Associations among aerobic physical activity, mild traumatic brain injury history, and health‐related quality of life in military service members and Veterans: A LIMBIC‐CENC study

Abstract

Background

Mild traumatic brain injury (mTBI) is common among military service members. Moderate‐to‐vigorous aerobic exercise (MVAE) is a modifiable behavior with potential benefits for individuals following mTBI but is poorly understood for long‐term mTBI health.

Objective

To explore the associations between mTBI history and MVAE participation and appreciate their association with health‐related quality of life (HR‐QOL) among service members and Veterans.

Methods

Data from a larger study were used in these secondary cross‐sectional analyses. Lifetime mTBI history (0, 1–2, 3+) was captured via validated structured interviews. Self‐reported weekly MVAE (none, below, meeting, or ≥2 times the recommendation) was recorded from the Behavioral Risk Factor Surveillance System questionnaire. Participants’ HR‐QOL was self‐reported via Traumatic Brain Injury‐Quality of Life instrument and the Patient Health Questionnaire‐9 (depression symptoms). Univariate mTBI history and MVAE associations were assessed via Pearson's chi‐square and Kendall's Tau. Multivariable linear regression models with unstandardized beta values and 95% confidence intervals were fit for each HR‐QOL questionnaire outcome, with current age, sex, and posttraumatic stress disorder symptoms as covariates (α = .05).

Results

Among the 1995 participants (87.7% male; aged 41.7 ± 10.1 years), those meeting or exceeding (≥2 times) MVAE recommendations had significantly higher HR‐QOL for fatigue, executive function, pain interference, resilience, social participation, and depression than the inactive MVAE group. Exceeding MVAE recommendations by ≥2 times was also significantly associated with better self‐reported cognition – general concerns. Those who participated in exercise but didn't meet the MVAE recommendations had higher pain interference, social participation, and depression scores compared to the inactive group. More lifetime mTBIs were associated with worse HR‐QOL across all domains. Level of MVAE participation was not dependent on mTBI history.

Conclusions

More MVAE was associated with better TBI‐related HR‐QOL regardless of mTBI history. MVAE is recommended for service members and Veterans due to these findings and previously reported health benefits.

INTRODUCTION

Approximately 500,000 U.S. military service members have sustained mild traumatic brain injuries (mTBIs) since the year 2000. ¹ The true prevalence is likely far greater, given that only 50% are expected to seek health care for their injuries. ² Among military service members and veterans (SMVs), mTBI can lead to negative short‐ and long‐term effects on cognitive, emotional, and physical wellbeing, including decreased health‐related quality of life (HR‐QOL). ³ , ⁴ , ⁵ For example, mTBI history among SMVs is associated with worse physical, mental, cognitive, and social aspects of HR‐QOL. ³ , ⁴ , ⁵ Measuring long‐term HR‐QOL outcomes among SMVs after mTBI can be complicated by the impact of common co‐occurring factors like mood‐related disorders (eg, depression, posttraumatic stress disorder [PTSD]), chronic pain, and health‐related behaviors (eg, physical activity). Additionally, the effects of mTBI history on long‐term HR‐QOL may be reduced when accounting for factors such as health‐related behaviors like aerobic exercise. ⁵

Aerobic exercise is a promising intervention for improving brain health among SMVs with mTBI, and it is a standard care recommendation to facilitate recovery following mTBI in athletes. ⁶ , ⁷ A recent meta‐analysis reported overall benefits to HR‐QOL from exercise interventions for people with TBI. ⁸ In light of these demonstrated benefits and evidence for improving multiple other aspects of brain health after TBI, ⁹ there is promise in learning about the effects of aerobic exercise on measures of long‐term brain health among individuals with a history of mTBI. In particular, many SMVs experience one or more mTBIs, ¹⁰ which may result in subsequent chronic symptoms or other long‐term sequelae. Examining how modifiable health‐related behaviors, such as physical activity, may interact with long‐term HR‐QOL outcomes will help guide efforts to reduce lasting effects of mTBI on SMVs.

