William M Brooks

University of Kansas Medical Center · Hoglund Biomedical Imaging Center

Background: Cognitive reserve may protect against cognitive decline. Objective: This cross-sectional study investigated the association between cognitive reserve and physiological measures of cognitive workload in older adults with cognitive impairment. Methods: 29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MoCA: 20±7)...

T2‐Relaxation‐Under‐Spin‐Tagging (TRUST) is an MRI technique which allows for the measurement of brain blood oxygenation. Global venous oxygenation has been shown to decrease over the course of life and may prove useful as a measure of brain aging. No studies to date have examined the association between cardiovascular fitness and brain venous oxyg...

Background Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related...

The third positive peak of the event‐related potential (ERP P3) is understood to reflect neural resource utilization during working memory. We previously showed lower P3 ERP amplitude of the task effect in older adults with preclinical Alzheimer’s disease (AD). The aim of this study was to compare changes from baseline to 1‐year follow‐up in P3 ERP...

Background: Cognitive reserve may protect against cognitive decline. However, its effect on physiological measures of cognitive workload in adults with cognitive impairments is unclear. Objective: The aim was to determine the association between cognitive reserve and physiological measures of cognitive workload in older adults with and without cogn...

Embryonic palate development involves bilateral vertical growth of palatal shelves - extensions from the maxillary processes - next to the tongue until embryonic day (E) 13.5. Following vertical growth, palatal shelves elevate and adhere above the tongue by E14.5. Current models indicate that this process of elevation involves a complex vertical to...

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Cerebral edema following TBI is known to play a critical role in injury severity and prognosis. In the current study we used multimodal magnetic resonance imaging (MRI) to assess cerebral edema 24 hours after unilateral contusive TBI in male and female rats...

End-stage kidney disease has been associated with cognitive impairment and brain atrophy. It remains unclear if mild to moderate kidney dysfunction is associated with brain atrophy, especially in older adults. We used cross-sectional data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), an NIH-funded multicenter longitudinal cohort stud...

Emerging evidence from animal and human studies shows that beta‐amyloid (Aβ) may induce neuronal hyperexcitability in the early stage of Alzheimer’s disease (AD). Electroencephalography (EEG) offers unparalleled temporal resolution in tracing distinct neurophysiological processes even in preclinical AD. The aim of this pilot study was to determine...

The P3 event‐related potential (ERP) is typically reduced and delayed in patients with Alzheimer’s disease (AD). The hippocampus is a core regulator of the P3 ERP. The aim of this study was to investigate the relationship between hippocampal volume and P3 peak amplitude and latency in cognitively normal older adults with (Aβ+) and without elevated...

Background: Growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD). The aim of this study was to compare neuronal excitability between cognitively normal amyloid positive (CNAβ+) and those without elevated amyloid (CNAβ-) older adults. We hypothesized CNAβ+ participants would...

Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-r...

Cognitive workload is increasingly recognized as an important determinant of performance in cognitive tests and daily life activities. Cognitive workload is a measure of physical and mental effort allocation to a task, which can be determined through self-report or physiological measures. However, the reliability and validity of these measures have...

Cognitive workload (mental effort) is a measure of attention allocation to a task, which can be administered through self-report or physiological measures. Cognitive workload is increasingly recognized as an important determinant of performance in cognitive tests and daily life activities. However, the reliability and validity of these measures hav...

Event-related potentials (ERPs) offer unparalleled temporal resolution in tracing distinct electrophysiological processes related to normal and pathological cognitive aging. The stability of ERPs in older individuals with a vast range of cognitive ability has not been established. In this test-retest reliability study, 39 older individuals (age 74....

Background CKD is associated with abnormalities in cerebral blood flow, cerebral neurochemical concentrations, and white matter integrity. Each of these is associated with adverse clinical consequences in the non-CKD population, which may explain the high prevalence of dementia and stroke in ESKD. Because cognition improves after kidney transplanta...

Introduction: Brain bioenergetics are defective in Alzheimer's disease (AD). Preclinical studies find oxaloacetate (OAA) enhances bioenergetics, but human safety and target engagement data are lacking. Methods: We orally administered 500 or 1000 mg OAA, twice daily for 1 month, to AD participants (n = 15 each group) and monitored safety and tole...

