Aging / Alzheimer's

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    Does polypharmacy education increase patient desire to reduce amount of prescription medications taken daily?
    (2022) Patchen, Hope; Furman, Erik
    Purpose: Increased awareness of polypharmacy and its inherent risks in the medical community has made the management of medications in the elderly an important aspect of primary care.1,2 Although the benefits of deprescribing are well understood, providers still encounter barriers to deprescribing including patient hesitance or fear of discontinuing medications.2,3 This project was designed to increase patient understanding of polypharmacy and its inherent risks, and to determine whether increased understanding affected the patient's desire to reduce the amount of prescription medications taken daily. The project was designed with the hope that patients would be more aware of the medications they use and more amenable to deprescribing interventions in the future. Methods: Patients presenting to an outpatient family practice clinic were administered an optional survey that gathered information regarding their personal medication use. This survey included an educational component designed to inform patients of polypharmacy and its inherent risks. Participants responses were recorded, given numeric values according to their level of understanding, and excluded if a participant's response was indeterminable. Participants' understanding of polypharmacy and its associated risks, as well as their desire to reduce daily prescriptions, was analyzed before and after completing the included educational material using a paired sample t-test in Microsoft Excel. Results: 30 patients agreed to complete the survey over a span of three weeks, 86 % of which were 65 or older. Although 80 % of patients surveyed were experiencing polypharmacy by its traditional definition, over 85 % of patients surveyed had never heard of polypharmacy or had low understanding of the term. The statistics showed a significant increase in the understanding of the term polypharmacy as well as its associated risks in participants, but no significant increase in the number of participants who desired to decrease the amount of prescriptions they take daily. 70 % of patients indicated that they planned to bring a list of their medications to their next appointment. Conclusions: This study suggests that many patients, even those experiencing polypharmacy, are not aware of its risks. Although educating patients about polypharmacy and its associated risks did increase understanding, it did not significantly change patients' desires to reduce the amount of prescriptions taken daily. More than 50 percent of patients surveyed were already interested in reducing the amount of prescription medications they take daily prior to being educated about polypharmacy, possibly explaining the lack of significant change. Although overall understanding of polypharmacy did increase for this population, there were individuals who still rated their understanding as "low". Gathering participant feedback regarding the educational material may offer insight into what was and was not effective. Additionally, increasing the sample size and engaging a more diverse population may provide greater insight to patient understanding and desires.
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    Association between inflammation, white matter hyperintensities, and executive function: the role of ethnicity.
    (2022) Brown, Frank; Vintimilla, Raul; Hall, James; Johnson, Leigh; O'Bryant, Sid
    Association between inflammation, white matter hyperintensities, and executive function: the role of ethnicity. Frank Brown1, Raul Vintimilla2, James Hall2, Leigh Johnson2, Sid O'Bryant2, for the HABS-HD Study Team. 1University of North Texas 2University of North Texas Health Science Center, Institute for Translational Research Background: Systemic inflammation and cardiovascular risk factors (CVRF) impact neurological health and executive function. Neutrophils produce inflammatory mediators and lymphocytes regulate the inflammatory response. Neutrophil to lymphocyte ratio (NLR) has been used as a marker of systemic inflammation, and as a predictor of cardiovascular health. CVRF are correlated with white matter hyperintensity volume (WMH), an MRI indicator of cerebrovascular health. This study seeks to compare if there is a difference in the association between inflammation (NLR), WMH, and executive function among Mexican Americans and non-Hispanic Whites. Method: We analyzed data from 1083 (505 Mexican Americans and 578 non -Hispanic Whites) cognitively normal participants from the Health and Aging Brain Study (HABS-HD). All participants signed a written consent, and underwent a 3T MRI (Siemens Skyra), clinical labs, clinical evaluation, and cognitive testing. Differential blood cell counts were used to obtain