Associations Between Prior Head Injury, Physical Functioning, and Frailty in the Atherosclerosis Risk in Communities Study

Abstract

Background

Older adults have the highest rates of head injury and are at the greatest risk for subsequent dysfunction, yet research on subsequent physical decline is limited. We sought to examine cross-sectional and prospective associations of head injury with physical functioning and frailty among older adults.

Methods

A total of 5 598 Atherosclerosis Risk in Communities Study participants from Visit 5 (2011–13) underwent assessments of physical functioning (Short Physical Performance Battery [SPPB], comprised of gait speed, chair stands, and balance) and frailty (defined using established criteria) were followed through Visit 7 (2018–19). Head injury was self-reported or based on ICD-9 codes. Adjusted linear and multinomial logistic regression models were used to estimate associations. Prospective models incorporated inverse probability of attrition weights to account for death or attrition.

Results

Participants were a mean age of 75 years, 58% were women, 22% were Black, and 27% had a prior head injury. Compared to individuals without head injury, individuals with head injury had worse physical functioning (SPPB total score, β-coefficient = −0.22, 95% CI: −0.35 to −0.09) and were more likely to be pre-frail (OR = 1.19, 95% CI: 1.04 to 1.35) or frail (OR = 1.40, 95% CI: 1.08 to 1.80) compared to robust. Prospectively, head injury was associated with a 0.02 m/s greater decline (95% CI: −0.04 to −0.01) in gait speed over a median of 5 years. Among baseline robust individuals (n = 1 847), head injury was associated with increased odds of becoming pre-frail (OR = 1.32, 95% CI: 1.04 to 1.67) or frail (OR = 1.92, 95% CI: 1.05 to 3.51) compared to robust.

Conclusions

Older adults with prior head injury had worse physical functioning and greater frailty at baseline and were more likely to become frail and walk slower over time, compared to individuals without head injury.

Traumatic brain injury (TBI), or head injury, is an injury caused by any force to the head which results in neurologic symptoms. It is increasingly recognized that the sequelae of TBI are long-lasting and associated with significant disability and mortality (1–4). Head injury rates are highest among older adults (aged 65+ years), where falls are the leading cause of head injury (5). Older adults also commonly experience age-related physical and cognitive decline (6). It is possible that head injury may compound age-related changes in physical and cognitive function. Therefore, it is important to investigate the relationship between head injury and physical functioning and frailty in aging populations (3,7).

Previous research has shown physical functioning differences between adults with and without head injury, but prior work has been largely limited to subjective outcomes and short follow-up (ie, ≤2 years) (6,8,9). Gait, which is a strong indicator of physical functioning, has been shown to be associated with postural control impairments up to 2 years post-TBI among younger individuals. However, gait impairments are less well-characterized among older adults with head injuries (9–14). Furthermore, frailty, which is a result of physiological decline across multiple domains, increases with age, placing older adults at risk for subsequent physical dysfunction and morbidity (15). Indeed, recent work has shown that individuals with TBI who are frail have unfavorable outcomes compared to robust individuals with TBI (7). Because older adults are at risk for age-related physical function decline and frailty, both of which may be exacerbated by head injury, it is important to investigate associations of head injury with the objectively measured outcomes of physical functioning and frailty in aging populations to better inform prevention strategies and clinical management of TBI in older adults.

Herein, we utilized data from the ongoing community-based Atherosclerosis Risk in Communities (ARIC) Study to investigate the cross-sectional (ARIC Visit 5, 2011–13) and prospective (ARIC Visits 5 [2011–13], Visit 6 [2016–17], Visit 7 [2018–19]) associations between prior head injury and physical function and frailty. We hypothesized that individuals with prior head injury would have worse physical functioning and greater prevalence of frailty cross-sectionally and would be prospectively associated with greater declines in physical function and risk of frailty compared to individuals with no prior head injury.