In this exploratory cross‐sectional study, we examined the associations among weekly moderate‐to‐vigorous aerobic exercise (MVAE) participation, mTBI history, and multiple patient‐reported measures of HR‐QOL in a large sample of SMVs. The aims of this study were to examine (1) associations of MVAE participation with HR‐QOL; (2) associations of mTBI history with HR‐QOL; (3) associations of MVAE participation with HR‐QOL outcomes across mTBI history; and (4) associations between mTBI history and MVAE participation. We hypothesized that (1) higher MVAE participation would be associated with better HR‐QOL; (2) more lifetime mTBIs would be associated with worse HR‐QOL; (3) the relative association of MVAE participation with HR‐QOL outcomes would be stronger among those with more lifetime mTBIs; and (4) MVAE participation would be lower among those with more lifetime mTBIs.

MATERIALS AND METHODS

This study was a secondary analysis of data collected from formerly deployed SMVs with combat exposure during the initial participant visit of a prospective longitudinal study (PLS), the centerpiece study of the successively funded Long‐Term Impact of Military‐Relevant Brain Injury Consortium and Chronic Effects of Neurotrauma Consortium (LIMBIC‐CENC). The purpose, recruitment processes, eligibility criteria, and overall methodology of the LIMBIC‐CENC PLS study have been previously documented. ¹¹ , ¹² , ¹³ The LIMBIC‐CENC PLS captures many different health‐related variables among SMVs with an overarching goal of improving clinical care and well‐being for those who experience mTBI. Data for the present study were gathered during each participant's initial (baseline) study visit, which has been previously described. ¹¹ , ¹⁴ The LIMBIC‐CENC PLS study was approved by the institutional review boards at all 10 participating sites, and each participant provided their written informed consent prior to engaging in any research activities. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines were used to guide reporting. ¹⁵

Participants

Inclusion criteria for participation in LIMBIC‐CENC PLS were (1) age 18 years or older, (2) military deployment to a combat zone, and (3) combat exposure as defined by the Deployment Risk and Resiliency Inventory Section D score >1 on any item. ¹⁶ Exclusion criteria were (1) any history of moderate, severe, or penetrating TBI; or (2) history of major neurologic or psychiatric disorder causing a significant reduction in independent living status (eg, schizophrenia). Participants without a history of TBI were included as controls, as were those with common mental health or medical conditions (eg, PTSD, depression, hypertension, chronic pain). Participants were included in the present analyses if data were available for all primary predictors, outcomes, and selected covariates. In cases where there were missing data, individual participants were removed from all analyses.

Measurement of moderate‐to‐vigorous aerobic exercise participation

Participants self‐reported their engagement in regular physical activity during the month leading up to the baseline study visit using the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System physical activity questionnaire. ¹⁷ Participants reported the activity they engaged in the most (primary activity) along with the frequency and duration of participation in that activity. ¹⁸ Participants were also asked about engagement in any physical activities other than their primary activity; however, responses to this item were missing for a large portion of our analysis sample (n = 840/1643; 51.1%), and therefore MVAE participation measurements were based solely on primary physical activity. Metabolic equivalent values for each activity were provided in the user guidelines for the physical activity questionnaire to categorize them as nonaerobic, light aerobic, moderate aerobic, or vigorous aerobic intensities. ¹⁹ For each participant's primary activity, we calculated the total amount of time spent per week at that aerobic intensity, and we subsequently categorized participants into MVAE participation groups according to guidelines provided by the U.S. Department of Health and Human Services (DHHS) of (1) those that did not participate in any aerobic physical activity (Inactive); (2) those that did participate in aerobic physical activity, but did not meet DHHS recommendations (Insufficiently Active); (3) those that met the minimal DHHS recommendation of 150 minutes per week of moderate intensity aerobic activity, 75 minutes of vigorous aerobic activity, or equivalent combination thereof (Active); and (4) those that exceeded the minimal DHHS aerobic physical activity participation guidelines by at least twice the recommended weekly volume (Highly Active). ²⁰

