Browsing by Subject "Cognitive Dysfunction"
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Item Assessment of Brain Perfusion and Vascular Compliance with Magnetic Resonance Imaging(2018-02-28) Li, Yang; Choi, Changho; Lu, Hanzhang; Vinogradov, Elena; Shang, Ty; Liu, HanliBrain perfusion is an index that reflects the amount of blood received by the brain tissue in a given time period. Normal brain perfusion ensures that sufficient oxygen, glucose, and other nutrients are delivered to the neurons and glial cells in the brain. While perfusion is relatively static index of brain vascular function, vascular compliance represents the dynamic ability of arteries to dilate or retract in response to blood pressure alternations. An artery vessel with high compliance can better buffer the pulsatility of blood flow, thereby protecting the downstream arterioles and capillaries from damage. Consequently, brain perfusion and vascular compliance are complementary properties of brain's vascular system and may be important indicators of cerebrovascular health. Therefore, noninvasive imaging of brain perfusion and vascular compliance will provide valuable biomarkers to study cerebral physiology and function. Furthermore, these biomarkers may also yield crucial pathophysiological knowledge and guide therapies in brain disorders, such as stroke, small-vessel disease, and neurodegenerative disease. This thesis consists of three novel tools toward brain perfusion and vascular compliance imaging. I first developed a cardiac-triggered Arterial-Spin-Labeling (ASL) technique to enhance the sensitivity of brain perfusion MRI without using exogenous contrast agent. I demonstrated its utility in several experimental settings, including single-shot acquisition, multi-shot acquisition, and detection of cerebral blood flow (CBF) changes. Next, I worked on the analysis strategies of perfusion MRI data. I developed a cloud-based tool for ASL data processing that is free from any software installation, compatible with file formats from all major MRI manufacturers, and publicly accessible. Quantitative CBF maps and region-specific reports are available for download within minutes. I have launched this cloud service recently and received initial feedback from researchers around the world. Finally, I developed a technique to measure vascular compliance in larger cerebral arteries. I used a time-resolved vascular-space-occupancy technique to obtain 3D maps of cerebral arterial compliance and then applied the technique to study arterial stiffness in aging.Item A Data-Driven Approach for Deriving Parkinson’s Disease Subtypes and Related Trajectories of Cognitive and Motor Function(2018-07-27) Dhima, Kaltra; Lacritz, Laura H.; Hynan, Linda S.; McClintock, Shawn Michael; Dewey, Richard B., Jr.; German, DwightParkinson's disease (PD) is a progressive neurological illness that involves a variety of motor and non-motor features, with remarkable heterogeneity in clinical presentation and symptom progression. Previous studies have attempted to identify PD subtypes to better understand the clinical implications of this heterogeneity, though reliable subtypes remain unclear due to inconsistencies across studies, non-generalizable samples, and low subtype stability over time. This study aimed to identify PD subtypes based on motor, cognitive, psychiatric, and functional measures using K-means cluster analysis in a large PD sample (N=683) and explore subtype-specific prognosis. Results yielded a two-cluster solution (Cluster 1 N=457; 2 N=226) at baseline with adequate cluster quality. Cluster 1 exhibited more severe rest tremor but better functioning in all other measures (independence with activities of daily living, daytime sleepiness, depression, anxiety, general non-motor PD symptoms, and postural instability/gait difficulty). Ten half-sample replications of the cluster analysis model and Cohen's kappa revealed excellent model consistency in symptom trends and subjects' cluster membership. Comparison of additional baseline measures using analysis of covariance (ANCOVAs) found that Cluster 1 performed better in overall disease burden, quality of life, motor symptoms, PD medication side effects, mood, sleep dysfunction, compulsive behaviors, psychomotor processing speed, attention, and Aβ-42. ANCOVAs for annualized change showed Cluster 2 exhibiting greater disease burden over time according to a composite measure, with insignificant cluster differences for all other longitudinal analyses. Replication of the cluster analysis model at last visit revealed consistent