Method

Study Design and Population

The ARIC Study is an ongoing cohort study comprised of community-dwelling individuals recruited from 4 locations in the United States (Forsyth County, North Carolina; Jackson, Mississippi; greater Minneapolis, Minnesota; and Washington County, Maryland) (16,17). Minneapolis, Minnesota, and Washington County, Maryland recruited mainly White participants, and Forsyth County, North Carolina recruited mainly White and Black participants, based on probability sampling of these communities, and by design, Jackson, Mississippi recruited only Black participants. Participants were enrolled between 1987 and 1989 when they were between 45 and 64 years of age and they have subsequently attended in-person visits. Herein, the baseline for analysis was ARIC Visit 5 (2011–13) as it was the first in-person visit where physical functioning and frailty were assessed. In total, 6 538 participants attended Visit 5. We excluded 44 participants of Asian or Indian or of Black at the Minnesota or Maryland field centers due to small numbers and race/center aliasing, 86 participants missing frailty data, 726 participants missing physical functioning data, and 84 participants missing data on statistical model covariates, resulting in 5 598 included participants. The study design and patterns of subsequent visits (Visit 6 [2016–17] and Visit 7 [2018–19]) attendance are shown in Figure 1.

The ARIC study was approved by the Institutional Review Boards at each participating institution and all participants (or their legally authorized representatives) provided written informed consent at each attended study visit.

Head Injury

Consistent with prior studies (4,18–20), the presence or absence of a prior head injury at Visit 5 (2011–13) was defined using a combination of self-reported data and International Classification of Diseases, Ninth Revision (ICD-9) code data (Supplementary Table 1). Self-reported head injury data was obtained from all participants at ARIC Visit 3 (1993–95) and 4 (1996–98) and from a subset of participants at the Brain MRI Study (2004–06) and at ARIC Visit 5 (2011–13). The self-reported data included questions about prior head injury requiring physician care, association with loss of consciousness, the number of prior head injuries, and the year of head injury. ICD-9 code data from hospitalizations was sourced from continuously collected ARIC Study hospitalization surveillance (starting in 1987) and linked Centers for Medicare and Medicaid Services (CMS) Fee-for-Service (FFS) data (starting in 1991 for enrolled individuals aged 65+ years) and data from emergency department encounters came from linked CMS FFS data. The ICD-9 code definition for head injury is consistent with the Centers for Disease Control and Prevention (CDC) case definition for traumatic brain injury (21–23).

As secondary exposures, we considered the time between the first head injury and ARIC Visit 5 (stratified analyses: <10 years versus no head injury; ≥10 years versus no head injury), the number of prior head injuries (0; 1; 2+), and head injury severity (none; mild; moderate/severe/penetrating) defined using the Department of Defense criteria among the subset of individuals with prior head injuries identified using ICD-9 code data (24). In sensitivity analyses, we separately considered head injuries identified by self-report versus by ICD codes.

Physical Functioning

Physical functioning was assessed using the Short Physical Performance Battery (SPPB) (25,26) at ARIC Visit 5 (2011–13), Visit 6 (2016–17), and Visit 7 (2018–19). The SPPB consists of 3 tasks: gait speed (4-m walk), time to complete 5 chair stands, and balance (ability to maintain standing balance side-by-side, semi-tandem, and tandem positions for up to 10 seconds). Each of the 3 tasks is scored 0 (worst) to 4 (best); the 3 components are summed for a SPPB total possible score with range of 0–12. SPPB scores were considered categorically (low physical function defined as ≤2 for component scores or ≤6 for SPPB total) and continuously. For purposes of clinical interpretability, we also analyzed SPPB 4-meter walk performance as a function of gait speed (m/s), whereby greater gait speeds indicate better physical functioning.

Frailty

Participants were categorized as frail, pre-frail, or robust (ie, not frail) at ARIC Visit 5 (2011–13), Visit 6 (2016–17), and Visit 7 (2018–19) using a phenotypic frailty construct (27) previously validated in the ARIC cohort (28,29) based on the following characteristics: 1) unintentional weight loss of >10% between Visits 4 and 5 or body mass index (BMI) < 18.5 kg/m²; 2) <20th percentile in sex-specific Baeke leisure sport activity index (30); 3) <20th percentile in sex- and height-adjusted walking speed using established thresholds; 4) responded “some of the time” or “most of the time” to questions on fatigue and exhaustion on the Center for Epidemiologic Studies Depression Scale (CES-D) (31); and 5) <20th percentile in sex- and BMI-specific dominant hand grip strength using established thresholds (26). Participants were classified as frail if 3 or more of the components were present, pre-frail if 1–2 of the components were present, and robust if none of the components were present.