NLR. WMH volume was measured from FLAIR using the Statistical Parametric Mapping (SPM) Lesion Segmentation Tool. Linear regression was used to predict the effect of NLR and Log transformed WMH adjusted for intracranial volume (derived from Freesurferv6.0 analysis of T1 MPRAGE) on Trails B z-score (executive function), and to evaluate if NLR can predict WMH volume. Analysis was split by ethnicity. Age, sex, and education were entered as covariates in the models. Results: Sixty-four percent of the total sample were female. Means for the whole sample were: age 66.02, education years 12.98, Trails B 0.19, WMH volume -0.035, and NLR 2.16. When compared to non-Hispanic Whites, Mexican Americans were significantly younger, less educated, had lower Trails B score, NLR values and WMH volume. NLR predicted Trails B scores (B = -0.14, t =-0.12, p = 0.004) only in Mexican American, while WMH predicted Trails B scores in Mexican American (B = -0.16, t = -3.02, p = 0.003), and Non-Hispanic Whites (B = -0.14, t = -4.33, p < 0.0001). Results remained significant after adjusting for age, sex, education. NLR predicted WMH volume (B = 0.13, t = 3.38, p = 0.001) only in Mexican American. Conclusion: Our findings suggest an association between NLR, WMH and executive function in Mexican Americans. NLR and WMH volume predicted Trails B scores in Mexican Americans. WMH predicted Trails B scores, but there was no association between NLR and executive function in non-Hispanic Whites. These findings demonstrate the importance of race consideration when assessing the relationship between inflammation, CVRF, WMH, and executive function.
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    Subjective memory complaints and cardiovascular risk factors: a cross-sectional study of the HABS-HD cohort
    (2022) Mathew, Ezek; Vintimilla, Raul; Hall, James; Johnson, Leigh; O'Bryant, Sid
    Background: Subjective memory complaints (SMC) are considered as subjects' interpretation of their cognitive aspects, such as memory and perception. Cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and obesity may contribute to cognitive decline and their relationship with dementia has been documented extensively. However, there is a lack of literature on the relationship between CVRFs and SMC. Depression has been linked to cardiovascular disease and it is strongly associated with SMC, so it is important to consider the contribution of CVRFs and depression as potentially modifiable factors of SMC. Despite the importance of SMC as a risk factor for cognitive decline, and the higher burden of CVRFs, cognitive decline and dementia among minorities like Mexican Americans (MA), not much attention has been paid to the study of SMC in this population. This study examined the factors associated with SMC in community-dwelling older MA and non - Hispanic Whites (NHW), particularly CVRFs and depression. We hypothesized that CVRFs will be associated with SMC, and that the association will be independent of depression. Methods: We studied 1,376 cognitively normal participants (673 MA and 673 NHW) from the Health and Aging Brain Study (HABS - HD). Baseline characteristics were analyzed using t and chi square tests. The presence of SMC was ascertained by the Subjective Memory Complaints Questionnaire (SCMQ). A logistic regression was conducted to examine the relationship of subjective memory complaints with CVRFs and depression. Age, gender, and education were entered as covariates in the model. Results: MA with SMC had a higher prevalence of dyslipidemia (p=0.008), and depression (p< 0.0001) than those without SMC. Fifty nine percent of the NHW sample were female. NHW with SMC were less educated than those without SMC (mean education years 15.26 vs 15.83), and have a higher prevalence of diabetes (p=0.04) and depression (p< 0.0001). When comparing baseline characteristics of MA (323) and NHW (269) with SMC, we found that MA were younger (mean age 63.74 vs 68.85) and less educated (mean education years 9.38 vs 15.26). MA with SMC had a higher prevalence of diabetes (p< 0.0001) and obesity (p=0.0001) when compared with NHW with SMC. Depression was strongly associated with SMC in MA (OR 3.46; 95% CI = 2.45 - 4.89) and NHW (OR 2.22; 95% CI = 1.59 - 3.10). Dyslipidemia was also associated with SMC in MA (OR 1.73; 95% CI = 1.25 - 2.40). NHW with less education had an increased likelihood of exhibiting SMC. Conclusions: Our findings suggest that the association of CVRF and SMC differs among MA and NHW. Depression was strongly associated with SMC in both groups. In MA, dyslipidemia was also associated with SMC in MA, while education was a significant factor only in NHW. The complex relationship between memory complains, vascular risk factors, and depression requires longitudinal studies for further clarification. Understanding SMC and its racial differences may allow early interventions to prevent cognitive decline.
