Aging / Alzheimer's

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    Comparison of support vector machine, random forest, extreme gradient boosting and lasso and elastic-net regularized generalized linear model for Alzheimer's Disease prediction
    (2021) Zhang, Fan; Petersen, Melissa; Johnson, Leigh; Hall, James; O'Bryant, Sid
    Purpose: Machine learning based blood test shows promise in detecting Alzheimer's disease (AD) and pinpointing mechanisms underlying the process of neurodegeneration. Model selection plays a crucial role in building good machine learning models for AD prediction. Methods: The paper presents a comparison of four machine learning algorithms: support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost )and lasso and elastic-net regularized generalized linear model (GLMNET) for Alzheimer's disease prediction using blood test data from serum. First, we implemented 10 times repeated 5-fold cross-validation to split the data into training set and testing set randomly 50 times to select the best hyperparameters for each selected machine learning method. Then we selected the best learning model based on the performance metrics in the testing set. Results: Of all compared prediction results in the training set, RF and XGBoost achieved the highest negative predictive value (100%) followed by SVM with 99.40% and GLMNET with 94.45%. Of all compared prediction results in the testing set, SVM achieved the highest negative predictive value (96.96%) followed by XGBoost with 95.94%, RF with 95.59%, and GLMNET with 94.27%. With 28-cores high performance computing, RF took 1.35 hours CPU usage, SVM 1.10 hours, XGBoost 48 seconds, and GLMNET 47 seconds, respectively. Conclusions: SVM, RF, and XGBoost are the top three best models for AD prediction. SVM performs better in handling overfitting problem in the training set with small size than RF and XGBoost and also achieved best performance in the testing set.
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    Improving Fall Risk Assessments in Elderly Rural Populations
    (2021) Johnson, Jordyn; Gold, Vanna; Gibson, John; Hadley, Lesca
    Purpose This QI project was implemented to improve the screening for fall risks in patients over 65 who were not already using a walking assistive device. The town of Lampasas has a population of 19.4% over the age of 65 and there is currently little being done to identify fall risks. Methods Fall risks were identified using the "Get Up and Go" test in which patients were asked to go from a seated position to standing, walk across the room, and return to their chair. The administrator of the test was to watch for any difficulty standing, unsteadiness, or difficulty walking. Ideally, if a fall risk was identified, the administrator should then discuss preventative measures. Results Data collection was done on two separate days. The first day recorded how many screenings were done without intentional implementation of the project. Zero fall risk assessments were done during that day. The second was running the project and including the Get Up and Go test as part of the physical exam. Of the nine possible patients who could have been screened, seven were for an overall increase of 75%. Conclusions A key lesson learned was planning screenings in a way that is practical and easy. The get up and go test is easy to include in physical exams and provides a sampling of a patients mobility. The next steps would be to include the screening as part of the physical exam template in order to que providers to do the assessment.
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    Self-Management Program for Brain Health
    (2021) Jose, Roslin; Kannan, Srijaa; Ross, Sarah; Quiceno, Mary; Severance, Jennifer
    Purpose: While developing dementia may be unavoidable, various factors contribute to its onset including lifestyle choices. The purpose of this study is to implement a program supporting lifestyle changes to improve brain health and cognitive functioning with hopes of preventing or delaying dementia. Methods: Health coaching, education and targeted assessments with feedback will be used to provide a personalized approach to addressing brain health. Inclusion criteria: ≥ 18 years old without dementia or uncontrolled psychiatric illness. Participants can choose to receive health coaching through a digital tool or in-person. They will complete assessments for each of the pillars of Brain Health: Diet, Exercise, Social Engagement, Cognitive Activity, Sleep, Mindfulness & Outlook, and General Health. Demographics, motivation to change and cognitive status will also be assessed. Health coaching will last 3 months with assessments for the pillars given 3 months before starting, at the start, at the end, and 3 months after completion. We will evaluate scores for each assessment at various points in time for improvement or other trends. Results: This program is in the beginning stages of implementation. Conclusion: This self-management program intends to promote lifestyle changes that will reduce the risk of developing dementia. If individuals make improvements in the seven pillars, they can expect optimization of cognitive functioning and risk reduction for developing dementia. Clinical implications include the development of an evidence-based program for addressing risk factors for dementia with potential for preventing or delaying its onset.