Covariates

Covariates included in statistical models were collected at ARIC Visit 5 (2011–13) with the exception of education and race, which were self-reported at ARIC Visit 1 (1987–89). All covariates were selected a priori due to their associations with both head injury and physical functioning and/or frailty. Covariates included in both physical functioning and frailty models: age (years; continuous), sex (men; women), race/center (Minnesota White; Maryland White; North Carolina White; North Carolina Black; Mississippi Black), education (<high school; high school, GED or vocational school; some college, college, graduate, or professional school), cigarette smoking (current; former; never), alcohol consumption (current; former; never), military veteran status (yes; no), hypertension (yes; no), diabetes (yes; no), and cognitive status (defined by an adjudication algorithm as normal; mild cognitive impairment; dementia) (32). In models for physical functioning, additional covariates included BMI (kg/m²; continuous), physical activity (Baeke leisure sport activity index; continuous) (30), and depression (defined by CES-D score ≥9) (31); of note, these 3 variables are already included in the definition of frailty, so are not included in the statistical models for frailty.

Statistical Analysis

Participants’ characteristics are shown overall and stratified by head injury status using means and standard deviations for continuous variables and numbers and proportions for categorical variables. Participant characteristics are also shown by comparing individuals with baseline (ARIC Visit 5, 2011–13) and follow-up (ARIC Visit 6, 2016–17 and/or ARIC Visit 7, 2018–19) data to individuals with baseline (ARIC Visit 5, 2011–13) data only.

The age-adjusted prevalence of poor physical function (total score ≤6 and component score ≤2) (33) and of pre-frailty/frailty at Visit 5 was calculated using logistic regression models. To examine the adjusted cross-sectional associations between prior head injury and physical function at Visit 5, adjusted linear regression models were used, with evaluation for the possibility of multicollinearity performed using the variance inflation factor. Adjusted multinomial logistic regression models were used to estimate the adjusted association of head injury with pre-frailty and frailty. To estimate the adjusted prospective associations between head injury and physical function change (measured at Visits 5, 6, and 7), adjusted generalized estimating equations (GEE) models with linear splines for time with a knot at 5 years (median time between Visits 5 and 6), unstructured covariance, and random intercept were used. Among individuals who were robust at ARIC Visit 5, adjusted multinomial logistic regression models were used to estimate the adjusted association of head injury with the development of pre-frailty and frailty at Visits 6 and/or 7.

In our primary prospective analyses, inverse probability of attrition weighting (IPAW) (34,35) was used to account for death and study attrition, making all prospective results presented herein representative of the included Visit 5 (baseline) participants (not only the subset of participants who attended Visits 6 and 7). The inverse probability of attrition weights created was proportional to the inverse of the probability of physical function and frailty measure completion (at Visits 6 and 7 separately) and standardized so that the sum of the weights equaled the number of participants with complete outcome data. Variables included in the IPAW models were covariates included in the statistical models (age, sex, race/center, education, cigarette smoking status, alcohol consumption, depression, cognitive status, BMI, and physical activity), and Visit 5 frailty and SPPB scores. In secondary prospective analyses, we additionally present unweighted (complete case) models.

All analyses were performed using Stata MP (Version 17, StataCorp, College Station, TX), and a p value of <.05 was considered statistically significant.

Results

At baseline (Visit 5, 2011–13), the mean age of participants was 75.4 years, 58.0% were women, 21.8% were Black, and 27.4% had a history of head injury (Table 1). The median time between first head injury and ARIC Visit 5 was 32.2 years (25th–75th percentile = 14.5–58.2). Compared to those without a history of head injury, individuals with a history of head injury were slightly older, were more likely to be men, of the White, and were more likely to have mild cognitive impairment or dementia and depression. Participants with only baseline (Visit 5) data were similar to participants with both baseline and follow-up data in terms of sex, and race, but were older, less likely to have greater than high school education, more likely to have a prior head injury and mild cognitive impairment or dementia, had lower SPPB scores, and were more likely to be frail or pre-frail at Visit 5 (Supplementary Table 2).

