Catherine Elizabeth Price, PhD - US grants

21+ years old; Adult; Age; Aged 65 and Over; Ammon Horn; Arthroplasty, Replacement, Knee; Biochemical Markers; Brain; CRISP; Cardiac; Cardiac Surgery; Cardiac Surgery procedures; Cardiac Surgical Procedures; Cognitive; Cognitive Disturbance; Cognitive Impairment; Cognitive decline; Cognitive function abnormal; Collaborations; Communities; Computer Retrieval of Information on Scientific Projects Database; Cornu Ammonis; Country; Development; Disturbance in cognition; Elderly; Elderly, over 65; Encephalon; Encephalons; Florida; Funding; Georgia; Georgia (Republic); Georgia SSR; Georgia, USA; Georgia, Western Asia; Georgian S.S.R.; Georgian SSR; Grant; HOSP; Hippocampus; Hippocampus (Brain); Hospitals; Human, Adult; Impaired cognition; Individual; Institutes; Institution; Investigation; Investigators; Knee Replacement, Total; Knee arthroplasty; Knee joint replacement operation; Knee replacement; Life Expectancy; MR Imaging; MR Tomography; MRI; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Markers, Biochemical; Measurement; Measures; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; NIH; NMR Imaging; NMR Tomography; National Institutes of Health; National Institutes of Health (U.S.); Nervous System, Brain; Neurocognitive; Nuclear Magnetic Resonance Imaging; Numbers; Operation; Operative Procedures; Operative Surgical Procedures; Orthopedic; Orthopedic Surgery procedures; Orthopedic Surgical Profession; Orthopedics; Participant; Post-Operative; Postoperative; Postoperative Period; Procedures; Prosthetic total arthroplasty of the knee; Protocol; Protocols documentation; QOL; Quality of life; Research; Research Personnel; Research Resources; Researchers; Resources; Risk; Source; Surgery, Orthopedic; Surgical; Surgical Interventions; Surgical Procedure; Surgical Procedures, Heart; TKR - Total knee replacement; Testing; Total Arthroplasty of the Knee; USA Georgia; United States Department of Veterans Affairs; United States National Institutes of Health; United States Veterans Administration; Universities; Veterans Administration; Veterans Administration (U.S.); Veterans Affairs (U.S.); Week; Western Asia Georgia; Zeugmatography; adult human (21+); advanced age; cognitive dysfunction; cognitive loss; cognitively impaired; elders; experience; geriatric; heart surgery; hippocampal; late life; later life; older adult; older person; senior citizen; surgery

DESCRIPTION (provided by applicant): Parkinson's disease (PD) affects more than 1.5 million people in the United States alone;its prevalence increases with age, and the majority of the diagnoses occur over age 60. While PD is primarily associated with motor symptoms such as resting tremor and rigidity, it is also associated with debilitating cognitive symptoms. The uniqueness of this application is the candidate's focus on the role of white matter integrity on cognitive function in PD. Little is known about white matter and cognition in PD despite growing research suggesting pathological changes in the white matter may contribute to the degenerative disease. The career development plan consists of two core training objectives: 1) specialty training on the cognitive-behavioral patterns and theories of PD, 2) focused training on Diffusion Tensor Imaging (DTI) methods. Supplementary training in biostatistics, research ethics and grant writing is included. The candidate's long-term career goals are to apply these skills towards longitudinal investigations examining the predictive value of white versus gray matter on cognitive decline (dementia) in PD and cognitive outcome following PD specific medical interventions (i.e., deep brain stimulation). These research interests are strongly supported by the candidate's primary college, The University of Florida's College of Public Health and Health Professions, as well as the College of Medicine where she has an adjunct appointment. The candidate will carry out her research with the co-mentorship of Professors Dawn Bowers, Ph.D. (Neuropsychology, UF), Thomas Mareci, Ph.D. (Biochemistry and Molecular Biology, UF), Glen Stebbins, Ph.D. (Department of Neurological Sciences, Rush University), and an advisory panel of Professors in the Departments of Neurology, Neuroscience and Biostatistics. The research will determine 1) the contribution of white matter integrity on the processing speed and working memory deficits of idiopathic PD (n=45) relative to that of an age and education matched control group (n=45), and 2) the predictive role of white matter on cognitive change after one year. Methods include a baseline MRI and cognitive assessment with a repeat cognitive assessment in one year. Relevance to Public Health: This project will contribute much needed knowledge about the role of white matter integrity on cognitive function in PD. The information will contribute to our ability to predict cognitive change in PD thereby improving treatment decisions and intervention options for PD.