cluster differences among model measures, but with suboptimal stability over time, as over 25% of subjects changed cluster membership from baseline. The current study utilized a large and heterogeneous PD sample and a statistically advanced subtyping approach to derive a two-cluster solution, with one group exhibiting relatively greater severity of rest tremor but better functioning in all other areas used to determine initial group differences, as noted above. Although several significant and clinically manful cluster differences were observed at baseline, longitudinal analyses revealed limited clinical and prognostic usefulness. Future PD subtyping efforts may consider increased variable diversity, novel statistical clustering methodologies, and examining clusters of symptom trajectories rather than baseline symptoms.Item Identifying Predictors of Reversion from Mild Cognitive Impairment to Normal Cognition(2015-07-15) Pandya, Seema Yogendra; Woon, Fu Lye; Lacritz, Laura H.; Weiner, Myron F.; Deschner, Martin; Jeon-Slaughter, HaekyungStudies on mild cognitive impairment (MCI) have focused on identifying predictors of progression to dementia, yet relatively few studies have examined predictors of reversion from MCI to normal cognition. This retrospective study incorporated data from the National Alzheimer's Coordinating Center Uniform Data Set to examine baseline predictors of MCI reversion. A total of 1,208 participants meeting MCI criteria were evaluated at baseline visit and three subsequent annual visits. Of these, 175 (14%) reverted to normal cognition, 612 (51%) remained MCI, and 421 (35%) progressed to dementia at two-years, with sustained diagnoses at three-years. This study only examined MCI participants who reverted to normal cognition (175) and progressed to dementia (421) for a final total of 596 participants. Baseline predictors of MCI reversion were categorized into the clusters of demographic/genetic data, global functioning, neuropsychological functioning, medical health/dementia risk score, and neuropsychiatric symptoms. Binary stepwise logistic regression models were used to identify significant predictors of MCI reversion compared to MCI progression for each cluster, which were then entered into a final comprehensive model to find the overall significant predictor(s). Receiver operating characteristic (ROC) curves were then used to determine cut-off scores for the continuous predictors most significant for MCI reversion. The variables most significantly associated with MCI reversion were younger age, being unmarried, having zero copies of the APOE ε4 allele, lower Clinical Dementia Rating Sum of Boxes scores, and higher test scores on Logical Memory Delayed Recall, Vegetable Fluency, and Boston Naming Test at baseline. ROC curve results revealed a standard z-score of -1.16 or better on Logical Memory Delayed Recall as an accurate classification of the MCI reversion group from the MCI progression group, with 89% sensitivity and 73% specificity. Results suggest that demographic, global functioning, and neuropsychological factors are significantly associated with MCI reversion. Future longitudinal studies on MCI reversion, with a multifactorial approach, are necessary to increase understanding of MCI reversion. Findings could help educate patients and families on clinical outcomes of MCI, better inform healthcare providers on treatment management and clinical prognosis, and increase precision of findings in early intervention studies of dementia.Item Neuropsychological Functioning in Aging National Football League Retirees(2020-08-01T05:00:00.000Z) Schaffert, Jeffrey Michael; Cullum, C. Munro; Didehbani, Nyaz; LoBue, Christian; Motes, Michael A.; Hart, John, Jr.Concussive and sub-concussive head impacts sustained over a National Football League (NFL) career have been proposed to increase risk for later cognitive impairment. However, research is generally limited on the neuropsychological functioning among NFL retirees, and no studies to date have investigated the cognitive performance of NFL retirees over time. Study One was a critical review of research on neuropsychological functioning among NFL retirees. Findings were mixed, but studies suggested some NFL retirees have lower verbal memory, confrontation naming, and executive functioning abilities compared to control groups. Investigations of dose-response relationships between cognition and head-injury exposure also generated mixed findings which may be related to small samples, sampling bias, small effect sizes, and the measurement of different head-injury