The age-adjusted prevalence of low SPPB total score (≤6) and of pre-frailty/frailty at Visit 5 was higher among individuals with prior head injury compared to those without head injury (Figure 2). In fully adjusted models, prior head injury was cross-sectionally associated with lower SPPB total score (β-coefficient = −0.22, 95% CI: −0.35 to −0.09), lower component scores (balance: β-coefficient = −0.07, 95% CI: −0.13 to −0.01; gait speed: β-coefficient = −0.06, 95% CI: −0.10 to −0.02; chair stand: β-coefficient = −0.09, 95% CI: −0.16 to −0.02), and slower gait speed (β-coefficient = −0.02 m/s, 95% CI: −0.03 to −0.01; Table 2). Head injury history was also associated with increased odds of being prefrail (OR = 1.19, 95% CI: 1.04 to1.35) and frail (OR = 1.40, 95% CI: 1.08 to 1.80) compared to robust (Table 3).

Over a median of 5 years, there was no association of prior head injury with greater decline in physical functioning on the SPPB in unweighted analyses. In analyses incorporating IPAW weights, participants with head injury had 0.11 (95% CI: −0.21 to 0.00) points more decline in gait speed and a 0.02 m/s (95%CI: −0.04 to −0.01) greater decline in gait speed compared to participants without head injury (Table 2). Among participants who were robust at Visit 5 (n = 1 847), individuals with head injury were more likely to become pre-frail (OR = 1.32, 95% CI: 1.04 to 1.67) or frail (OR = 1.92, 95% CI: 1.05 to 3.51), compared to robust, at Visit 6 and/or Visit 7 (Table 3).

In secondary analyses of more recent (<10 years) head injuries, results were consistent with our main analyses. Results of analyses of less recent (≥10 years) head injury were also consistent with the main analyses, but cross-sectional associations with pre-frailty and frailty were attenuated (Supplementary Tables 3 and 4). In analyses of a number of head injuries with physical functioning, 2+ prior head injuries, but not 1 prior head injury, were associated with worse cross-sectional performance on the SPPB total and component scores and gait speed, but not longitudinal performance (Supplementary Table 5). There was no evidence of a dose-response association of a number of head injuries with frailty (Supplementary Table 6). Analyses of head injury severity were limited by small numbers of moderate/severe/penetrating head injury (n = 63), but mild head injury was associated with worse cross-sectional, but not longitudinal, performance on the SPPB (Supplementary Table 7). There was no evidence of a dose-response association of head injury severity with frailty (Supplementary Table 8). In sensitivity analyses, self-reported head injury was not cross-sectionally or prospectively associated with SPPB performance but was significantly associated with the prospective decline in gait speed (m/s) and with the development of frailty. In contrast, ICD-code-defined head injury was cross-sectionally associated with worse performance on the SPPB, gait speed, and frailty, but there were no significant prospective associations (Supplementary Tables 9 and 10).

Discussion

In this community-dwelling population, older adults with prior head injury had worse physical functioning and greater frailty at baseline, compared to individuals without head injury. Among individuals who were robust at baseline, individuals with prior head injury were more likely to become frail over time. Individuals with prior head injury also had a greater decline in gait speed over a median of 5-years follow-up, compared to individuals without head injury. Future studies are needed to determine if older adults with a history of head injury may benefit from targeted measures focused on improving physical functioning and prevention of frailty.

Head injury in younger populations has been associated with physical dysfunction and alterations in gait, including gait speed reductions (1–3,9). Our study expands this work to older populations by providing evidence that individuals with prior head injury are more likely to have poor physical functioning and frailty both cross-sectionally and prospectively. Previous studies have shown that frail individuals are more likely to fall and suffer a TBI and are more likely to have worse outcomes after TBI (6,7). In the context of prior literature, our work supports a bi-directional relationship between head injury with physical functioning and frailty.