DESCRIPTION (provided by applicant): Older adults are at increased risk for cognitive decline following major surgeries with this having implications for neurodegenerative acceleration as well as post-operative and long-term care costs. Orthopedic replacement surgeries such as total knee replacement surgery have the highest rates of cognitive decline in older adults. This is alarming, for older adults are increasingly seeking joint replacement to reduce associated osteoarthritis pain and increase activity (i.e., quality of life). Unfortunately at present there ae no specific surgical or anesthetic mechanisms for post-operative cognitive dysfunction. Results from our NIA funded pilot training grant, however, show preliminary evidence demonstrating that patients' pre-surgical brain integrity is an important indicator for post-operative outcome. We now seek to acquire definitive evidence for these markers using a larger sample size and also explore the interaction between pre-operative neuronal integrity and specific perioperative variables (e.g., anesthesia depth, emboli number). Aim 1 is to examine the integrity of the white matter regions connecting the frontal to subcortical structures and the hypothesis that patients with less deep white matter integrity will be vulnerable to post-operative executive decline. We further hypothesize that this disruption is driven by compromise to an important white matter circuit connecting the dorsolateral prefrontal cortex to the caudate (subaim 1). Aim 2 is to examine the integrity of the medial temporal structures to support the hypothesis that patients' with reduced pre-surgical hippocampal-entorhinal connectivity are vulnerable to post-operative memory decline. In Aim 3, we explore which peri-operative variables (e.g., intraoperative emboli, embolic stroke, anesthesia duration) interact negatively with baseline neuroimaging variables. These aims will be carried out by a multidisciplinary team with expertise in neuropsychology, geriatrics, dementia, post-operative cognitive dysfunction, anesthesiology, and orthopedic surgery. We will conduct a prospective longitudinal study with two groups: older adults (age > 60 years) having total knee replacement (n=80) and non-surgery age and education matched peers with osteoarthritis (n=80). Both groups will acquire baseline MRI using sophisticated diffusion and functional measures to define specific neuronal regions of interest, and complete cognitive testing at a pre-surgery/baseline time point followed by repeat testing at three weeks, three-months, and one-year post-operative/post-baseline. Participants will also acquire a repeat MRI 48 hours after their baseline scan to identify changes in brain structure (i.e., embolic stroke). Overall, the study's findings will bring us closer to understanding neural mechanisms for post- operative cognitive dysfunction, will help argue for basic pre-operative MRI screening for certain older adults, and assist us in the development of intra-operative interventions for patients with neuronal vulnerabilities.

DESCRIPTION (provided by applicant): Parkinson's Disease (PD) affects at least 1.5 million people in the United States alone. One of the most severe non-motor symptoms of PD is cognitive dysfunction involving reduced processing speed/working memory, and/or episodic memory. Relative to other neurodegenerative disorders with cognitive impairment, we know little about the neuroanatomical correlates of cognitive decline in PD. In preliminary work, we have examined brain connectivity associated with cognition in a group of idiopathic non-dementia PD relative to non- PD age-matched peers. Three distinct cognitive phenotypes were observed: a) slow information processing speed with preserved episodic memory, b) episodic memory difficulty with subtle slow information processing speed; and c) normal functioning with no deficits relative to age matched peers. Preliminary results of high angular resolution diffusion imaging suggest unique white matter and gray matter profiles: PD with episodic memory deficits exhibited mesial temporal circuit disruption (i.e., entorhinal-hippocampal connectivity); PD with primary processing speed deficits displayed aberration in the frontal-subcortical white matter circuitry (DLPFcircuit) between the dorsolateral prefrontal cortex and caudate; and PD without cognitive deficits showed circuitry similar to age-matched controls. The present study will recruit from one of the largest movement disorder databases in the country to investigate working hypotheses regarding memory and processing speed/executive difficulties and regional white matter connectivity within the temporal and frontal-subcortical regions, respectively. Three specific aims will be addressed. Aim 1: to demonstrate the association between memory function and the connectivity between the entorhinal cortex and hippocampus; Aim 2: to examine the relation between reduced processing speed/working memory and integrity within the DLPF cortex to caudate; and Aim 3: to reveal the significance of regional brain connectivity on memory or executive function decline at one and two years post-baseline. A research team specialized in movement disorders, functional and diffusion imaging, neuropsychological assessment, reliable change analyses, and longitudinal statistical modeling will carry out these aims. Study methods will draw from unique PD patient database, state-of-the art imaging techniques, and resources from the General Clinical Research Center within the Clinical and Translational Science Institute.