exposure variables. Study Two was a prospective cohort design investigating neuropsychological functioning and head-injury exposure in NFL retirees aged 50 and up. Retirees underwent baseline (N = 53) and follow-up (N = 29) comprehensive neuropsychological evaluations. Cognitively normal retirees (n = 26) were age, education, and IQ-matched to healthy controls (n = 26). Retirees diagnosed with MCI or dementia (n = 27) were matched as closely as possible to a clinical sample of patients with MCI and dementia by age, education, and diagnosis (n = 22). Independent samples t-tests and repeated measures ANCOVAs were used to evaluate neuropsychological scores between groups. Pearson correlations, partial correlations, and quadratic regressions were used to examine relationships between head-injury exposure and neuropsychological scores. Head-injury exposure variables included concussions, number of concussions with loss of consciousness, years playing professionally, games played, games started, and age beginning tackle football. Overall, NFL retirees did not significantly differ on the majority of measures at baseline or on any measures over time compared to their respective control groups. Furthermore, the vast majority of neuropsychological scores were not significantly related to head-injury exposure, regardless of cognitive diagnosis. In totality, findings suggest that NFL retirees do not have lower cognitive functioning compare to non-athlete controls later in life, and that head-injury exposure obtained over an NFL career is not related to cognitive functioning later-in-life.Item Neuropsychological Predictors of Time to Conversion from Mild Cognitive Impairment to Alzheimer's Disease(August 2021) Parker, Allison Nicol; Cullum, C. Munro; McClintock, Shawn Michael; Rossetti, Heidi; Hynan, Linda S.; Nguyen, TrungMild Cognitive Impairment (MCI) is a risk state for the development of Alzheimer's disease (AD), though individual outcomes vary. Accurately predicting which MCI patients are likely to develop AD and how long they have until the onset of dementia could provide both patients and their families sufficient time to prepare. Neuropsychological tests have the advantage of objectively quantifying cognitive impairments, and may be useful in predicting time to conversion. The present project aimed to 1) compile the available literature concerning neuropsychological predictors of conversion from MCI to AD using systematic review and meta-analytic techniques and 2) to determine if neuropsychological profiles differentiate MCI patients who convert to AD sooner, those who convert later, and those who do not convert utilizing a statistical technique known as profile analysis. Findings from the systematic review illuminated several gaps in the literature such as the small number of studies that follow patients over longer periods of time. Results from the meta-analysis suggested that word recall and recognition tasks, complex figure recall tasks, simple shape recall tasks, Trail Making Task B (TMT-B), semantic fluency, and the Mini Mental State Examination (MMSE) differentiated between MCI patients who convert sooner (within three years) from those who maintain an MCI diagnosis over three years. Results from the second part of the project found that verbal memory measures best distinguished those who converted sooner from those who converter later. In comparison with those who convert within three years, the group that maintained an MCI diagnosis completed TMT-B more quickly and performed better on memory measures. Neuropsychological measures did not distinguish between those who maintained an MCI diagnosis and those who converted after three years. Taken together, results from the two studies suggest that clinicians may wish to rely upon memory measures and TMT-B performance when considering recommendations regarding length of follow-up and planning for the onset of dementia in patients with MCI. In order to better understand predictors of time to conversion from MCI to AD, future studies should follow participants over several years and make direct comparisons between those who convert sooner and those who convert later.Item Predictors of Persistent Neurobehavioral Symptoms in Adolescents with Mild Traumatic Brain Injury Using a Novel Clinical Tool(2021-07-23) Wright, Brittany Nicole; Brewer-Mixon, Karen; Cullum, C. Munro; Juengst, Shannon B.; Krumwiede, Kimberly Hoggatt; Terhorst, Lauren; Wilmoth, Kristin MichellePersistent post-concussion symptoms in adolescents are non-specific and poorly understood. A small percentage of