Introduction Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst enlargement, leading to kidney failure. Sirtuin-1 is upregulated in ADPKD and accelerates disease progression by deacetylating p53. Niacinamide is a dietary supplement that inhibits sirtuins at high doses. Methods We conducted an open-label, sing...

Background: Chronic kidney disease (CKD) is associated with abnormalities in cerebral blood flow (CBF), cerebral neurochemical concentrations and white matter integrity, each of which are associated with adverse clinical consequences in the non-CKD population, and may explain the high prevalence of dementia and stroke in end stage kidney disease (E...

Despite higher rates of hospitalization and mortality following traumatic brain injury (TBI) in patients over 65 years old, older patients remain underrepresented in drug development studies. Worse outcomes in older individuals compared to younger adults could be attributed to exacerbated injury mechanisms including oxidative stress, inflammation,...

Background and objectives: Cognitive impairment is common in patients with kidney disease and can affect physicians' perception and/or patients' ability to complete the pretransplant evaluation. We examined whether cognitive impairment influences the likelihood for transplant listing and whether patients with cognitive impairment take longer to be...

There is growing recognition of the problem of male bias in neuroscience research, including in the field of traumatic brain injury (TBI) where fewer women than men are recruited to clinical trials and male rodents have predominantly been used as an experimental injury model. Despite TBI being a leading cause of mortality and disability worldwide,...

The present study sought to determine whether supplementation of long‐chain polyunsaturated fatty acids (LCPUFA) during the first year of life influenced brain function, structure, and metabolism at 9 years of age. Newborns were randomly assigned to consume formula containing either no LCPUFA (control) or formula with 0.64% of total fatty acids as...

Pressure application to the lumbar spine is an important assessment and treatment method of low back pain. However, few studies have characterized brain activation patterns in response to mechanical pressure. The objective of this study was to map brain activation associated with various levels of mechanical pressure to the lumbar spine in healthy...

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidant...

Background There is increasing interest in the role of physical exercise as a therapeutic strategy for individuals with Alzheimer’s disease (AD). We assessed the effect of 26 weeks (6 months) of a supervised aerobic exercise program on memory, executive function, functional ability and depression in early AD. Methods and findings This study was a...

Raw Cognitive Test Scores. (DOCX)

Estimated effect of the difference in baseline to week 26 change in the AEx group versus baseline to week 26 change in the ST group, adjusted for education. (DOCX)

Study protocol. (PDF)

CONSORT checklist. (PDF)

Estimated effect of the difference between groups at Week 26, adjusted for education. (DOCX)

Missing Test Scores Due to Unable-to-Complete. (DOCX)

Study design: Cross-sectional study. Objective: The aim of this study was to determine whether low back pain (subacute and chronic) is related to differences in brain volume. Summary of background data: Inconsistent findings have been reported about the effect of chronic low back pain on brain volume, and the effect of subacute low back pain o...

The guinea pig is a frequently used animal model for human pregnancy complications, such as oxygen deprivation or hypoxia, which result in altered brain development. To investigate the impact of in utero chronic hypoxia on brain development, pregnant guinea pigs underwent either normoxic or hypoxic conditions at about 70 % of 65-day term gestation....

Objective: To compare regional brain volume predictors of percent weight loss (WL) in dieters with obesity (DwO) and in the same participants categorized as "successful" (≥7% WL) or "unsuccessful" dieters (<7% WL). Methods: DwO (n = 72) and participants with healthy weight (n = 22) completed a structural MRI at baseline and 3 months. All DwO par...

Background: End-stage renal disease (ESRD) is a disease with an aging population and a high prevalence of cognitive impairment affecting quality of life, health care costs and mortality. Structural changes in the brain with decreased white matter integrity have been observed in ESRD. Understanding the changes in cognition and associated changes in...

Following a brain injury, the mobilization of reactive astrocytes is part of a complex neuroinflammatory response that may have both harmful and beneficial effects. There is also evidence that astrocytes progressively accumulate in the normal aging brain, increasing in both number and size. These astrocyte changes in normal brain aging may, in the...