Although head injury was associated with worse performance on the SPPB total and component scores cross-sectionally, individuals with a history of head injury had small, but statistically significantly greater declines in gait speed over time compared to those without a history of head injury. It is important to note that most results were close but did not meet previously established criteria for clinically meaningful changes in SPPB total score (0.27–0.55 points) or gait speed (0.04–0.06 m/s) (36,37) Our findings are consistent with previous research which reported more conservative gait and reduced gait speed following TBI (38,39). It is important to note that previous research on the association of TBI with gait speed has been largely limited to smaller samples (n < 50), younger cohorts (<50 years old), and shorter follow-up time (≤2 years post-injury) (38,39). In our study, the median time from first head injury to the first physical functioning and frailty assessment was 32.2 years, suggesting that the long-term physical function-related sequelae of a head injury may persist for decades after the acute injury. Supporting this notion, in our secondary analyses, associations of less recent (occurring ≥10 years prior to baseline assessment) head injury with physical functioning and frailty were largely consistent with our main analyses. Furthermore, individuals with head injury occurring ≥10 years prior to baseline assessment were more likely to become pre-frail or frail over study follow-up. Importantly, in our prospective analyses, we used inverse probability of attrition weighting methods to account for death and study attrition, which were more likely among both individuals with a prior head injury and among individuals with worse physical functioning and greater frailty at baseline (40). Overall, our findings likely reflect a combination of the long-term sequelae of head injury and age-related physical and cognitive declines (36,41–43).

Unlike the statistically significant declines in gait speed over time, this study did not show significant differences in SPPB chair stand or balance scores between head injury groups. The lack of differences may partially be explained by the varying difficulty level of the tasks. The balance task is comprised of static postural control tasks, which have been shown to not be sensitive enough to detect physical performance impairments associated with neurotrauma (38,44). Moreover, the repeated chair stand task is a measure of lower-leg strength and not an indicator of more complex neurological functioning, which may explain why there were no group differences for declines in chair stand performance over time when accounting for age and other confounders (25,26,45). Overall, our findings generally support that the functional impairments of chronic head injury are most significant for tasks that require executive functioning, such as gait speed (44).

Our sample included older participants of self-reported White or Black from 4 distinct communities across the United States, and as such, may not be generalizable to other age and race groups. Second, head injury was defined via self-report and/or ICD-9 codes, which may have resulted in under-reporting and/or misclassification of injury, particularly for mild head injuries. Moreover, a detailed description of the injury (ie, mechanism) and other factors related to neurotrauma history (eg, sport/contact sport participation history) were not available. However, this definition has been used previously in the ARIC study (18,46), and self-reporting has been shown to be a reliable method of ascertaining lifetime TBI exposure even among individuals with cognitive impairment (47). Furthermore, the ICD-9 codes used are consistent with the CDC TBI surveillance definition (21,22). Similarly, the SPPB is an established assessment of physical functioning in older populations (25,26) and the definition of frailty was based on a validated and widely used definition (16,17,48). Future research in diverse populations of older adults with detailed injury characteristics and physical functioning assessments is warranted.

In conclusion, in this sample of community-dwelling older adults, prior head injury was associated with worse physical functioning and greater frailty both cross-sectionally and over a median of 5 years follow-up, compared to no head injury. These findings suggest that a history of head injury may be a modifiable risk factor for functional decline and frailty among older individuals. Future studies are needed to investigate the impact of targeted interventions on preventing head injury and/or improving physical functioning in older adults, in addition to focused efforts toward the prevention of frailty among older individuals with a history of head injury.

Funding

The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). The ARIC Neurocognitive Study is supported by U01HL096812, U01HL096814, U01HL096899, U01HL096902, and U01HL096917 from the National Institutes of Health (National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Institute on Aging, and National Institute on Deafness and Other Communication Disorders). K.J.H. and A.E.W. were supported by the National Institute of Neurological Disorders and Stroke T32NS043126. A.L.C.S. was supported by the National Institute of Neurological Disorders and Stroke K23NS123340. R.F.G. was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program. B.G.W. was supported by R01AG054787.

Conflict of Interest

None.

Acknowledgments

We thank the staff and participants of the ARIC study for their important contributions.

Author Contributions

K.J.H. and A.L.C.S. were involved in the study of concept and design. All authors were involved in ARIC data request proposal. K.J.H., A.E.W., and A.L.C.S. were involved in data analysis and interpretation. All authors were involved in manuscript preparation and approved the final version of the manuscript.

References