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    Effects of Animal Assisted Intervention for Individuals with Dementia
    (2021) Hollingshead, Kaitlyn; Bustos, Annika; Salem, Yasser; Liu, Howe
    Purpose: The purpose of this systematic review was to examine the evidence regarding the effectiveness of AAI for individuals with dementia. Methods: Two authors reviewed relevant literature and compiled a list of articles that were then sorted based on the predefined inclusion and exclusion criteria. Studies were included if they met the criteria of adult patients with a diagnosis of any type of dementia and included AAI with dogs. Articles were excluded if they were not available in English, included the use of robots or stuffed animals, or utilized other types of animals for the intervention. Study characteristics, such as the amount and duration of interventions, and specific methodological criteria, were related to reported effects. Results: The initial search resulted in retrieval of 306 articles. These articles were further reviewed to ensure that the methods coincided with established inclusion criteria and resulted in 20 articles. A variety of animal assisted activities were used with a focus on improving quality of life, mood, behavior, cognitive state, and functional activities. Various outcome measures were used to measure the effects of AAI including those that were specific to patients with dementia, and other non-specific measures to assess quality of life, mood, behavior, cognition and functional activities. Conclusion: The evidence suggests that AAI may have a positive effect on quality of life, agitation and depression, social interaction and physical activity in individuals with dementia. There was significant variability between studies regarding prescription of intervention, sample size and outcome measures used to document change.
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    Characterization of Mitochondrial DNA Damage in Complex Disease Using Two Different NGS Platforms
    (2021) Reid, Danielle; Phillips, Nicole; Barber, Robert C.; Blessing, Alexandra M.
    Purpose: The Hispanic/Latinx aging (65+) population is expected to increase through 2060 causing the number of Alzheimer's Disease (AD) cases in the Hispanic/Latinx population to quadruple. Several risk factors for developing cognitive impairment are prevalent among Mexican Americans (MAs), although the etiology of these associations remains unclear. Age-associated decline in mitochondrial function results in accumulation of reactive oxygen species (ROS) capable of damaging essential biomolecules, including DNA. The mitochondrial genome is particularly vulnerable to DNA damage, which has a strong correlation with AD pathology. Developing an improved method to assess mitochondrial oxidative damage may help resolve the potential association between abnormal mitochondrial function as indicated by oxidative DNA damage in cognitively impaired MAs. Oxidative damage to guanine (G) forming 8oxoG, is one of the most prevalent DNA lesions. Current methods for detection are limited and lack reproducibility. Lifestyle and/or metabolic health may contribute directly to age-related neurodegeneration. Methods: We aim to investigate the mutational load indicative of oxidative DNA damage in MAs compared to non-Hispanic white (NHW) participants in a human AD cohort, TARCC, who were diagnosed with AD, type-2 diabetes (T2D), and comorbidity (AD/T2D) using Illumina-based NGS. Additionally, we propose nanopore sequencing technology as an improved alternative to current detection/quantification methods. Results: We describe preliminary proof-of-concept results and future applications of this method to analyze mtDNA damage in participants of TARCC. Conclusion: Investigation of oxidative DNA damage may aid our understanding of the differences in manifestation of age-related dementia in MAs.
