Advanced brain age in deployment-related traumatic brain injury: A LIMBIC-CENC neuroimaging study

Dennis, Emily; Taylor, Brian; Newsome, Mary R.; Troyanskaya, Maya; Abildskov, Tracy J.; Betts, Aaron M.; Bigler, Erin D.; Cole, James H.; Davenport, Nicholas D.; Duncan, Timothy D.; Gill, Jessica; Guedes, Vivian A.; Hinds, Sidney; Hovenden, Elizabeth; Kenney, Kimbra; Pugh, Mary Jo; Scheibel, Randall S.; Shahim, Pashtun-Poh; Shih, Robert Y.; Walker, William C.; Werner, J. Kent; York, Gerald E.; Cifu, David X.; Tate, David F.; Wilde, Elisabeth A.

doi:10.1080/02699052.2022.2033844

Cited by 13 publications

(6 citation statements)

References 88 publications

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“…In contrast to others, 2,19,20 Cole and colleagues found little evidence of PAD in a single uncomplicated mild TBI event. On the other hand, a pronounced effect has been seen in cmsTBI.…”

Section: Injury Severity and Padmentioning

confidence: 61%

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi‐Cohort Mega‐Analysis

Dennis,

Vervoordt,

Adamson

et al. 2024

Annals of Neurology

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ObjectiveThe long‐term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain‐age estimation could provide a novel and efficient indexing of the long‐term consequences of TBI. Brain‐age procedures use predictive modeling to calculate brain‐age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression.MethodsThrough the ENIGMA Adult Moderate and Severe (AMS)‐TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross‐sectional T1w‐MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI.ResultsFindings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance.InterpretationThis work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024

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“…In contrast to others, 2,19,20 Cole and colleagues found little evidence of PAD in a single uncomplicated mild TBI event. On the other hand, a pronounced effect has been seen in cmsTBI.…”

Section: Injury Severity and Padmentioning

confidence: 61%

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi‐Cohort Mega‐Analysis

Dennis,

Vervoordt,

Adamson

et al. 2024

Annals of Neurology

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“…In contrast to others, 2,17,18 Cole and colleagues found little evidence of PAD in a single uncomplicated mild TBI event. On the other hand, a pronounced effect has been seen in cmsTBI.…”

Section: Injury Severity and Padmentioning

confidence: 61%

“…12 Brain age prediction modeling shows that, within the first several years after cmsTBI, there is increased atrophy in gray and white matter equivalent to about half a decade in chronological age in msTBI, [13][14][15][16] and 1-3 years in mild TBI. 2,17,18 The extent to which post-traumatic atrophy may evolve as individuals transition through various stages of life, continuing into senescence for years and even decades, remains to be established.…”

Section: Introductionmentioning

confidence: 99%

Accelerated Aging after Traumatic Brain Injury: an ENIGMA Multi-Cohort Mega-Analysis

Dennis,

Vervoordt,

Adamson

et al. 2023

Preprint

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Objective The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. In light of current evidence that even a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using MRI data. Complicated mild, moderate and severe TBI (cmsTBI) is associated with a higher predicted (brain) age difference (PAD), but the progression of PAD over time remains unclear. Here we sought to examine whether PAD increases as a function of time since injury (TSI). Methods As part of the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n=343), along with controls, for a total sample size of 540, to reproduce and extend prior findings in the study of TBI brain age. T1w-MRI data were aggregated across 7 cohorts and brain age was established using a similar brain age algorithm to prior work in TBI. Results Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find evidence supporting a link between PAD and cognitive performance. Interpretation This work provides evidence that changes in brain structure after msTBI are dynamic, with an initial period of change, followed by relative stability, eventually leading to further changes in the decades after a single msTBI.

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“…One view is that a higher BDA is an indicator of accelerated brain aging that has accumulated over an individual's lifetime [35]; another postulates that individuals vary in their brain and body health from the beginning of life [36, 37]. Both perspectives are supported by the results of empirical studies; perinatal variables (birth weight) and genetic variability are associated with BDA [36, 38], as well as unfavourable lifestyle factors: obesity, diabetes, alcohol consumption, traumatic brain injury, smoking, blood pressure [15, 26, 38–41].…”

Section: Discussionmentioning

confidence: 99%

Machine‐learning‐derived heart and brain age are independently associated with cognition

Iakunchykova

Schirmer

Vangberg

et al. 2023

Euro J of Neurology

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Background and purpose A heart age biomarker has been developed using deep neural networks applied to electrocardiograms. Whether this biomarker is associated with cognitive function was investigated. Methods Using 12‐lead electrocardiograms, heart age was estimated for a population‐based sample (N = 7779, age 40–85 years, 45.3% men). Associations between heart delta age (HDA) and cognitive test scores were studied adjusted for cardiovascular risk factors. In addition, the relationship between HDA, brain delta age (BDA) and cognitive test scores was investigated in mediation analysis. Results Significant associations between HDA and the Word test, Digit Symbol Coding Test and tapping test scores were found. HDA was correlated with BDA (Pearson's r = 0.12, p = 0.0001). Moreover, 13% (95% confidence interval 3–36) of the HDA effect on the tapping test score was mediated through BDA. Discussion Heart delta age, representing the cumulative effects of life‐long exposures, was associated with brain age. HDA was associated with cognitive function that was minimally explained through BDA.

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Advanced brain age in deployment-related traumatic brain injury: A LIMBIC-CENC neuroimaging study

Cited by 13 publications

References 88 publications

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi‐Cohort Mega‐Analysis

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi‐Cohort Mega‐Analysis

Accelerated Aging after Traumatic Brain Injury: an ENIGMA Multi-Cohort Mega-Analysis

Machine‐learning‐derived heart and brain age are independently associated with cognition

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