Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 1;8(8):e2525719.
doi: 10.1001/jamanetworkopen.2025.25719.

Vascular Risk Factors and 1-Year Cognitive Change Among Individuals With Traumatic Brain Injury

Andrea L C Schneider  1   2 , Katherine J Hunzinger  3 , Benjamin L Brett  4 , Danielle K Sandsmark  1 , Sonia Jain  5 , Xiaoying Sun  5 , Raquel C Gardner  6 , Geoffrey T Manley  7 , Ramon Diaz-Arrastia  1 , Lindsay D Nelson  4 ; TRACK-TBI Study Investigators; Patrick Belton  8 , Shawn Eagle  9 , Shankar Gopinath  10 , Ramesh Grandhi  11 , C Dirk Keene  12 , Vijay Krishnamoorthy  13 , Christine Mac Donald  12 , Michael McCrea  14 , Randall Merchant  15 , Pratik Mukherjee  16 , Laura B Ngwenya  17 , David Okonkwo  9 , Claudia Robertson  10 , David Schnyer  18 , Sabrina R Taylor  16 , John K Yue  16 , Ross Zafonte  19
Affiliations

Vascular Risk Factors and 1-Year Cognitive Change Among Individuals With Traumatic Brain Injury

Andrea L C Schneider et al. JAMA Netw Open. .

Abstract

Importance: Traumatic brain injury (TBI) and vascular risk factors are associated with cognitive impairment, but it is unknown if individuals with vascular risk factors experience worse cognitive outcomes after TBI.

Objective: To evaluate cognitive function among patients with TBI with vs without comorbid preinjury vascular risk factors.

Design, setting, and participants: This prospective cohort study examined individuals with TBI enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Study between February 26, 2014, and August 8, 2018, with a 1-year follow-up. Analyses were conducted February 26, 2024, to May 29, 2025.

Exposures: Vascular risk factors (ie, hypertension, diabetes, hyperlipidemia, and smoking).

Main outcomes and measures: Participants underwent a 5-test cognitive assessment at 2 weeks, 6 months, and 1 year postinjury; tests were combined into a global cognitive factor score in primary analyses and examined individually in secondary analyses. Inverse probability of attrition-weighted generalized estimating equations adjusted for age, sex, race, ethnicity, education, TBI severity, prior TBI, and psychiatric history were used to estimate the associations.

Results: The 1313 participants were a mean (SD) age of 38.7 (16.4) years, 428 were female (32.6%), 885 were male (67.4%), 393 had never smoked (29.9%), 221 had hypertension (16.8%), 98 had diabetes (7.5%), and 116 had hyperlipidemia (8.8%). Both participants with and without vascular risk factors had improvement in cognition over the first year postinjury. Compared with individuals without diabetes, participants with diabetes had lower global cognitive factor scores at 2 weeks postinjury (mean z-score difference, -0.25; 95% CI, -0.45 to -0.04), worse executive functioning at 2 weeks postinjury, and less improvement on processing speed over the first-year postinjury. There were no significant differences in cognitive performance comparing participants with vs without hypertension, hyperlipidemia, and smoking. Individuals with 2 or more vascular risk factors (compared with no vascular risk factors) had lower global factor score at 2 weeks postinjury (mean difference, -0.21; 95% CI, -0.19 to -0.07) and worse verbal episodic memory immediate recall, executive functioning, and processing speed at 2 weeks, but similar improvements in cognitive performance over the first-year postinjury.

Conclusions and relevance: In this cohort study of individuals with TBI, those with diabetes displayed poorer global cognitive function and executive functioning 2 weeks after TBI and recovered less in processing speed over the first-year postinjury. Given the modifiable nature of comorbid vascular risk factors, future work interrogating postinjury changes in vascular risk factor burden, over longer follow-up, is warranted.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Schneider reported receiving grant K23NS123340 from the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) and grant HT9425-23-1-0981 from the Department of Defense (DOD) during the conduct of the study and being an associate editor at Neurology from the American Academy of Neurology outside the submitted work. Dr Brett reported receiving grants from National Institutes of Aging and NINDS outside the submitted work. Dr Sandsmark reported receiving grants from BrainBox outside the submitted work. Dr Manley reported receiving grant U01NS086090 from NIH-NINDS and grants W81XWH-18-2-0042 and W81XWH-15-9-0001 from the DOD during the conduct of the study and assisting with Abbott Laboratories specimen collection for the evaluation of traumatic brain injury in adults and pediatrics and serving on the National Football League scientific advisory board outside the submitted work. Dr Diaz-Arrastia reported receiving grants and stock options from BrainBox Solutions, receiving nonfinancial support from MesoScale Discoveries, receiving consultant fees from Dompe USA, and receiving grants from Abbott outside the submitted work. Dr Nelson reported receiving grants from the DOD for unrelated TBI research, the US Centers for Disease Control and Prevention, the MCW Advancing a Healthier Wisconsin Endowment, and NIH and receiving consulting fees from Resolys Bio outside the submitted work. Dr McCrea reported receiving grants from NIH during the conduct of the study and receiving grants from Abbott and receiving consultant fees from Neurotrauma Sciences outside the submitted work. Dr Ngwenya reported receiving grants from Abbott and Biogen outside the submitted work. Dr Robertson receiving grants from Abbott Laboratories and serving on the National Football League scientific advisory board outside the submitted work. Dr Zafonte reported being a member of the scientific advisory board of Myomo and Nano Dx, editing the textbook Brain Injury Medicine, being the editor-in-chief of the Journal of Osteopathic Medicine, and serving on the Mackey White committee of the National Football League Players Association.

Figures

Figure 1.
Figure 1.. Patterns of Vascular Risk Factors in the Study Population
Figure 2.
Figure 2.. Mean (95% CI) for Cognitive Performance (Global Cognitive Factor Score) at 2 Weeks, 6 Months, and 1 Year Postinjury by Vascular Risk Factor Status
See this image and copyright information in PMC

References

    1. Nelson LD, Temkin NR, Dikmen S, et al. ; and the TRACK-TBI Investigators . Recovery after mild traumatic brain injury in patients presenting to US level I trauma centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. JAMA Neurol. 2019;76(9):1049-1059. doi: 10.1001/jamaneurol.2019.1313 - DOI - PMC - PubMed
    1. McCrea MA, Giacino JT, Barber J, et al. ; TRACK-TBI Investigators . Functional outcomes over the first year after moderate to severe traumatic brain injury in the prospective, longitudinal TRACK-TBI study. JAMA Neurol. 2021;78(8):982-992. doi: 10.1001/jamaneurol.2021.2043 - DOI - PMC - PubMed
    1. Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing commission. Lancet. 2024;404(10452):572-628. doi: 10.1016/S0140-6736(24)01296-0 - DOI - PubMed
    1. Knopman DS, Gottesman RF, Sharrett AR, et al. Midlife vascular risk factors and midlife cognitive status in relation to prevalence of mild cognitive impairment and dementia in later life: The Atherosclerosis Risk in Communities Study. Alzheimers Dement. 2018;14(11):1406-1415. doi: 10.1016/j.jalz.2018.03.011 - DOI - PMC - PubMed
    1. Sandsmark DK, Bashir A, Wellington CL, Diaz-Arrastia R. Cerebral microvascular injury: a potentially treatable endophenotype of traumatic brain injury-induced neurodegeneration. Neuron. 2019;103(3):367-379. doi: 10.1016/j.neuron.2019.06.002 - DOI - PMC - PubMed