Measurement of mTBI history

The definition of mTBI was based on the Veterans Affairs/Department of Defense common definition of mTBI, in alignment with the American Congress of Rehabilitation Medicine. ²¹ , ²² Consistent with related work including an overlapping participant sample, ²³ mTBI history for the present study was operationalized into three separate groups for analyses: those reporting no lifetime mTBIs (0 mTBI); those reporting one or two lifetime mTBIs (1–2 mTBI); and those reporting three or more lifetime mTBIs (3+ mTBIs). A structured interview with validated instruments was followed by a rigorous data integrity review process to capture and characterize mTBI history across deployment and nondeployment time periods of life. ²⁴ With use of the Virginia Commonwealth University retrospective concussion diagnostic interview, ²⁴ each participant reported potential mTBI events that were then assessed and categorized through a diagnostic interview and subsequent algorithm‐based classification as no mTBI or mTBI and further subdivided by the presence of posttraumatic amnesia. Each individual's classification was reviewed by the PLS study site principal investigator; compared to all interview elements, including unstructured free‐text data and available medical records; and further vetted by a central study monitor or an expert committee if necessary. ²⁴

Measurement of health‐related quality of life

Self‐reported HR‐QOL was ascertained from the Traumatic Brain Injury Quality of Life (TBI‐QOL) and Patient Health Questionnaire‐9 (PHQ‐9) instruments. ²⁵ , ²⁶ , ²⁷ Nine different domains of HR‐QOL were evaluated in the present study. Eight domains were from the TBI‐QOL battery: ²⁵ anxiety; cognition—general concerns; emotional and behavioral dyscontrol; fatigue; executive function; pain interference (the degree to which pain negatively affects activities of daily living); resilience; and ability to participate in social roles and activities. For each of these domains, participants responded to individual items via 5‐point Likert scales unique to each inventory. Total scores were calculated and subsequently transformed into T‐scores according to interpretation guidelines (mean = 50, SD = 10). ²⁵ , ²⁶ Higher T‐scores were associated with better outcomes (eg, more adaptive functioning) for the cognition, executive functioning, resilience, and social participation domains. Conversely, higher T‐score were associated with worse outcomes (eg, less adaptive functioning) for the anxiety, emotional and behavioral dyscontrol, fatigue, and pain interference domains.

The PHQ‐9 instrument measures depression symptoms and severity. ²⁷ Participants responded to nine individual items via a 4‐point Likert scale, and the raw total score was derived as the sum of individual responses. For consistency with the TBI‐QOL measures, PHQ‐9 raw total scores were converted to the T‐scores equivalent of the Patient‐Reported Outcomes Measurement Information System (PROMIS) 20‐item depression inventory. Specifically, we used a crosswalk table developed through validated linking procedures (eg, linked item response theory techniques) as part of the PRO Rosetta Stone (PROsetta Stone) project. ²⁸ Higher depression T‐scores indicated higher depression symptom severity (worse outcome).

Statistical analyses

To address our first two aims, the associations of MVAE participation and mTBI history with HR‐QOL outcomes were evaluated using separate multivariable linear regression models for each outcome measure. All models included MVAE participation group and mTBI history group as ordinal primary predictors of interest. Participant self‐reported sex, age, and posttraumatic stress symptoms (posttraumatic stress disorder checklist for the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition [PCL‐5]) ²⁹ scores were included in each model as covariates (supplemental methods). The referent group for comparison of MVAE participation effects was the Inactive group, and the referent group for comparison of mTBI effects was the 0 mTBI group. Unstandardized beta values (β) and associated 95% confidence intervals (95% CI) were calculated and considered statistically significant if the 95% CI did not include zero.

Planned sensitivity analyses were conducted to explore whether including depression and anxiety domain T‐scores affected the associations of MVAE participation and mTBI history with each of the other domain outcomes. We compared the main effects (β [95% CI]) for models before and after adjusting for anxiety/depression T‐scores and calculated the change in β‐values between models.

To address our third aim, we tested for interaction effects between MVAE participation and mTBI history on each outcome T‐score. Overall interaction effects were tested and considered statistically significant if the interaction term p value was <.05. Planned stepdown analyses were pairwise comparisons between MVAE groups (Inactive, Insufficiently Active, Active, and Highly Active) within each level of mTBI history (0 mTBI, 1–2 mTBIs, 3+ mTBIs) only in cases of a statistically significant interaction effect.

To address our fourth aim, we performed a Χ ² test of proportions with accompanying Kendall's Tau‐b (T _b) to examine whether the association between MVAE and mTBI history groups indicated a directional relationship.

