 3+ mTBIs to no TBIs ranged from −0.17 (Fine Motor and Dexterity) to 0.18 (Verbal Fluency).”

• Also stated in: § Cognitive performance across mTBI groups and their unadjusted comparisons · plain

  “For repetitive mTBI (3+ mTBIs) versus controls, p-values ranged from p=0.06 (Verbal Fluency) to 1 (three domains).”

May combine two claims.

Higher estimated pre-exposure intellectual function (NIHTB-CB Picture Vocabulary test) was related to higher scores on other cognitive measures, and education level had a significant effect on four domains.

“As also expected, higher estimated pre-exposure intellectual function (NIHTB-CB Picture Vocabulary test) was related to higher scores on other cognitive measures, and education level had a significant effect on four domains.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

May combine two claims.

For the comparison of 3+ mTBIs to no TBIs in multivariable models, coefficients ranged from −0.04 (Processing Speed and Executive Function) to 0.17 (Verbal Fluency) and the only adjusted p-value under 1 was Verbal Fluency (adjusted p=0.15).

“Coefficients for the comparison of 3+ mTBIs to no TBIs ranged from −0.04 (Processing Speed and Executive Function) to 0.17 (Verbal Fluency) and the only adjusted p-value under 1 was Verbal Fluency (adjusted p=0.15).”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

May combine two claims.

Findings were consistently negative across sensitivity analyses, including when mTBIs were modeled as a continuous variable, when blast-related mTBIs were analyzed, and when years since first and last mTBI were considered.

“Findings were also consistently negative across sensitivity analyses (e.g., mTBIs as a continuous variable, number of blast-related mTBIs, or years since first and last mTBI).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The sample was predominantly male (87%), educated with at least some college or technical school (86%), had an enlisted rank (84%), and served in the Army (65%).

“Overall, the sample was diverse racially (27% non-White) and ethnically (17% Hispanic), was predominantly male (87%), educated with at least some college or technical school (86%), had an enlisted rank (84%), and served in the Army (65%).”

May combine two claims. The quote only partly states this claim.

For the non-repetitive TBI group (1-2 mTBIs) versus controls in univariate models, coefficients ranged from −0.09 (Episodic Memory and Processing Speed) to 0.02 (Verbal Fluency), and adjusted p-values ranged from p=0.09 (Executive Function) to 1 (two domains).

“Coefficients for the comparison of 1–2 mTBIs to no TBIs ranged from −0.09 (Episodic Memory and Processing Speed) to 0.02 (Verbal Fluency).”

• Also stated in: § Cognitive performance across mTBI groups and their unadjusted comparisons · plain

  “For the non-repetitive TBI group (1–2 mTBIs) versus controls, adjusted p-values ranged from p=0.09 (Executive Function) to 1 (two domains).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The relationships between the seven domains in the sample showed moderate correlations, suggesting that further collapsing of domains may be possible.

“The relationships between the seven domains in our sample showed ‘moderate’ correlations, suggesting that further collapsing of domains may be possible.”

Classified as probably not a substantial claim. May combine two claims.

For the current analyses, only baseline data were used, and participants who failed any of the three performance validity tests were excluded.

“For the current analyses, only data collected at baseline assessment were utilized, and participants who failed any of the three tests of performance validity described further below were excluded.”

May combine two claims.

For all additional sensitivity models, all GVIF values were below 2.4, indicating no evidence of multicollinearity.

“For all of these additional models, all GVIF values were below 2.4, indicating no evidence of multicollinearity (Table S5).”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

May combine two claims.

The literature remains inconclusive on whether repeated mTBI affects objective cognitive performance, as many studies have failed to demonstrate an effect.

“However, the literature remains inconclusive, as many other studies have failed to demonstrate an effect of repeated mTBI on objective cognitive performance”

• cites Belanger et al., 2010Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Cooper et al., 2018 sourceNot checked — no full text of the source
• cites Macciocchi et al., 2001Not checked — no full text of the source

May combine two claims.

The study has the largest sample size to date with comprehensive neurocognitive testing in Veterans and SMs with blast-related mTBI.

“Our study has the largest sample size to date with comprehensive neurocognitive testing in Veterans and SMs with blast-related mTBI.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The strong association with lower scores as age increased was expected given the use of raw scores rather than population-normed scores to calculate sample-based Z-scores.

“The strong association with lower scores as age increased was expected given our use of raw scores rather than population-normed scores to calculate the sample-based Z-scores.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S3 (load-bearing).

20% or more of patients with mTBI experience persistent post-concussion symptoms (PPCS).

“Nevertheless, 20% or more of patients with mTBI experience persistent post-concussion symptoms (PPCS)”

• cites Lagacé-Legendre et al., 2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Key strengths of the study include the very large and ethnically and racially diverse sample, the inclusion of mTBI-negative but deployed controls, and the exclusion of cases with profiles of invalid testing.

“Key strengths of this study include the very large and ethnically and racially diverse sample, the inclusion of mTBI-negative but deployed controls, and the exclusion of cases with profiles of invalid testing.”

• AssumptionRests on an assumption: The use of dissimilar controls and/or inclusion of cases with diminished or feigned effort are important sources of potential bias toward positive associations between mTBI and cognitive decline.

May combine two claims.

The mTBI negative controls were recruited through the same processes as the mTBI positive participants, providing a relevant control group with similar background characteristics and experiences.

“Notably, our mTBI negative controls were recruited through the same processes as the mTBI positive participants which provided a relevant control group with similar background characteristics and experiences.”

• AssumptionRests on an assumption: The use of dissimilar controls and/or inclusion of cases with diminished or feigned effort are important sources of potential bias toward positive associations between mTBI and cognitive decline.