Nephrogenic systemic fibrosis (NSF) is a devastating condition associated with gadolinium (Gd3(+)) based contrast agents (GBCAs) in patients with kidney disease. The release of toxic Gd3(+) from GBCAs likely plays a major role in NSF pathophysiology. The cause and etiology of Gd3(+) release from GBCAs is unknown. Increased Acidic Serine Aspartate R...

Objective Changes in food-cue neural reactivity associated with behavioral and surgical weight loss interventions have been reported. Resting functional connectivity represents tonic neural activity that may contribute to weight loss success. This study explores whether intervention type is associated with differences in functional connectivity aft...

To investigate the impact of chronic hypoxia on neonatal brains, and follow developmental alterations and adaptations noninvasively in a guinea pig model. Chronic hypoxemia is the prime cause of fetal brain injury and long-term sequelae such as neurodevelopmental compromise, seizures, and cerebral palsy. Thirty guinea pigs underwent either normoxic...

Background Smokers show increased brain activation in reward processing regions in response to smoking-related cues, yet few studies have examined secondary rewards not associated with smoking (i.e., money). Inconsistencies exist in the studies that do examine secondary rewards with some studies showing increased brain activation in reward processi...

Circulating adipokines are associated with physiological and pathophysiological processes in both obesity and pregnancy. Obesity in pregnancy increases the risk of pregnancy complications and the majority of research uses body mass index (BMI) to assess fatness. Specific fat compartments are associated with obesity-induced health risks yet it is no...

Although the advent of new food technologies has afforded the agricultural industry more expedient means of producing foods, the use of many of these technologies has stirred controversy among consumers. When deciding whether to purchase a food, consumers must now consider how they feel about the technology used to produce it. Despite this trend, o...

Brain bioenergetic function declines in some neurodegenerative diseases, this may influence other pathologies and administering bioenergetic intermediates could have therapeutic value. To test how one intermediate, oxaloacetate (OAA) affects brain bioenergetics, insulin signaling, inflammation and neurogenesis, we administered intraperitoneal OAA,...

Objective Obese children demonstrate less activation in prefrontal regions associated with self-control and inhibition when presented with food cues and advertisements. The current study evaluates the differences between obese and healthy weight children in resting-state functional connectivity to these brain regions. Design and Methods Seed regio...

Few studies have examined brain changes in response to effective weight loss; none have compared different methods of weight-loss intervention. We compared functional brain changes associated with a behavioral weight loss intervention to those associated with bariatric surgery. 15 obese participants were recruited prior to adjustable gastric bandin...

The decline in neuronal function during aging may result from increases in extracellular glutamate (Glu), Glu-induced neurotoxicity, and altered mitochondrial metabolism. To study metabolic responses to persistently high levels of Glu at synapses during aging, we used transgenic (Tg) mice that over-express the enzyme Glu dehydrogenase (GDH) in brai...

Abnormal task-related activation in primary motor cortices (M1) has been consistently found in functional imaging studies of subcortical stroke. Whether the abnormal activations are associated with neuronal alterations in the same or homologous area is not known. Our goal was to establish the relationships between M1 measures of motor-task-related...

Background and Objectives: Reaching is one of the arm major functions and has poor recovery after stroke. Although kinematic metrics of reaching reflect “true” impairment after stroke, these metrics are largely ignored in functional MRI studies. In this study, we examined the relationship between motor–related activation of the primary motor cortex...

Background: Magnetic resonance imaging (MRI) after deep brain stimulation (DBS) carries the risk of heating at the lead-contacts within the brain. Objective/hypothesis: To compare the effect of single- and dual-channel DBS implantable pulse generator (IPG) configurations on brain lead-contact heating during 3T MRI. Methods: A phantom with bila...

Background: Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies. Objective: We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand...

Objective: To evaluate brain activation in response to common food and nonfood logos in healthy weight and obese children. Study design: Ten healthy weight children (mean body mass index in the 50th percentile) and 10 obese children (mean body mass index in the 97.9th percentile) completed self-report measures of self-control. They then underwen...