Cognitive disorders are a key health problem affecting millions of individuals, a problem that is increasing in importance as America's population ages. Just a single dementia, Alzheimer's disease, is estimated to afflict some 5.4 million Americans in 2012, projected to rise to 11-16 million by 2050, with the potential for staggering cost both in dollars and human costs for the afflicted and their caregivers. Yet cognitive health is not monitored effectively in the way that physical conditions and wellness are: physician visits routinely include screens for heart disease, diabetes, etc., but there is far less consistent screening for cognitive status. This project seeks to develop rapid, precise, and objective cognitive assessment tools that will provide operationally defined, quantitative metrics with sufficient sensitivity and specificity to aid in early detection and diagnosis of neurodegenerative disorders, as well as monitoring disease process and treatment efficacy. Its evidence-based approach offers the possibility of earlier treatment, which can slow the progress of cognitive disease, resulting in better quality of life.

The first research objective is to develop two new digital versions of two traditional tests. The digital Maze Completion (dMC) assesses frontal brain system associated cognitive functions by providing measures of tiered decision making and executive planning, and calibration of memory function by measuring the effect of priming. The digital Symbol-Digit Test (dSDT) assesses executive function by measuring information processing speed, and calibrates planning and cognitive shifting by detecting and measuring subtle behaviors. Both tests provide new measures of learning, assessing reaction time changes and short term memory retention. The second objective is to develop the algorithms required to detect subtle behaviors during the dMC and dSDT tests, which can serve as a platform to which additional tests can easily be added. The third objective is to make all the tests as self-scoring as possible, through advances in signal interpretation. The fourth objective involves administering the dCDT, dMC and dSDT to both healthy adults and subjects with known cognitive impairments, permitting the calibration of the power and value of the tests. The final objective is to establish the validity of selected measures provided by the tests, by comparing the measures to standard cognitive test results, to specific neuroanatomical structures, and to external and subcortical gray matter integrity relative to white matter integrity. These research activities are integrated with education through projects in courses, engagement of graduate and undergraduate students in the research, and annual workshops for students.

ABSTRACT Preoperative cognitive impairment is common among older adults preparing for surgery. Despite growing evidence that preoperative cognitive/neuronal integrity is a risk factor for perioperative insults and post- operative adverse outcomes, health care systems do not systematically pre-operatively screen for cognition. Clinical researchers have yet to identify a pragmatic approach to pre-operative cognitive screening. Our team members have developed the digital Clock Drawing Test (dCDT), a tool that captures subtle behavioral variables during a rapid (5-minute) clock drawing assessment. The data and benefit afforded by this tool have yet to be considered across perioperative contexts. We will apply the dCDT within a large number of pre- surgical patients (n=5,000 per year) coupled with novel machine learning algorithms to address three specific aims. Aim 1: examine range and distribution of preoperative neurocognitive impairment with older adult preoperative patients relative to non-surgical older adult demographically matched peers (available n=2,400 via NIH/Boston University Framingham Heart Study) using novel previously unobserved dCDT graphomotor and decision making variables; Aim 2: examine the predictive validity of presurgical dCDT variables on postoperative, clinician reported/hospital recorded events; Aim 3: examine pre to postoperative 6-week, 3- month, and 1-year change in dCDT and NIH PROMIS metrics for thoracic (n=70), orthopedic (n=70), major abdominal-pelvic patients (n=70), and non-surgery peers (n=70). For the observational studies (Aim 1 and 2), individuals > 65 years presenting to the UFHealth presurgical clinic will complete the dCDT as well as a three- word memory test and frailty assessment as part of the standard clinical evaluation. Surgical and anesthetic details will be acquired via the electronic medical record. Clinically-relevant outcomes will include complications, length of stay, cost of care, functional capacity, and mortality. Outcomes will be supplemented by a separate longitudinally-studied subgroup (Aim 3) completing NIH PROMIS metrics at 6 weeks, 3 months, and 1year after surgery. Analyses will focus on stratifying distributions and clusters of dCDT characteristics across numerous sociodemographic, surgical, and anesthetic factors. The predictive value of the dCDT will be modeled relative to clinical outcomes. Changes in dCDT and baseline NIH PROMIS domains will be compared pre- and post-operatively and examined for interactions with longitudinal perioperative events. Subaims: We will apply `deep learning' approaches to drawings to identify novel features of pre-surgical patients relative to a large sample of demographically equated dCDT data points available through the Framingham Heart Study. Symbolic aggregate approximation (SAX)-based machine learning approaches will characterize interactions between preoperative dCDT features and intraoperative anesthetic sensitivities.