Classified as probably not a substantial claim.

There is inconclusive research regarding the risk of chronic neurocognitive decrements after a single mTBI or even repeated mTBIs.

“Taken together, there is inconclusive research regarding the risk of chronic, neurocognitive decrements after a single mTBI or even repeated mTBIs.”

Probably not a substantial claim: may not pass S2 (checkable).

The negative findings do not rule out the potential for a vulnerable subset of individuals who do experience chronic objective cognitive changes after mTBI.

“While providing an encouraging message to Veterans, SMs, and providers, these negative findings do not rule out the potential for a vulnerable subset of individuals who do experience chronic objective cognitive changes after mTBI.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The parent study, including the database registry and all secondary analyses, was approved by the local Institutional Review Boards at each PLS enrollment site, and all participants provided written consent prior to any study procedures.

“The parent study, including the database registry and all secondary analyses, was approved by the local Institutional Review Boards at each of the PLS enrollment sites. All participants provide written consent prior to any study procedures.”

Probably not a substantial claim: may not pass S3 (load-bearing).

PPCS typically include cognitive symptoms such as decreased concentration, memory, and processing speed, in addition to somatic and emotional symptoms.

“PPCS typically include cognitive symptoms, such as decreased concentration, memory, and processing speed, in addition to somatic and emotional symptoms, such as headache, dizziness, disordered sleep, fatigue, irritability, increased arousal, and sensitivity to light and sound”

• cites Brenner et al., 2009 sourceNot checked — no full text of the source
• cites Stein & McAllister, 2009 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

People associate concussion with negative outcomes and therefore experience a type of 'diagnosis threat'.

“This is thought to occur because people associate concussion with negative outcomes and therefore experience a type of “diagnosis threat” (Suhr & Gunstad, 2002).”

• cites Suhr & Gunstad, 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Another strength was the a-priori designation of seven cognitive domain composite scores for the dependent variable and appropriately adjusting for Type 1 error.

“Another strength was the a-priori designation of seven cognitive domain composite scores for the dependent variable and appropriately adjusting for Type 1 error.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The sex-related findings are consistent with the literature in the general population, especially for episodic memory and processing speed.

“These sex-related findings are consistent with the literature in the general population, especially for episodic memory (Asperholm et al., 2019) and processing speed (Camarata & Woodcock, 2006).”

• cites Asperholm et al., 2019 sourceNot checked — no full text of the source
• cites Camarata & Woodcock, 2006 sourceNot checked — no full text of the source

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Attributional styles are mutable and can be successfully addressed.

“From a clinical perspective, it is important to note that attributional styles are mutable and can be successfully addressed (Peters et al., 2011) .”

• cites Peters et al., 2011 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

There was no presence of multicollinearity in any multivariable model (all GVIF < 2.4).

“There was no presence of multicollinearity in any model (all GVIF < 2.4, full results available on-line in supplementary Table S2).”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

May combine two claims.

The study sample consists entirely of current and former military SMs who often sustained mTBI during combat deployment and/or blast-related mTBI, so the findings may not generalize well to civilians.

“Given the LIMBIC-CENC research mission, our study sample consists entirely of current and former military SMs who often sustained mTBI during combat deployment and/or blast-related mTBI, so the findings may not generalize well to civilians.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S2 (checkable).

Self-reported concerns about cognitive difficulties in persons in the chronic phase following mTBI are likely best treated with a holistic approach that considers common comorbid conditions and situational factors.

“This suggests that self-reported concerns about cognitive difficulties in persons in the chronic phase following mTBI are likely best treated with a holistic approach that considers common comorbid conditions and situational factors that could be associated with longstanding cognitive complaints.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

May combine two claims.

The study sample was predominantly male, so the findings may not generalize well to women.

“Our study sample, which mirrored the broader U.S. military population in gender make up, was predominantly male, so our findings may also not generalize well to women.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S3 (load-bearing).

The retrospective identification of historical mTBI is prone to recall bias.

“Additionally, although we used a validated structured interview method with layers of quality assurance, the retrospective identification of historical mTBI is prone to recall bias.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The lack of difference in cognitive performance may be, in part, related to benefit gained from treatment since participants had access to specialized brain injury rehabilitation services.

“The lack of difference in cognitive performance may be, in part, related to benefit gained from treatment since our participants had access to specialized brain injury rehabilitation services in the Military and/or Veterans healthcare system.”

• AssumptionRests on an assumption: The set of covariates included in the multivariable models adequately controls for confounding of the relationship between mTBI history and cognitive performance.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

Strategies for addressing misattribution may also be beneficial.

“Strategies for addressing misattribution may also be beneficial and further research on behavioral interventions for patients with tightly held negative beliefs on the impact of their remote concussions is also recommended.”

May combine two claims.

The cross-sectional design precludes understanding of later cognitive changes which may be due to TBI or other comorbidities as well as subtle changes that may be related to other aspects of deployment.

“Foremost is the cross-sectional design, which precludes understanding of later cognitive changes which may be due to TBI or other comorbidities as well as subtle changes that may be related to other aspects of deployment.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Regression models are increasingly prone to overfitting as the number of covariates increases.

“While our consideration of multiple potential confounders is a strength, regression models are increasingly prone to overfitting as the number of covariates increases (Babyak, 2004).”

• cites Babyak, 2004 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

It is possible the study may not have selected the most sensitive measures to capture cognitive effects.

“Although our use of pre-selected cognitive domain composite scores sharpened our scientific rigor, it is possible we may have not selected the most sensitive measures to capture cognitive effects.”