Objective

While traumatic brain injury (TBI) is common across the life span, the detailed neurobehavioral characteristics of older adults with prior TBI remain unclear. Our goal was to compare the clinical profile of older independently living veterans with and without prior TBI.

Setting

Two veterans' retirement communities.

Participants

Seventy-five participants with TBI and 71 without (mean age = 78 years).

Design

Cross-sectional.

Main measures

TBI history was determined by the Ohio State University TBI Questionnaire. We assessed psychiatric and medical history via interviews and chart review and conducted measures assessing functional/lifestyle, psychiatric, and cognitive outcomes. Regression analyses (adjusted for demographics, diabetes, prior depression, substance abuse, and site) were performed to compare between TBI and non-TBI participants.

Results

Compared with veterans without TBI, those with TBI had greater functional impairment (adjusted P = .05), endorsed more current depressive (adjusted P = .04) and posttraumatic stress disorder symptoms (adjusted P = .01), and had higher rates of prior depression and substance abuse (both adjusted Ps < .01). While composite memory and language scores did not differ between groups, participants with TBI performed worse on tests of executive functioning/processing speed (adjusted P = .01).

Conclusions

Our results suggest that TBI may have adverse long-term neurobehavioral consequences and that TBI-exposed adults may require careful screening and follow-up.

Background

Traumatic brain injury (TBI) has been identified as a risk factor for Parkinson's disease (PD). Motor dysfunction among TBI-exposed elders without PD has not been well characterized. We sought to determine whether remote TBI is a risk factor for motor dysfunction on exam and functionally relevant motor dysfunction in day-to-day life among independently living elders without PD.

Methods

This is a cross-sectional cohort study of independently living retired military veterans aged 50 or older with (n = 78) and without (n = 85) prior TBI-all without diagnosed PD. To characterize multidimensional aspects of motor function on exam, the Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination was performed by a board-certified neurologist and used to calculate a modified UPDRS (mUPDRS) global motor score and four domain scores (tremor, rigidity, bradykinesia, and posture/gait). Functionally relevant motor dysfunction was assessed via self-report of falls within the past year.

Results

In analyses adjusted for demographics and comorbidities that differed between groups, compared with veterans without TBI, those with moderate-to-severe TBI were more likely to have fallen in past year (33% vs. 14%, risk ratio 2.5 [95% confidence interval 1.1-5.4]), had higher (worse) mUPDRS global motor (p = .03) and posture/gait scores (p = .02), but not higher tremor (p = .70), rigidity (p = .21), or bradykinesia scores (p = .22). Mild TBI was not associated with worse motor function.

Conclusions

Remote moderate-to-severe TBI is a risk factor for motor dysfunction-defined as recent falls and impaired posture/gait-among older veterans. TBI-exposed older adults may be ideal candidates for aggressive fall-screening and prevention strategies.

To identify long-term effects of traumatic brain injury (TBI) on levels of plasma neuron-derived exosome (NDE) protein biomarkers of cognitive impairment (CI), plasmas were obtained from four groups of older veterans, who were matched for age and sex: no TBI or CI (n = 42), no TBI with CI (n = 19), TBI without CI (n = 21), and TBI with CI (n = 26). The TBI was sustained 12 to 74 years before the study in 75%. The NDEs were enriched by sequential precipitation and anti-L1CAM antibody immunoabsorption, and extracted protein biomarkers were quantified by enzyme-linked immunosorbent assays. Chronic NDE biomarkers known to increase for three to 12 months after TBI, including cellular prion protein (PrPc), synaptogyrin-3, P-T181-tau, P-S396-tau, Aβ42, and interleukin (IL)-6, were elevated significantly in subjects who had TBI and CI compared with controls with TBI but no CI. Chronic NDE biomarker levels in subjects without TBI showed significantly higher levels of PrPc, synaptogyrin-3, P-T181-tau, and Aβ42, but not P-S396-tau and IL-6, in those with CI compared with controls without CI. The acute NDE biomarkers claudin-5, annexin VII, and aquaporin-4 were not increased in either group with CI. The NDE biomarkers P-S396-tau and IL-6, which are increased distinctively with CI after TBI, may prove useful in evaluating CI in older patients. Aβ42 and P-tau species, as well as their respective putative receptors, PrPc and synaptogyrin-3, remain elevated for decades after TBI and may mediate TBI-associated CI and be useful targets for development of drugs.