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    Advance Care Planning
    (2021) Ross, Sarah; Vu, Katie; Ahmed, Maheen
    Advance care planning (ACP) is the process of communicating with patients and their families about the type of healthcare the patient wishes to receive. The Merit-based Incentive Payment System (MIPS) has ACP as a measure, communicating to providers the value of having ACP discussions with older adults. ACP provides an opportunity for patients to communicate what is most important to them for end-of-life healthcare. Each HSC Health provider is a Merit-based Incentive Payment System (MIPS) eligible clinician. The MIPS measure for ACP is assessed over a calendar year (from January 1st to December 31st). In September 2019, an online learning module educating providers on the basics of Advance Care Planning was made available for the HSC Clinical Practice Group. In this research project, we evaluate the effect of the online ACP module on primary care providers (Family Medicine and Geriatrics) performing and documenting advance care planning. Data from January 1, 2019 to December 31, 2020 was extracted, and descriptive statistics used to compare overall performance rates between 2019 and 2020. Results indicate that from 2019 to 2020 providers in Geriatrics and Family Medicine collectively improved in documenting that ACP was reviewed. Providing education on the importance of ACP and how to perform an ACP visit is one of the interventions that has promoted improvement in the overall practice performance on the MIPS measure of ACP from 2019 to 2020.
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    (2021) Abdali, Kulsum; Chen, Xiaoan; Cai, Ming; Ross, Sarah; Davis, Sandra; Zhou, Zhengyang; Shi, Xiangrong
    Purpose: Aging affects the cardiovascular function. This study tested the hypothesis that aging diminishes cerebral perfusion during hypotension challenge. Methods: Healthy elderly (n=13) and young (n=13) adults signed a consent form that was approved by IRB at UNTHSC. Heart rate (HR), mean arterial pressure (MAP), and cerebral blood flow velocity of the middle cerebral artery (VMCA) were continuously measured during systemic hypotension, which was induced by rapid-deflation of bilateral thigh-cuffs after 3-min supra-systolic occlusion. This hypotension elicited a transient-decrease in VMCA (ΔVMCA) and a reflexive-increase in HR (ΔHR). Time duration reaching the nadir of MAP and VMCA (T0) and the rate of the recovery response (TR) were compared between the groups. Results: Cuff deflation after occlusion to the legs significantly decreased MAP (ΔMAP) which elicited significant hypoperfusion to the brain in both groups. Although ΔMAP and ΔVMCA were not statistically different between the groups, both T0 and TR for MAP and VMCA were significantly longer in the elderly group. T0 and TR were shorter for ΔVMCA than ΔMAP, suggesting the presence of cerebral autoregulation, which evoked an early recovery of ΔVMCA from its nadir, and also explained an early completion of VMCA recovery before MAP restoration. In addition, the rates of ΔMAP and ΔHR during recovery were diminished with aging, which explained a prolonged recovery of cerebral perfusion. Conclusion: We conclude that aging diminishes the function of maintaining cerebral perfusion during hypotension, which is associated with age-impaired cerebral intrinsic factor and systemic function.
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    CMS MIPS Quality Measures Are Blind to High-Need High-Cost Homebound Older Adults Cared for in Home-Based Medical Care
    (2021) Bhatnagar, Shivani
    Purpose: Multiple studies find home-based medical care a solution for high-need, high-cost homebound older adults. However, home-based medical care needs proper representation among the Merit-based Incentive Payment System (MIPS) and Center for Medicare and Medicaid Services (CMS)-specified quality measures to be financially viable in modern value-based care. Unfortunately, many useful measures for this population are unusable due to inadequate home medical visit codes in these measures' denominators. The objective of this study is to determine what proportion of the CMS 2019 MIPS Quality Measures that are potentially appropriate for patients receiving home-based medical care have home visit codes in their denominators. Methods: All 257 CMS 2019 MIPS Quality Measures were reviewed for applicability to homebound older adults cared for by home-based medical care providers. Measure details were reviewed in public documents from five CMS websites across 2017-2019. Results: Of the 257 CMS 2019 MIPS Quality Measures, 179 were inapplicable for this population, most commonly because they applied to specialist physicians outside of geriatric or palliative providers. Of the 78 measures that were deemed potentially appropriate, only 37 (47%) had home visit codes. Conclusions: The majority of CMS MIPS Quality Measures that are potentially appropriate for the care of homebound older adults, who receive home-based medical care, are unusable by home-based medical care practitioners for MIPS reporting. This represents a barrier for home-based medical providers in delivering effective care to this high-need, high-cost vulnerable patient population.