ABSTRACT Preoperative cognitive impairment is common among older adults preparing for surgery. Despite growing evidence that preoperative cognitive/neuronal integrity is a risk factor for perioperative insults and post- operative adverse outcomes, health care systems do not systematically pre-operatively screen for cognition. Clinical researchers have yet to identify a pragmatic approach to pre-operative cognitive screening. Our team members have developed the digital Clock Drawing Test (dCDT), a tool that captures subtle behavioral variables during a rapid (5-minute) clock drawing assessment. The data and benefit afforded by this tool have yet to be considered across perioperative contexts. We will apply the dCDT within a large number of pre- surgical patients (n=5,000 per year) coupled with novel machine learning algorithms to address three specific aims. Aim 1: examine range and distribution of preoperative neurocognitive impairment with older adult preoperative patients relative to non-surgical older adult demographically matched peers (available n=2,400 via NIH/Boston University Framingham Heart Study) using novel previously unobserved dCDT graphomotor and decision making variables; Aim 2: examine the predictive validity of presurgical dCDT variables on postoperative, clinician reported/hospital recorded events; Aim 3: examine pre to postoperative 6-week, 3- month, and 1-year change in dCDT and NIH PROMIS metrics for thoracic (n=70), orthopedic (n=70), major abdominal-pelvic patients (n=70), and non-surgery peers (n=70). For the observational studies (Aim 1 and 2), individuals > 65 years presenting to the UFHealth presurgical clinic will complete the dCDT as well as a three- word memory test and frailty assessment as part of the standard clinical evaluation. Surgical and anesthetic details will be acquired via the electronic medical record. Clinically-relevant outcomes will include complications, length of stay, cost of care, functional capacity, and mortality. Outcomes will be supplemented by a separate longitudinally-studied subgroup (Aim 3) completing NIH PROMIS metrics at 6 weeks, 3 months, and 1year after surgery. Analyses will focus on stratifying distributions and clusters of dCDT characteristics across numerous sociodemographic, surgical, and anesthetic factors. The predictive value of the dCDT will be modeled relative to clinical outcomes. Changes in dCDT and baseline NIH PROMIS domains will be compared pre- and post-operatively and examined for interactions with longitudinal perioperative events. Subaims: We will apply `deep learning' approaches to drawings to identify novel features of pre-surgical patients relative to a large sample of demographically equated dCDT data points available through the Framingham Heart Study. Symbolic aggregate approximation (SAX)-based machine learning approaches will characterize interactions between preoperative dCDT features and intraoperative anesthetic sensitivities.

ABSTRACT Our healthcare system faces larger numbers of individuals with early to late Alzheimer?s Disease (AD) and other neurodegenerative disorders requiring anesthesia associated procedures for serious health related conditions (e.g., cardiac), screening (e.g., colonoscopy), or quality of life improvement (e.g., joint replacement). Despite evidence that preoperative cognitive status is a risk factor for negative post-operative outcomes, there is a scarcity of research addressing perioperative cognitive-biomarker-anesthesia interactions, and evidence based anesthesia-surgical practices for patients with prodromal or diagnosed dementias. The K07 applicant- an NIH funded independent investigator and board certified neuropsychologist with expertise in the cognitive sequelae and associated neuroimaging markers of AD, vascular dementia, and other neurodegenerative disorders, and cognitive and neuroimaging predictors of perioperative cognitive complications and delirium. The applicant (with support of the institution) is proposing a Perioperative Cognitive Anesthesia Network (PeCAN) Program for AD and related dementia. The purpose? to promote institutional and community awareness of cognition and memory in older adults electing surgical procedures with anesthesia, intensify collaborations on AD biomarkers- anesthesia interactions, and promote translation of research findings to clinical care. The applicant will complete advanced leadership training and three programmatic aims. Aim 1- convene a multidisciplinary advisory team to establish four integrated PeCAN research cores targeting AD and related dementia perioperative research. Cores include a Cognitive-Clinical Core, a Neuroimaging Core, a Biomarker Core, and a Data Science Core. Aim 2- enhance defined and supportive pathways to the PeCAN cores so that early stage investigators can efficiently initiate and complete perioperative-neurodegenerative research. The applicant will integrate pathways between multiple institutional resources including NIH funded 1Florida Alzheimer?s Disease Research Center, Evelyn F. McKnight Brain Institute, the University of Florida (UF) Institute on Aging Pepper Center, and the UF Fixel Center for Neurological Diseases. Aim 3- promote the emergence of highly trained scientists and educators for innovative team science addressing perioperative neuronal risk and mechanisms for protection. Methods will involve implementation of a certificate program, interdisciplinary team-science research opportunities, and pilot funding supported through this grant and institutional matching funds. Trainees will initially include appropriate predoctoral T32 trainees, neuropsychology fellows, and anesthesiology fellows. Milestones- annual analyses of programmatic strengths/weaknesses, multidisciplinary proposal submissions, and evidence of trainee success with perioperative research for AD and related dementias.