All statistical analyses for this study were performed using SPSS version 28 (Armonk, NY) with α = .05 a priori. We recognize the potential for false positive results when conducting multiple hypothesis tests. As an exploratory study with secondary data analyses, statistical results were intended to identify potentially meaningful statistical associations, and we did not correct for multiple comparisons.

RESULTS

The included SMV sample (n = 1995) was predominantly male (n = 1750; 87.7%), identified as non‐Hispanic and white (n = 1446; 72.5%), and were 41.7 ± 10.1 years old on average (Table 1). Most participants sustained at least one mTBI (n = 1635; 82.0%) and did not meet the minimum MVAE recommendations (Inactive or Insufficiently Active; n = 1313; 65.8%; Table 1).

TABLE 1.

Participant characteristics.

Characteristic	Sample descriptive n = 1995
Age (years), mean (SD)	41.7 (10.1)
Sex, n (%)
Female	245 (12.3)
Male	1750 (87.7)
Race and ethnicity, n (%)
American Indian or Alaska Native	23 (1.2)
Asian	39 (2.0)
Black or African American	356 (17.8)
Pacific Islander	16 (0.8)
White or Caucasian	1446 (72.5)
No racial identity reported a	115 (5.8)
Hispanic or Latino/a ethnicity b	342 (17.1)
Lifetime mild TBI history group, n (%)
0	360 (18.0)
1–2	951 (47.7)
3+	684 (34.3)
Moderate‐to‐vigorous aerobic activity group, n (%)
Inactive	689 (34.5)
Insufficiently active	624 (31.3)
Active	348 (17.4)
Highly Active	334 (16.7)
Functional domain outcome scores, mean (SD) c , d
Anxiety	54.2 (10.7)
Cognition – general concerns	37.7 (7.8)
Emotional and behavioral dyscontrol	53.1 (8.1)
Fatigue	55.6 (8.7)
Executive function	38.4 (7.0)
Pain interference	56.2 (9.1)
Resilience	45.4 (9.4)
Ability to participate in social roles and activities	44.3 (6.5)
Depression symptoms (cross‐walked PROMIS depression T‐Score)	55.5 (9.8)

^a In response to a question about racial and ethnic identity, participants indicated “other” (n = 91), “don't know/not sure” (n = 11), or otherwise intentionally opted not to respond (n = 13).

^b In response to ethnicity, n = 20 participants indicated “don't know/not sure” and another n = 8 intentionally opted not to respond.

^c Functional domain outcome scores were T‐scores derived from a TBI‐QoL battery with the exception of depression, which is presented as raw PHQ‐9 total score as well as the converted T‐score analogous to the PROMIS Depression Symptoms module T‐score.

^d Functional domain scores are presented as mean (SD) unless otherwise indicated.

Abbreviations: PHQ‐9, Patient Health Questionnaire 9; PROMIS, Patient‐Reported Outcomes Measurement Information System; TBI, traumatic brain injury; TBI‐QoL, Traumatic Brain Injury Quality of Life.

Participation in MVAE and HR‐QOL Outcomes

Participants in the Highly Active MVAE participation groups reported better HR‐QOL than the Inactive group for cognition – general concerns (β = 1.11), fatigue (−1.95), executive function (1.51), pain interference (−1.55), resilience (2.84), social participation (2.03), and depression symptoms (−1.88) (see Table 2 and Figure 1). Similarly, participants in the Active group reported better HR‐QOL than the Inactive group for fatigue (β = ‐1.87), executive function (0.99), pain interference (−1.77), resilience (2.39), social participation (2.17), and depression symptoms (−2.04). Better pain interference (−1.00), social participation (0.77), and depression symptoms (−1.14) scores were also observed in the Insufficiently Active group compared to the Inactive group. There was no main effect observed for the MVAE group on anxiety or emotional and behavioral dyscontrol scores.

TABLE 2.

Results of multivariable linear regression models in the full sample.