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    Effects on Stroop performance pre-and post-participation in the self management brain health coaching program
    (2022) Kannan, Srijaa; Ross, Sarah; Quiceno, Mary; Severance, Jennifer; Jose, Roslin; Clark, Emily
    Purpose: About ¼ of adults age 65 and older develop cognitive impairment without dementia. Of those who live past 85, 1/3 will develop some form of dementia. Currently, there is no cure for dementia. While developing dementia may eventually be unavoidable, various factors contribute to the onset of dementia including lifestyle choices. Modifiable risk factors related to lifestyle can be addressed through health coaching. The purpose of this study is to implement a program that supports participants in making lifestyle changes that will help them function optimally now, and promote brain health and cognitive functioning in the future to help reduce their risk of developing dementia. Methods: This is a longitudinal study design in which participants are measured multiple times throughout their participation. Health coaching, education, and targeted assessments with feedback are used to provide a personalized approach to addressing brain health. Program participants received in-person health coaching across a 3-month period. Study participants must be ≥18 years of age, with no dementia or uncontrolled psychiatric illness. Participants complete survey assessments for each of the seven pillars of Brain Health: Diet, Exercise, Social Engagement, Cognitive Activity, Sleep, Mindfulness & Outlook, and General Health. Additional information collected includes demographic information and assessments of cognition. The Stroop test is a cognitive assessment that measures attention, executive functioning, and processing speed. The Stroop test was performed prior to the start and upon completion of the program; pre and post participation results were evaluated for correlations. Results: Of the 36 participants who enrolled and completed the pre-surveys for the program, 25 progressed to participate in health coaching visits with personalized brain health lifestyle goals. The average age of participants is 76. 80% of the participants are female and 94% are Caucasian. The majority of participants chose improving cognitive activity as their area of focus. Feedback from those who completed the program has been positive. Participants stated that the program length met their need for implementing change, they would recommend the program to others, and they had positive experiences with the health coach. All participants who have completed the program to date have shown an improvement in the Stroop Test raw scores for words and colors comparing the initial intake visit to the closure visit. 50% of participants showed some improvement in the color-word raw scores. Conclusion: Participants in the self-management program for brain health show improvements in attention, executive functioning, and processing speed as measured by their performance on the Stroop test. As individuals make improvements in the seven pillars of brain health, they can expect optimization of cognitive functioning and risk reduction for developing dementia. The program allows individuals to focus on the areas of most importance to them, which contributes to their success. Recommendations for future studies includes tracking participants longitudinally with an aim to assess program benefit in preventing and delaying the onset of dementia.
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    Types of Telehealth services preferred by geriatric patients during the COVID-19 pandemic
    (2022) Nguyen, Matthew; Escobar, Krystal Cruz; Knebl, Janice; Garfield, Tyson
    Technologies' growing involvement in health care has led to continuous improvement in access, efficiency and quality of care, but specific challenges lie with addressing the barriers that impair the geriatric population from benefitting the use of new technology.1 The purpose of this quality improvement initiative was to obtain feedback from older adults and their caregivers regarding the usage of telehealth services during routine clinic care and their preferences for each type of visit. A convenience sample survey was administered to 55 geriatric patients older than 50 years old between June - October 2021 who have their medical at the University of North Texas Health Science Center - Center of Older Adults' ambulatory clinic. The survey included questions about the patients' demographics, the survey taker's relationship to the patient if not the patient, and their experiences with telehealth services. Additionally, the survey included questions using a Likert scale where the patient or caregiver ranked types of clinical visits they would prefer telehealth services for versus an in person clinic visit. Responses from the participants were compared based on the types of visits. Of the 55 respondents to the survey questionnaire, 37 were females and 18 were males and 45 were the older adult patients, 9 were family member caregivers and 1 non-family caregiver. The results indicated that the majority of patients and caregivers preferred the following types of visits as a telehealth visit: reviewing prescriptions, review of laboratory results, blood pressure management, and questions/screening about COVID-19. All other types of clinic visits, such as routine clinic visits for chronic conditions, acute illness symptoms, acute or chronic pain conditions, psychosocial needs and advanced care planning were preferred to be done in person. When asking about their experiences with telehealth services, geriatric patients used the telephone the most often for their medical needs. These findings indicate that geriatric patients prefer to continue traditional in person clinic visits for their acute and chronic disease management but are open to having discussions about their laboratory values, blood pressure management, reviewing medications and Covid-19 screening through telehealth. The high telephone telehealth usage suggests that the majority of geriatric patients are not comfortable and familiar with other forms of telehealth that includes the use of virtual platforms that has developed over recent years. Although telehealth cannot be used as a means to replace in person visits, it has been shown to have a place in clinical care for geriatric patients and their caregivers depending on the clinical needs.