Objective

To determine the prevalence and types of cognitive impairment in a sample of nondemented participants aged ≥90 (the oldest-old) and to examine the relationships between cognitive impairment and cardiovascular risk factors.

Participants

The participants were 420 nondemented individuals from The 90+ Study, a study of aging and dementia in the oldest-old. These participants were categorized into four nonoverlapping groups: normal cognition, amnestic mild cognitive impairment (aMCI), nonamnestic MCI (naMCI), and other cognitive impairment (OCI). History of cardiovascular risk factors was assessed through self-report.

Results

The overall prevalence of cognitive impairment in nondemented participants was 34.0% (95% CI: 29.5-38.5). The prevalence of OCI was highest (17.4%; 95% CI: 13.9-21.4), followed by aMCI (8.3%; 95% CI: 5.9-11.4) and naMCI (8.3%; 95% CI: 5.9-11.4). Normal cognition was present in 66.0% (95% CI: 61.2-70.5) of participants. History of hypertension and stroke were the only risk factors that varied between the groups, occurring more frequently in participants with naMCI (χ(2) = 3.82; P < .05) and OCI (χ(2) = 5.51; P < .05).

Conclusions

This study found a high prevalence of cognitive impairment in a sample of nondemented oldest-old. We did not find a strong relationship between cardiovascular risk factors and the cognitive impairment groups, other than between hypertension and naMCI and stroke and OCI. Future studies comparing the incidence of dementia in these groups will ultimately determine their predictive utility in the oldest-old.

Objective

To test the hypothesis that veterans with traumatic brain injury (TBI) have an increased subsequent risk of sleep disorders, we studied the longitudinal association between TBI and incident sleep disorders in nearly 200,000 veterans.

Methods

We performed a cohort study of all patients diagnosed with a TBI in the Veterans Health Administration system from October 1, 2001, to September 30, 2015, who were age-matched 1:1 to veterans without TBI. Veterans with prevalent sleep disorders at baseline were excluded. Development of sleep disorders was defined as any inpatient or outpatient diagnosis of sleep apnea, hypersomnia, insomnia, or sleep-related movement disorders based on ICD-9 codes after the first TBI diagnosis or the random selection date for those without TBI. We restricted the analysis to those with at least 1 year of follow-up. We used Cox proportional hazards models to examine the association between TBI and subsequent risk of sleep disorders.

Results

The study included 98,709 veterans with TBI and 98,709 age-matched veterans without TBI (age 49 ± 20 years). After an average follow-up of 5 (1-14) years, 23,127 (19.6%) veterans developed sleep disorders. After adjustment for demographics, education, income, and medical and psychiatric conditions, those who had TBI compared to those without TBI were 41% more likely to develop any sleep disorders (hazard ratio 1.41 [95% confidence interval 1.37-1.44]), including sleep apnea (1.28 [1.24-1.32]), insomnia (1.50 [1.45-1.55]), hypersomnia (1.50 [1.39-1.61]), and sleep-related movement disorders (1.33 [1.16-1.52]). The association was stronger for mild TBIs, did not differ appreciably by presence of posttraumatic stress disorder, and remained after a 2-year time lag.

Conclusion

In 197,418 veterans without sleep disorders, those with diagnosed TBI had an increased risk of incident sleep disorders over 14 years. Improved prevention and long-term management strategies for sleep are needed for veterans with TBI.

Objective

To investigate whether sex and race differences exist in dementia diagnosis risk associated with traumatic brain injury (TBI) among older veterans.

Methods

Using Fine-Gray regression models, we investigated incident dementia diagnosis risk with TBI exposure by sex and race.

Results

After the exclusion of baseline prevalent dementia, the final sample (all veterans ≥55 years of age diagnosed with TBI during the 2001-2015 study period and a random sample of all veterans receiving Veterans Health Administration care) included nearly 1 million veterans (4.3% female; 81.8% White, 11.5% Black, and 1.25% Hispanic), 96,178 with TBI and 903,462 without TBI. Compared to those without TBI, Hispanic veterans with TBI were almost 2 times more likely (17.0% vs 10.3%; hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.51-2.01), Black veterans with TBI were >2 times more likely (11.2% vs 6.4%; HR 2.15, 95% CI 2.02-2.30), and White veterans with TBI were nearly 3 times more likely to receive a dementia diagnosis (12.0% vs 5.9%; HR 2.71, 95% CI 2.64-2.77). A significant interaction between TBI and race for dementia diagnosis was observed (p < 0.001). Both male and female veterans with TBI were more than twice as likely (men 11.8% vs 5.9%, HR 2.60, 95% CI 2.54-2.66; women 6.3% vs 3.1%, HR 2.36, 95% CI 2.08-2.69) to receive a diagnosis of dementia compared to those without. There was a significant interaction effect between sex and TBI (p = 0.02), but the magnitude of differences was small.