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    The Effect of COVID19 on the Caregivers of Dementia Patients
    (2021) Whittaker, Eric; Oderberg, Jane
    Purpose Investigating the effects of COVID19 on caregivers of dementia patients is paramount because of challenges such as limited resources, separation from patient, and neglect of personal health. By evaluating these effects on caregivers we can improve pandemic response to improve healthcare outcomes. This inquiry focused on describing the impact of COVID on caregivers of patients with dementia using survey data. Methods Inclusion criteria selected for caregivers of dementia patients from the UNTHSC Dementia CARES Program in 2019 (Quality Improvement Project). 17 caregivers responded to a survey during summer 2020. Participants rated how often they experienced situations due to COVID changes on a scale of "never" to "nearly always." Responses were analyzed using Qualtrics. Results Results indicate 18% of caregivers felt overwhelmed during COVID. Nearly 25% reported mental health concerns and an equal proportion felt their life would be less challenging without restrictions. Most participants never faced unique financial challenges and reported the availability of services was adequate. 35% reported difficulty attending to personal health needs because of COVID related changes to their caregiving role. Conclusions The results suggest a need to address mental health, personal health, and unique challenges from the pandemic. Financial burden was less of a challenge, however conclusions are limited due to sample size. This investigation is relevant because to treat dementia patients holistically, physicians must address the health of those who influence outcomes. By increasing data and awareness we can improve outcomes for caregiver and patient during future pandemics through quality patient care and policy.
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    Incorporating Medical Students into the Development of Age Friendly Healthcare Systems through Quality Improvement Projects
    (2021) Murphy, Joshua; Philip, Timothy; Severance, Jennifer; Gibson, John; Hadley, Lesca
    Purpose: The world is aging. Health systems are often not prepared for the number or complexity of geriatric patients. Caring for this vulnerable population through age-friendly health systems is imperative for our future. With the universal lack of geriatricians, family physicians primarily care for the elderly population and are therefore ideally placed to lead changes to improve the lives of geriatric patients. The Rural Osteopathic Medical Education (ROME) Program partnered with UNTHSC's Center for Geriatrics to create geriatric-focused quality improvement projects (QIPs) for medical students to complete in their family medicine clerkships. Methods: ROME students surveyed rural family physicians regarding geriatric needs in their patient population. The results were analyzed to determine patient clinical needs as well as physician educational needs. Geriatric QIPs were developed from the survey results and implemented into the clinics. Results: 100% of the students stated that they are better able to analyze, collect, and communicate data about quality improvements in practice. 100% of the students stated that they would integrate QIPs into their practices. 67% of the family physicians strongly agreed that QIPs were useful to their practice. Conclusions: Students identified best practices to address the health needs and concerns of older adults and their caregivers. The QIPs improved care for the elderly in addition to providing experience in implementing quality improvement methods that can be used in the students' future medical practices. Incorporating medical students into QIPs in family medicine clinics is valuable for the patients, students, and physicians.
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    The Role of Lipid Rafts on Androgen's Neurotoxic Effects
    (2021) Fadeyibi, Oluwadarasimi; Rybalchenko, Nataliya; Cunningham, Rebecca
    Purpose: Vascular dementia (VaD) is a form of cognitive decline resulting from cerebrovascular disease in blood vessels. VaD is an age-related disease accounting for approximately 17-25% of cases of dementia, with men having a higher risk. Oxidative stress (OS) plays a large role in aging associated diseases, such as VaD. Using an in vitro model, our prior studies show androgens, the major male sex hormone, through an androgen receptor (AR) localized to lipid rafts in the plasma membrane exacerbates OS, which may worsen VaD. We seek to determine if interfering with AR localization to cholesterol-rich lipid rafts decreases androgen induced neurotoxicity. Methods: Since testosterone is only toxic under OS conditions, we exposed N27 cells to H2O2 (20 uM) to induce an OS condition followed by testosterone (100 nM). Nystatin (50 uM) was used to decrease cholesterol-rich lipid rafts that contain AR in order to block testosterone's damaging effects in an OS environment. The MTT assay was used to quantify cell viability. AR and lipid raft proteins were quantified. Results: Cholesterol inhibition using nystatin decreased both AR and lipid raft proteins. Nystatin blocked testosterone exacerbation of H2O2 induced cell loss. Conclusion: This study shows that the loss of lipid rafts via nystatin blocked androgen-induced OS in cells by altering the structure and function of AR. During VaD, neuronal dysfunction can impair cognition, thus this study suggests that repurposing statins for the treatment of VaD may be useful.