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    Hyperbaric Oxygen Treatment improved Cognitive deficits in a mouse model of Alzheimer's Disease
    (2022) Mensah-Kane, Paapa; Vann, Philip; Davis, Delaney; Dory, Lad; Sumien, Nathalie
    Purpose: Alzheimer's disease (AD) is an economic burden affecting 40 million people worldwide and projected to increase to 120 million by the year 2050. Current approved treatments of AD only manage symptoms, involving anti-cholinesterase or NMDA antagonist. Seeking out new therapeutics and interventions that can reverse and alleviate the devastating effects of this disease has become paramount. Though a complex disease, there are major factors such as hypoxia, oxidative stress, and neuroinflammation that have been heavily involved in the pathogenesis of AD. Interventions that can reduce these two factors would likely reverse the progression of the disease. Hyperbaric Oxygen Therapy (HBOT), which has been used for the past 50 years for thermal burns, decompression sickness among other conditions, seems promising for neurological conditions such as traumatic brain injury and stroke. It has been shown to reduce inflammation and hypoxia. At the center of AD controversy also, is the relative vulnerability of the different sexes to AD. Whereas most studies in the US show no difference in incidence, studies in Europe have demonstrated a higher risk in women than men. On the contrary another study in United Kingdom reported men are at a higher risk. Thus, it has become more important to use both sexes in any study that seeks a successful treatment. Therefore, our aim was to explore whether HBOT can improve cognition in both male and female 5xFAD (AD model) mice. Methods: A total of 132 male and female 5xFAD and wildtype (WT) mice were randomly assigned to one of four experimental groups consisting of WT-HBOT, WT+HBOT, 5xFAD-HBOT and 5xFAD+HBOT. HBOT (O2 pressure at 2.4 ATA maintained for 90 min) daily (5 days/week) was started at 9-10 months and continued until the mice were euthanized at 12-13 months. Morris water maze test for spatial learning and memory, active avoidance T maze test for cognitive flexibility and fear conditioning test for associative learning were carried out at 1 month into the treatment with HBOT. Results: HBOT improved spatial learning and memory deficits in 5xFAD males but not in females. However, cognitive flexibility impairments were reversed with HBOT in 5xFAD females but not males. Also, HBOT improved associative learning in 5xFAD females, a deficit which was absent in males. Conclusion: This work does support HBOT as a viable option for reversing cognitive impairment associated with an AD phenotype with some sex differences depending on cognitive domain. Future work will seek to evaluate the mechanisms of action of HBOT including the possible involvement of epigenetics and sex differences, to help bring some clarity to the equivocal vulnerability of males and females to AD.
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    Older Adult Perceptions of Technology in Medicine
    (2022) Escobar, Krystal Cruz; Nguyen, Matthew
    Purpose: Technologies' growing involvement in health care has led to continuous improvement in efficiency and quality of care, but specific challenges lie with addressing the barriers that impair the geriatric population from benefitting the use of new technology. The purpose of this quality improvement initiative was to obtain feedback from older adults and their caregivers regarding a new electronic check in process in a geriatric primary care clinic. Methods: A cross sectional survey was administered to 70 older adults aged 65 and older between May - October 2021. Outcomes of interest included Internet access, device access, as well as user confidence with technology, and ability to effectively utilize new technologies. Results: Findings indicated 40% of the primary population were unable to complete the electronic check-in themselves; defaulting to assistance from their caregivers; who reported ease in completing the check in process. An average of 68% of participants reported an interest in learning more about technology from their health care provider. Our results indicate that although the geriatric population faced some hardship in navigating the online check in system, they are willing to adopt and learn about new technology. Conclusion: These findings provide a basis for how physicians can meet patient expectations and provide a future avenue of patient education to improve quality care to the geriatric population.