Score interpretation	Anxiety	Cognition – general concerns	Emotional and behavioral dyscontrol	Fatigue	Executive function	Pain interference	Resilience	Social participation	Depression symptoms
	Higher score = worse/less adaptive	Higher score = better/more adaptive	Higher score = worse/less adaptive	Higher score = worse/less adaptive	Higher score = better/more adaptive	Higher score = worse/less adaptive	Higher score = better/more adaptive	Higher score = better/more adaptive	Higher score = worse/less adaptive
	β (95% CI)	β (95% CI)	β (95% CI)	β (95% CI)	β (95% CI)	β (95% CI)	β (95% CI)	β (95% CI)	β (95% CI)
MVAE group	p = .306	p = .010	p = .195	p < .001	p < .001	p = .001	p < .001	p < .001	p < .001
Insufficiently active	0.55 (−0.35 to 1.45)	−0.14 (−0.86 to 0.57)	0.02 (−0.74 to 0.77)	−0.56 (−1.36 to 0.23)	−0.27 (−0.68 to 0.63)	−1.00* (−1.83 to −0.18)	0.25 (−0.67 to 1.17)	0.77* (0.15 to 1.39)	−1.14* (−1.94 to −0.33)
Active	−0.34 (−1.42 to 0.74)	0.85 (−0.01 to 1.71)	−0.90 (−1.81 to 0.001)	−1.87* (−2.82 to −0.92)	0.99* (0.20 to 1.77)	−1.77* (−2.76 to −0.78)	2.39* (1.29 to 3.49)	2.17* (1.43 to 2.91)	−2.04* (−3.01 to −1.08)
Highly active	−0.29 (−1.38 to 0.841)	1.11* (0.24 to 1.97)	−0.28 (−1.20 to 0.63)	−1.95* (−2.91 to −0.98)	1.51* (0.72 to 2.31)	−1.55* (−2.55 to −0.55)	2.84* (1.72 to 3.95)	2.03* (1.28 to 2.78)	−1.88* (−2.86 to −0.91)
Lifetime mTBI group	p < .001	p < .001	p < .001	p < .001	p < .001	p < .001	p = .047	p < .001	p < .001
1–2 mTBI	2.58* (1.57 to 3.59)	−2.24* (−3.04 to −1.43)	1.50* (0.65 to 2.35)	2.05* (1.16 to 2.95)	−2.35* (−3.09 to −1.61)	2.98* (2.05 to 3.91)	−0.98 (−2.01 to 0.06)	−1.82* (−2.52 to −1.13)	2.41* (1.50 to 3.31)
3+ mTBI	3.95* (2.88 to 5.03)	−4.27* (−5.13 to −3.42)	3.51* (2.61 to 4.41)	3.49* (2.54 to 4.44)	−4.05* (−4.83 to −3.26)	4.89* (3.90 to 5.88)	−1.39* (−2.49 to −0.29)	−2.40* (−3.14 to −1.66)	3.67* (2.71 to 4.64)

Note: Unstandardized beta values and 95% confidence intervals were calculated. Confidence intervals that didn't include zero were considered statistically significant. Main effect p values reflect overall statistical significance for the given predictor in each model. All models included participant sex, age, and PCL5 screening threshold (>33 total score) as covariates. Abbreviations: CI, confidence interval; mTBI, mild traumatic brain injury (referent category = 0 mTBI); MVAE, moderate‐to‐vigorous aerobic exercise (referent category = Inactive).

^*Statistically significant effect in comparison to the referent category.

FIGURE 1.

Functional domain T‐score distributions by mild traumatic brain injury history (mTBI group) and participation in moderate‐to‐vigorous aerobic exercise (MVAE group). Tukey box plots represent the distribution of scores within each mTBI group. Gray boxes represent the range of T‐score values from −1 SD to +1 SD around the general population normative mean (T‐score = 50 ± 10). Abbreviations: PROMIS, Patient‐Reported Outcomes Measurement Information System; QoL, quality of life.

mTBI history and HR‐QOL Outcomes

Compared to SMVs with no mTBIs, those with a history of 1–2 mTBIs had worse HR‐QOL outcome scores for all outcome measures except resilience (β = −0.98), and SMVs with 3+ mTBIs had worse HR‐QOL outcome scores for every outcome measure (Table 2; Figure 1). The relative effect sizes (ie, β‐values) for those in the 3+ mTBI group were higher for all measures than the effect size for those in the 1–2 mTBI group.