Conclusions

In this large, nationwide cohort of older veterans, all race groups with TBI had increased risk of dementia diagnosis, but there was an interaction effect such that White veterans were at greatest risk for dementia after TBI. Further research is needed to understand the mechanisms for this discrepancy. Differences in dementia diagnosis risk for men and women after TBI were significant but small, and male and female veterans had similarly high risks of dementia diagnosis after TBI.

Objective

Traumatic brain injury (TBI) is associated with elevated rates of cardiovascular disease (CVD), and both CVD and TBI are risk factors for dementia. We investigated whether CVD and its risk factors underlie the association between TBI and dementia.

Materials and methods

Cox proportional hazards models among 195,416 Veterans Health Administration patients age 55+ with TBI and a non-TBI, age/sex/race-matched comparison sample.

Results

Veterans +TBI were more likely to have any CVD diagnosis (24% vs 36% p = <0.001) or risk factor (83 vs. 90% p < .001) compared to -TBI. During follow-up (mean ~7 years), 12.0% of Veterans with TBI only (HR: 2.17 95% CI 2.09-2.25), and 10.3% with CVD only developed dementia (HR 1.21 95% CI 1.15-1.28), compared to 6.5% with neither. There was an additive association between TBI and CVD on dementia risk (HR 2.51, 95% CI 2.41-2.61). Among those +TBI (±CVD), risk was minimally attenuated by adjustment for CVD/CVD risk factors (unadjusted HR: 2.38, 95% CI: 2.31-2.45; adjusted HR: 2.17, 95% CI 2.10-2.23).

Conclusions

Older veterans TBI have increased prevalence of CVD/CVD risk factors. TBI and CVD had an additive statistical association, with dementia risk increased by ~2.5-fold. However, CVD accounted for little of the association between TBI and dementia. More research is needed to understand mechanisms of TBI-dementia and inform clinical guidelines post-TBI.

Objective

To determine whether blood-based biomarkers can differentiate older veterans with and without traumatic brain injury (TBI) and cognitive impairment (CogI).

Methods

We enrolled 155 veterans from 2 veterans' retirement homes: 90 without TBI and 65 with TBI history. Participants were further separated into CogI groups: controls (no TBI, no CogI), n = 60; no TBI with CogI, n = 30; TBI without CogI, n = 30; and TBI with CogI, n = 35. TBI was determined by the Ohio State University TBI Identification Method. CogI was defined as impaired cognitive testing, dementia diagnosis, or use of dementia medication. Blood specimens were enriched for CNS-derived exosomes. Proteins (neurofilament light [NfL], total tau, glial fibrillary acidic protein [GFAP], α-synuclein, β-amyloid 42 [Aβ42], and phosphorylated tau [p-tau]) and cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-10) were measured using ultrasensitive immunoassays.

Results

Veterans were, on average, 79 years old. In participants with TBI history, 65% had mild TBI; average time from most recent TBI was 37 years. In adjusted analyses, the TBI and CogI groups differed on CNS-enriched exosome concentration of p-tau, NfL, IL-6, TNF-α (all p < 0.05), and GFAP (p = 0.06), but not on Aβ42 or other markers. Adjusted area under the curve (AUC) analyses found that all significantly associated biomarkers combined separated TBI with/without CogI (AUC, 0.85; 95% confidence interval [CI], 0.74-0.95) and CogI with/without TBI (AUC, 0.88; 95% CI, 0.77-0.99).

Conclusions

Increased levels of blood-based, CNS-enriched exosomal biomarkers associated with TBI and CogI can be detected even decades after TBI.

Classification of evidence

This study provides Class II evidence that in veterans with a history of TBI, CNS-enriched exosome concentration of p-tau, NfL, IL-6, and TNF-α are associated with CogI.