Preliminary Investigation of Cerebral Blood Flow and Amyloid Burden in Veterans With and Without Combat-Related Traumatic Brain Injury

Ponto, Laura L. Boles; Brashers-Krug, Thomas; Pierson, Ronald; Menda, Yusuf; Ación, Laura; Watkins, G. Leonard; Sunderland, John; Koeppel, Julie A.; Jorge, Ricardo E.

doi:10.1176/appi.neuropsych.15050106

Cited by 18 publications

(20 citation statements)

References 40 publications

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“…19,[21][22][23] Briefly, all imaging was performed on an ECAT EXACT HR+Scanner (Siemens Medical Solutions USA, Inc, Knoxville, TN). Dynamic imaging (5 s/frame×20 frames) and arterial blood sampling commenced at tracer injection (45-50 mCi per injection) and continued for 100 seconds.…”

Section: Pet Imagingmentioning

confidence: 99%

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans

DuBose¹,

Ponto²,

Moser³

et al. 2018

Hypertension

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Abstract-Greater aortic stiffness and pulse pressure are associated with cerebrovascular remodeling, reduced white matter microstructure, and cognitive performance with aging in humans. However, it is unclear whether aortic stiffness and pulse pressure are associated with reduced basal global cerebral blood flow (CBF) and cerebrovascular reserve among older adults. Global CBF was quantified in 205 adults (range, 19-87 years; mean±SE: 30.6±1.3 years) using quantitative [ 15 O] water brain positron emission tomography imaging. In a subset of older adults (n=24; 70.0±2.0 years), aortic stiffness (carotid femoral pulse wave velocity) and cerebrovascular reserve (change in global CBF after intravenous infusion of acetazolamide) were assessed. In the entire cohort, global CBF was lower in older compared with young adults (36.5±1.1 versus 50.5±0.7 mL/min per 100 mL; P<0.001). Global CBF was higher in young women compared with young men (51.0±0.30 versus 47.4±0.03 mL/min per 100 mL; P<0.001) but did not differ between older women and men (P=0.63). In older adults, greater carotid femoral pulse wave velocity was associated with lower cerebrovascular reserve (r=−0.68; P=0.001 adjusted for age, sex, and mean arterial pressure) but not global CBF (r=0.13; P=0.60). Brachial pulse pressure was not associated with lower cerebrovascular reserve (r=−0.37; P=0.159) when adjusted for age and sex. These data indicate that the age-related increases in aortic stiffness may contribute, in part, to the brain's impaired ability to augment blood flow in response to a stimulus with aging in humans. (Hypertension. 2018;72:476-482.

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Section: Pet Imagingmentioning

confidence: 99%

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans

DuBose¹,

Ponto²,

Moser³

et al. 2018

Hypertension

View full text Add to dashboard Cite

show abstract

“…Nevertheless, advanced MRI techniques (e.g., diffusion tensor imaging [DTI], arterial spin labeling [ASL]) have been utilized for in-vivo quantification of neurotrauma-related brain changes in Veterans (see Wilde et al, 2015 for review). However, while some studies find robust brain differences in Veterans with history of TBI relative to those with no history of head trauma ( Mac Donald et al, 2011 , Miller et al, 2016 , Petrie et al, 2014 , Ponto et al, 2016 ), others fail to detect any alterations ( Jorge et al, 2012 , Levin et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

“…Reduced CBF has been demonstrated to not only precede, but also directly contribute to negative WM micro- and macro-structural changes in older adults ( Bernbaum et al, 2015 , Brickman et al, 2009 , Promjunyakul et al, 2015 , Promjunyakul et al, 2016 , ten Dam et al, 2007 ). Importantly, while both CBF and WM changes have been independently examined within TBI ( Delano-Wood et al, 2015 , Ponto et al, 2016 , Vas et al, 2016 ), few studies have explored relationships between CBF and WM within this population. This is especially critical given CBF reductions could serve to exacerbate or contribute to any trauma-induced WM alterations well beyond the time of initial injury.…”

Section: Introductionmentioning

confidence: 99%

Dynamic association between perfusion and white matter integrity across time since injury in Veterans with history of TBI

Clark

Bangen

Sorg

et al. 2017

NeuroImage: Clinical

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ObjectiveCerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Although both CBF and white matter microstructural alterations have been observed within the context of traumatic brain injury (TBI), the degree to which these pathological changes relate to one another and whether this association is altered by time since injury have not been examined. The current study therefore sought to clarify associations between resting CBF and white matter microstructure post-TBI.Methods37 veterans with history of mild or moderate TBI (mmTBI) underwent neuroimaging and completed health and psychiatric symptom questionnaires. Resting CBF was measured with multiphase pseudocontinuous arterial spin labeling (MPPCASL), and white matter microstructural integrity was measured with diffusion tensor imaging (DTI). The cingulate cortex and cingulum bundle were selected as a priori regions of interest for the ASL and DTI data, respectively, given the known vulnerability of these regions to TBI.ResultsRegression analyses controlling for age, sex, and posttraumatic stress disorder (PTSD) symptoms revealed a significant time since injury × resting CBF interaction for the left cingulum (p < 0.005). Decreased CBF was significantly associated with reduced cingulum fractional anisotropy (FA) in the chronic phase; however, no such association was observed for participants with less remote TBI.ConclusionsOur results showed that reduced CBF was associated with poorer white matter integrity in those who were further removed from their brain injury. Findings provide preliminary evidence of a possible dynamic association between CBF and white matter microstructure that warrants additional consideration within the context of the negative long-term clinical outcomes frequently observed in those with history of TBI. Additional cross-disciplinary studies integrating multiple imaging modalities (e.g., DTI, ASL) and refined neuropsychiatric assessment are needed to better understand the nature, temporal course, and dynamic association between brain changes and clinical outcomes post-injury.

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“…This notion, that mTBI is associated with a disrupted cerebrovascular system, also extends to blast-related mTBI. Recent work by Ponto et al 44 showed reduced global cerebral blood flow in blast-related mild and moderate TBI patients who were on average 3 years removed from their injury compared to veteran controls. In addition, residual cerebrovascular impairments have also been reported in pediatric mTBI, with reduced cerebral blood flow in bilateral frontotemporal regions 45 and bilateral thalami 46 in children who were 3-12 months removed from their injury compared to controls.…”

Section: Neuroimaging Evidence Of Cerebrovascular Dysfunction In Mtbimentioning

confidence: 99%

A Cerebrovascular Hypothesis of Neurodegeneration in mTBI

Sullivan

2019

Journal of Head Trauma Rehabilitation

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Mild traumatic brain injury (mTBI) is a major public health concern that has generated considerable scientific interest as a complex brain disorder that is associated with long-term neural consequences. This paper reviews the literature on cerebrovascular dysfunction in chronic mTBI with a focus on the long-term neural implications of such dysfunction. Evidence is presented from human neuroimaging studies to support cerebrovascular involvement in long-term mTBI pathology. Additionally, a pathway between mTBI and neurodegeneration via cerebrovascular dysfunction is explored. Future work focused on identifying the neurobiological mechanisms underlying the neural consequences of mTBI will be important to guide therapeutic interventions and long-term care for mTBI patients.

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Preliminary Investigation of Cerebral Blood Flow and Amyloid Burden in Veterans With and Without Combat-Related Traumatic Brain Injury

Cited by 18 publications

References 40 publications

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans

Dynamic association between perfusion and white matter integrity across time since injury in Veterans with history of TBI

A Cerebrovascular Hypothesis of Neurodegeneration in mTBI

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