Interaction effects of MVAE and mTBI

There were no statistically significant interaction effects for MVAE participation and mTBI history (all p values ≥.06).

Planned sensitivity analyses

Inclusion of depression and/or anxiety T‐scores as covariates in these models generally attenuated the relative effects (ie, β‐values) of MVAE participation and mTBI history across all outcome measures. The Supplemental Table includes the original β‐values, β‐values from models adjusted for depression and/or anxiety, and the change in β‐values between models.

Association between MVAE participation and mTBI history

The association between MVAE participation group and mTBI group was statistically significant (Χ ² ₆ = 14.506; p = .02; Figure 2); however, MVAE participation did not change consistently with increasing number of mTBIs (T _b = 0.30; p = .12).

FIGURE 2.

Participation in MVAE by lifetime mTBI history group. The interaction between MVAE and mild TBI history group was statistically significant: Χ ² ₆ = 14.506; p = .02; however, the relationship was not deemed to change uniformly in one direction (T _b = 0.30; p = .12). Abbreviations: mTBI, mild traumatic brain injury; MVAE, moderate‐to‐vigorous aerobic exercise.

DISCUSSION

Findings from this large study of combat‐exposed SMVs provide evidence supporting the benefits of engaging in MVAE for improving self‐reported HR‐QOL. Our observed positive association between actively participating in MVAE activities and better HR‐QOL outcomes was not dependent on a history of one or more mTBI. As such, despite the negative association between more mTBIs and worse HR‐QOL outcomes, MVAE appears to be a worthwhile health‐promoting behavior that warrants further study in this population.

Participation in MVAE and HR‐QOL

We observed that more frequent MVAE engagement, or at least meeting weekly MVAE recommendations, was generally associated with better HR‐QOL outcomes among combat‐exposed SMVs with varying mTBI histories. These results align with the broader literature surrounding exercise and QoL in diseased and healthy populations; a large meta‐analysis examining effects of physical activity on HR‐QOL reported that aerobic exercise improved outcomes across many of the domains in patients with neurologic conditions (Parkinson's, spinal cord injury, and multiple sclerosis) and generally healthy individuals, ³⁰ , ³¹ , ³² , ³³ , ³⁴ indicating physical activity benefits are present across subpopulations.

As a closer comparison to our study participants, exercise has been shown to improve HR‐QOL among military Veteran samples with PTSD, a common comorbidity with mTBI in this population. ³⁵ , ³⁶ Our findings also align with previous reports of lower depression symptoms being associated with aerobic exercise among individuals with mTBI history. ³⁷ , ³⁸ However, we did not observe an effect for MVAE participation and anxiety T‐scores (Table 2). Although the directionality and causality of statistical associations cannot be determined from our cross‐sectional study, it is possible that some SMVs who were experiencing higher anxiety symptoms might have been using aerobic exercise to address their symptoms, in alignment with the work noted previously. ³⁷ , ³⁸ In our sensitivity analyses, the inclusion of anxiety and depression T‐scores in models for all other HR‐QOL outcomes generally attenuated the relative effects of MVAE participation (Supplemental Table), which emphasizes the need to understand these complex relationships further.

Our definition of MVAE participation was based on the primary physical activity reported by each participant. We could not readily account for secondary aerobic activities due to limited available data, and we did not include resistance exercise activities (eg, strength training) in the present analyses. Findings from our study generally supported the hypothesis that higher MVAE participation was associated with better HR‐QOL among SMVs both with and without a history of mTBI(s) and regardless of the number of mTBIs. There is evidence that factors related to HR‐QOL are associated with exercise motivation and adherence; thus, latent factors may contribute to the exercise and HR‐QOL associations that we found. ³⁹ Future research should examine how symptoms such as anxiety are associated with exercise participation over time as well as how exercise may be used to treat mood‐related symptoms in SMVs. Taken together, exercise and factors related to HR‐QOL may have bidirectional associations, and our findings support the inclusion of aerobic exercise as a component of health promotion among SMVs.