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    Efficacy of the Geriatric Depression Scale-30 and 15 for Elderly Patients in a Primary Care Setting
    (2021) Banh, Debini; Davis, Sandra
    The Geriatric Depression Scale (GDS) was developed to be used as a screening tool specifically for the geriatric population and categorizes patients into no depression, mild depression, moderate depression, and severe depression based on their total scores (Yesavage, 1982). The original GDS-30 (30 survey items) was shortened to GDS-15 (15 survey items) in hopes of maintaining the efficacy in a shorter administration time. The prevalence of geriatric depression is estimated to be about 15-20% of patients (Mitchell). Unfortunately, many of the elderly also believe that they do not need help managing their depression, and thus do not seek help from their primary care physicians (Brenes). Properly screening all patients for depression with a shortened GDS may reduce the number of depression cases missed during the yearly health exams compared to purely relying on patients' reports of their symptoms. The data were collected from the one hundred forty-two patients' first visit over a 12 month period from June 2019 to June 2020. We concluded that the GDS-15 is an easier way to screen all geriatric patients for depression while patients wait to begin the clinic visit with their physician. Further studies will focus on the treatment plan for the mild, moderate, and severe depression as defined by the GDS-30 and GDS-15.
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    The Effects of Methamphetamine on Oxidative Stress Markers in the Brain
    (2021) Davis, Delaney; Vann, Philip; Wong, Jessica; Metzger, Daniel; Shetty, Ritu; Forster, Michael; Sumien, Nathalie
    In the last decade, prescription stimulants have gained popularity in young adults despite the potential adverse consequences. Amphetamine-like compounds, even at moderate doses, promote the production of reactive oxygen species via dopamine-dependent pathways. We hypothesized that late neurobehavioral deficits were caused by heightened oxidative stress as a response to early chronic exposure to methamphetamine. Four-month-old male and female mice were injected with either saline or methamphetamine twice a day for 4 weeks. After behavioral testing at 9-10 months of age, the mice were euthanized and brain regions were dissected (cortex, cerebellum, hippocampus, striatum, midbrain). These regions were used to measure markers of oxidative stress and dopaminergic function. Preliminary outcomes revealed that dopaminergic function was not majorly affected by methamphetamine treatment, whereas lipid peroxidation levels were increased in the cerebellum of males and in the cortex and midbrain of females. These preliminary results suggest that early chronic methamphetamine administration induced changes in oxidative stress, and more so in the females than the males. These data indicate possible long-term consequences on functional and biochemical changes that will be examined in future studies.