adolescents (roughly 20%) will experience persistent symptoms following mTBI that can be disruptive in many areas of daily functioning. Including measures in assessment that are specific to adolescents but capture symptoms beyond injury may lead to more insight as to why some adolescents experience persistent symptoms. Moreover, identifying predictors of persistent symptoms could aid in management and evaluation of symptoms. The current set of studies was designed to validate a measurement tool for adolescents and identify predictors of persistent symptoms in a cohort of adolescents with mTBI. Study 1 was designed to further validate a tool (the BAST-A), which assesses persistent emotional and behavioral symptoms in adolescents. Another aim was to develop ordinal to continuous normed scores to aid in clinical interpretation. When assessing the psychometric indicators of the tool, both the Negative Affect and Fatigue and Executive and Social Function subscales performed well. However, the Risk Behaviors subscale performed poorly in this sample of adolescents with sports-related concussion. Specifically, Risk Behaviors was not able to distinguish different severity levels in the sample. Results from this study suggest further psychometric validation of the BAST-A in adolescents with mTBI. The aim of Study 2 was to utilize the ordinal to continuous normed scores in the first study to assess if a combination of predictors was associated with persistent neurobehavioral symptoms in adolescents with mTBI. A combination of pre-injury and injury predictors was significantly associated with self-reported Negative Affect and Fatigue symptoms (F (8,93) =6.09, p<.001) and Executive and Social Function symptoms (F (8,93) = 2.18, p=.036). Due to limitations within the Risk Behaviors subscale, binary (Yes/No) outcomes were used. A combination of pre-injury and injury factors was also significantly associated with self-reported Risk Behaviors [χ2(8) = 18.84, p=.016]. Across subscales, total number of recent life stressors remained a significant predictor of persistent symptoms. The results from this study indicated that a combination of injury-related and personal factors is predictive of persistent symptoms and that recent life stressors contribute to the experience of these symptoms.Item Self-Reported Head Injury: Associated Risk in Mild Cognitive Impairment and Progression to Alzheimer Disease(2016-07-27) LoBue, Christian Barrett; Cullum, C. Munro; Woon, Fu Lye; Rossetti, Heidi; Hart, John, Jr.; Hynan, Linda S.Traumatic brain injury (TBI) has been associated with a higher risk for and earlier onset of neurodegenerative disorders, including Alzheimer disease (AD), but its mechanistic link is not well understood. TBI has been hypothesized to activate a progressive neurodegenerative process, accelerate an already present neurodegenerative disorder, or disrupt neuronal/cognitive reserve and interact with aging. Although previous research has investigated the link between TBI and dementia, little is known if TBI is also associated with development of mild cognitive impairment (MCI), a prodromal phase of AD, and progression from MCI to AD. This broad investigation consists of two studies devised to examine whether a history of TBI is a risk factor for MCI and progression from MCI to AD using a large, multicenter national database. The aim of Study 1 was to determine if a history of TBI with LOC was associated with an increased risk for and earlier onset of MCI. Results revealed that a history of TBI was associated with a 1.35 fold higher risk for a diagnosis of MCI, even after adjusting for well-known factors linked to cognitive decline. A history of TBI was also linked to a nearly 2 year earlier age of MCI diagnosis. Thus, a TBI history does appear to be associated with an earlier diagnosis of MCI and may be a risk factor for MCI. Study 2 was devised to investigate whether a history of TBI with LOC was associated with progression from MCI to AD. Results revealed that individuals with a history of TBI with LOC did not show faster progression from MCI to AD, higher annual rates of progression, or more rapid cognitive decline than those without a TBI history, suggesting that a history of TBI was not linked to progression from MCI to AD. This two-part investigation indicates that a history of TBI appears to be a risk factor for earlier development of MCI; however, once the neurodegenerative process for MCI to AD starts, a history of TBI appears unrelated to subsequent decline.Item [UT Southwestern Medical Center News](2010-02-10) Ladson, LaKisha