mTBI history and HR‐QOL

The TBI‐QOL assessment battery was developed to assess the effects of TBI on multiple domains of HR‐QOL. ⁴⁰ Our findings align with that seminal work in that a higher number of mTBIs (1–2 and 3+ versus 0) was consistently associated with worse HR‐QOL across all eight of the TBI‐QOL measures we employed. We observed a potential dose–response related to mTBI history, where the relative effect sizes (β‐values) were larger among SMVs with three or more mTBIs than among SMVs with one or two mTBIs (Table 2). Additionally, our observation of worse depression symptoms in those with one or more mTBIs is similar to previous work among individuals with history of TBI. ⁴¹ , ⁴² Our sensitivity analyses reflected that the addition of anxiety and/or depression scores to each HR‐QOL outcome model attenuated the main effects of mTBI history when compared to the primary analysis models (Supplemental Table). Depression and anxiety symptoms, therefore, appear to be moderators of the associations between mTBI history and other measures of HR‐QOL and should be considered important clinical targets for the improvement of HR‐QOL among SMVs, despite their mTBI history.

MVAE participation and mTBI history

We hypothesized that more mTBIs would be associated with less frequent participation in MVAE among participants in this study. On the contrary, although MVAE participation was statistically associated with mTBI group in this study, we did not observe that there was a consistent decline in MVAE engagement with increasing mTBI history (Figure 2). Similarly, Jurick et al. recently examined mTBI history as a binary variable (one or more mTBI vs. no mTBI) among military personnel and reported that both groups had similar engagement in physical activity. ⁵ This previous study only reported mTBI sustained during combat deployment and not mTBI history from all environments as was operationalized in our study. However, these relationships have not been thoroughly investigated in this population, and more work is needed to better understand the role of physical activity in health promotion specifically among SMVs with histories of one or more mTBIs. The findings from Jurick et al. and our present study suggest that mTBI history may not be clearly correlated with engagement in aerobic exercise among SMVs. Exercise recommendations may not need to be specifically modified for SMVs with more mTBI exposure. Further, group‐level findings from our study may not reflect the breadth of individual variability in symptoms and pertinent comorbidities (eg, disordered sleep, chronic headache) across MVAE and mTBI groups. Future work should identify whether there are certain individuals who may benefit more from engagement in MVAE, as well as intervention paradigms that include MVAE alongside other treatments targeting specific symptoms (eg, depression symptoms).

Based on the potential benefits associated with MVAE in this population, we recommend that clinicians caring for SMVs inquire about physical activity participation, including frequency, intensity, type, and duration, both preinjury and postinjury. Clinicians and researchers should also work with SMVs to identify potential perceptual or actual barriers that may preclude exercise participation (eg, access to facilities and resources, physical limitations due to injury, fall risks, etc.) to tailor exercise recommendations to overcome those barriers.

Clinical implications

We did not measure the effect of an intervention with MVAE or mTBI on HR‐QOL in this study, and the direct clinical applicability of our findings are limited at this time. Normative data for each of the HR‐QOL outcome measures suggest that there is a mean T‐score value of 50 with an SD of 10 among individuals who have had a TBI (TBI‐QOL measures) or the general population (depression only). ²⁵ , ²⁶ , ²⁷ In our sample, the mean values for Cognition – General Concerns (37.7) and Executive Function (38.4) suggest worse average functioning among SMVs in this study compared with the general population with TBI as observed mean values were >1 SD below the normative mean. We report unstandardized β‐values in Table 2 which reflect the difference in T‐score for a given measure when comparing that particular group (eg, 3+ mTBI) to the referent group (0 mTBI). The largest observed β‐value was for pain interference among participants in the 3+ mTBI group (β = 4.89, 95% CI = 3.90, 5.88) relative to participants in the 0 mTBI group. Crudely interpreted, this finding suggests that SMVs with a history of three or more mTBIs have less than a half an SD of worse pain interference (negative outcome) compared to SMVs who have never sustained an mTBI, while accounting for MVAE participation, sex, age, and PTSD symptoms. The remaining β‐values indicate smaller effects of mTBI and MVAE on each of the HR‐QOL outcomes. It was beyond the scope of the present study to determine the true clinical relevance of these T‐score differences; however, this is an important area for future research to measure both the effects of mTBI history and participation in MVAE.