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    Role of DNA Methylation in Risk for Alzheimer's Disease and Type 2 Diabetes in a Mexican American Cohort
    (2021) Barber, Robert C.; Abraham Daniel, Ann; Hall, Courtney; Sun, Jie; Phillips, Nicole; Silzer, Talisa
    PURPOSE: Age related diseases such as Alzheimer's disease (AD) and type 2 diabetes (T2D) are respectively the 6th and 7th leading cause of mortality in the US. Mexican Americans, the largest ethnic minority group in the US, have an increased likelihood of developing T2D compared to their Caucasian counterparts. With the elderly Mexican American population (≥65 years old) likely to multiply 7-fold by 2050, prevalence of AD alongside T2D is predicted to increase too. Mexican Americans have an earlier onset of AD and a metabolic heavy predisposition for AD compared to Caucasians who develop inflammation-based AD. The risk for T2D and AD is multifactorial involving epigenetic factors such as methylation, which is the addition of a methyl group to the cytosine base of DNA. We aim to establish an epigenetic association between AD and T2D unique to the Mexican American population. METHODS: Participants from the Texas Alzheimer's Research and Care Consortium (TARCC), which consists of Mexican American individuals diagnosed with either AD only, T2D only or AD and T2D matched with a Caucasian counterpart were selected. Peripheral blood was drawn from participants and individual methylation profiles collected using the Illumina Infinium MethylationEPIC chip array. Differential methylation will be assessed using the Chip Analysis Methylation Pipeline (ChAMP) package in R. RESULTS: Results obtained will be analyzed using pathway and gene set enrichment analysis tools. CONCLUSIONS: Identifying possible methylation sites associated with T2D and AD unique to the Mexican American population could contribute towards developing ethnicity-specific biomarkers and treatments.
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    Assessing Benzodiazepine Use in the Elderly
    (2021) Wickramage, Pavithra; Gibson, John; Hadley, Lesca
    Chronic benzodiazepines are frequently prescribed to patients above the age of 65 for anxiety and/or insomnia. They are listed in the Beer's criteria as medication that should not be prescribed to the geriatric population. In order to understand prescribing habits and limit the use of benzodiazepines in this demographic, a protocol following the Patient Monitoring Program (PMP) Narx Score was studied. Patients about the age of 65 who have a sedative score about 200 according to their PMP report were identified and recommended for tapering of medication and/or referral to psychiatry. Willingness to taper off medication was considered a positive result and compared to data gathered before this enhancement. After the implementation of the above-mentioned enhancement, 100% of patients were willing to be tapered off medication. This is in contrast to the 67% that were willing to be tapered off before. Significance for the terms of this study was set to be if greater than 50% of patients were willing, which was a success rate present before and after the enhancement. In conclusion, the utilization of the sedative NARX proved to be an effective method to identify patients who are at great risk of chronic benzodiazepine use. The age of the patient is used to calculate said score. Although the use of this score was beneficial to improving patient outcomes in the studied clinic, future studies should be implemented in clinics who did not have a prior history of geriatric patient education already implemented into the clinic culture.
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    Glial cell line-derived neurotrophic factor and Parkinson's disease: Is its family receptor the missing link?
    (2021) Kasanga, Ella; McElroy, Christopher; Shifflet, Marla; Salvatore, Michael
    Purpose: Glial cell line-derived neurotrophic factor (GDNF) improved motor function in Parkinson's disease (PD) preclinical and Phase I trials whereas mixed results were generated for Phase II trials. This disparity in outcome may be attributed to several factors including disease severity at treatment onset. Although GDNF is delivered to the striatum, increasing reports suggest that its recovery in the substantia nigra (SN) is vital for motor recovery, a process which may be compromised with PD progression. GDNF delivery in aged rats, wherein bradykinesia is evident, induces expression of its family receptor, GFR-ɑ1, in the SN. Indeed, replenishment of GFR-ɑ1, which is decreased in the SN in aged models, improves motor function, suggesting that GFR-ɑ1 may be critical for motor benefits. Using a hemi-Parkinson's model wherein bradykinesia is also evident, we evaluated for changes in GFR-ɑ1 expression with lesion progression. Method: 3-month old male Sprague-Dawley rats were euthanized on days 7 and 28 post-lesion induction for neurochemical assays. Results: A lesion-associated decline in GFR-ɑ1 protein expression was observed in the striatum at both time points. Also, there was a more significant reduction in the 28-day versus 7-day cohort denoting a progressive loss of GFR-ɑ1. Conclusion: These results suggest that GFR-ɑ1 in the striatum declines with nigrostriatal dysfunction progression and thus, may be a limiting factor in GDNF efficacy. Maintaining GFR-ɑ1 expression in the striatum may therefore be a link in the restorative capacity of GDNF.