Limitations

This study had several limitations. The cross‐sectional design and use of self‐reported predictor and outcome measures prevents any assessment of causal relationships between our predictors and outcomes. Future research employing longitudinal and interventional methodologies would provide valuable insights into directionality and causality. Self‐reported measures may introduce bias to our study findings; however, we were unable to determine whether any present bias in self‐reported measures existed or how it might change the direction or size of observed effects in this study. In particular, we used a self‐reported measure of MVAE participation as opposed to objective measures of physical activities using a wearable sensor. Using only self‐reported activities might have introduced potential over‐ or underreporting of physical activities, thereby limiting the utility of this variable as a true measure of MVAE. Only the primary reported activity was used to allocate participants into MVAE participation groups, which limits the inferences that can be made regarding all exercise participation of these individuals. Specifically, participating in one or more secondary aerobic activities could influence overall MVAE group allocation, and our investigation did not address the potential benefits of engaging in low‐level aerobic or nonaerobic (eg, strength training) activities. Incorporating objective measures, such as activity monitoring devices or implementing exercise interventions, could address these limitations and improve data accuracy. This study was conducted within a specific U.S. military SMV population who had been combat deployed and consented to enroll in a study focused on long‐term brain health, which may limit the generalizability of the findings to the broader military and general populations in the United States and elsewhere. Further, participants in the parent study (LIMBIC‐CENC PLS) who had missing data were removed listwise from our analyses. We did not determine whether they were missing completely at random, and therefore we cannot determine whether there were certain characteristics or study sites that were related to the absence of any of the included variables. Additionally, in a recent paper with an overlapping sample, authors reported sex differences in concussion exposure characteristics such that a lower proportion of female SMVs sustained mTBI during combat deployment and from blast‐related mechanisms than their male counterparts. ¹⁰ Although sex was included as an important covariate in analyses for the present study, further work is required to more fully contextualize the potential unique and interactive effects of sex and mTBI exposure on the subjective outcomes measured in this study.

CONCLUSION

Participation in more frequent MVAE was associated with better functioning across most of the HR‐QOL domains included in this study. Greater lifetime exposure to mTBI was associated with worse HR‐QOL across all domains, but the effects of participation in MVAE activities on HR‐QOL outcomes was not dependent on mTBI history. There was also no clear association between mTBI history and participation in MVAE. Considered together, there are benefits for SMVs who engage in aerobic exercise, regardless of their mTBI history. Exercise, specifically MVAE, is a readily available modifiable behavior with numerous health benefits and should be part of a healthy lifestyle for combat‐exposed SMVs.

FUNDING INFORMATION

This work was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, through the Psychological Health/Traumatic Brain Injury Research Program Long‐Term Impact of Military‐Relevant Brain Injury Consortium (LIMBIC) Award/W81XWH‐18‐PH/TBIRP‐LIMBIC under Awards No. W81XWH1920067 and W81XWH‐13‐2‐0095, and by the US Department of Veterans Affairs Awards No. I01 CX002097, I01 CX002096, I01 HX003155, I01 RX003444, I01 RX003443, I01 RX003442, I01 CX001135, I01 CX001246, I01 RX001774, I01 RX 001135, I01 RX 002076, I01 RX 001880, I01 RX 002172, I01 RX 002173, I01 RX 002171, I01 RX 002174, and I01 RX 002170. The US Army Medical Research Acquisition Activity, 839 Chandler Street, Fort Detrick MD 21702‐5014 is the awarding and administering acquisition office. The study protocol was approved by the Virginia Commonwealth University Institutional Review Board in compliance with all applicable federal regulations governing the protection of human subjects, protocol number HM20002321. The views, opinions, interpretations, conclusions and recommendations expressed are those of the authors and do not necessarily reflect the official policy of the Department of the Navy, the Department of the Army, Department of Defense, Department of Veterans Affairs or the US Government.

DISCLOSURES

The authors declare that they have no competing interests.

Supporting information

Data S1. Supporting Information.

Casola BE, Hall MJ, Fraser JJ, et al. Associations among aerobic physical activity, mild traumatic brain injury history, and health‐related quality of life in military service members and Veterans: A LIMBIC‐CENC study. PM&R. 2026;18(1):33‐43. doi: 10.1002/pmrj.13436