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    Differential associations between AV-45 brain amyloid and blood biomarkers by consensus diagnosis among adults with Down Syndrome
    (2022) Goehring, Leah; Petersen, Melissa
    Authors: Leah Goehring, Melissa Petersen, Michael Phelan, Lisa Taylor, Anne Fagan, Rachel Henson, Beau Ances, Nicole Schupf, Michael Yassa, Sharon Krinsky-McHale, Mark Mapstone, Florence Lai, H. Diana Rosas, Margaret Pulsifer, Christie Hom, Wayne Silverman, Ira Lott & David Keator Introduction: Individuals with Down Syndrome (DS) are at an increased risk for developing dementia, specifically Alzheimer's Disease (AD) due to triplication of Chromosome 21 leading to the overproduction of the beta amyloid. Few studies to date have examined the link between plasma biomarkers of AD pathology and brain amyloid in adults with DS who also have dementia. The aim of this study is to examine the relationship between specific plasma biomarkers (neurofilament light chain [NfL], total tau) and amyloid deposition in the brain among adults with DS. Methods: Data were analyzed on n=66 adults with DS (n=41 cognitively stable [CS]; n=16 mild cognitive impairment [MCI-DS]; n=9 dementia [DEM]) enrolled in the Alzheimer's Disease in Down Syndrome (ADDS) Study. Plasma concentrations of NfL and total tau were analyzed using Single Molecule Array (Simoa) technology.18F-AV-45 PET and T1-weighted MRI scans were collected to examine amyloid deposition in the brain. MRI-derived voxel-weighted SUVR averages were derived for each region of interest (ROI). A priori selected brain regions included the anterior/posterior cingulate, superior/inferior/middle temporal, superior frontal, inferior parietal, lateral occipital, orbitofrontal, lateral/medial orbitofrontal, and rostral middle frontal lobes. Fixed effect linear models were conducted with each diagnostic group to examine the association between the predictor variables (plasma biomarkers) with each of the a prior-identified ROIs, adjusting for linear effects of the covariates (age, ApoEe4, site, sex and brain volume). Results: Among those with DS who were determined to be CS, elevations in NfL were significantly associated with increased amyloid uptake in the superior temporal lobe, anterior cingulate, superior frontal lobe, inferior parietal lobe, inferior temporal lobe, orbitofrontal lobe, middle temporal lobe, lateral orbitofrontal lobe, medial orbitofrontal lobe and rostral middle frontal lobe. The latter ROI was also found to be significantly related to increased NfL levels among those with MCI-DS. No significant associations were found between NfL and amyloid deposition among any of the ROI examined for those with DEM. When examining the link between total tau and amyloid, the only finding was for those with a diagnosis of DEM, with a decrease in total tau found to be significantly associated with increased amyloid in the superior temporal lobe. Total tau was otherwise not found to be significantly related to amyloid deposition in any of the ROI for those with a diagnosis of CS or MCI. Discussion: Plasma biomarkers remain an appealing tool as they are less expensive and invasive as compared to other neuro-diagnostic modalities. Our study suggests that plasma biomarkers may be useful in tracking amyloid deposition in specific regions of the brain for adults with DS and highlight the potential utility for their application.
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    Effects of Diabetes and White Matter Hyperintensities on Cognition in Mexican Americans Based on APOE e4 Carrier Status: An HABS-HD Study
    (2022) Mai, Kevin; Petersen, Melissa; Hall, James; Johnson, Leigh; O'Bryant, Sid
    Background: The U.S. Hispanic population is projected to grow tremendously and face considerable increases in age-related conditions such as Alzheimer's Disease (AD). This same population also experiences a higher frequency of cerebrovascular conditions and diabetic risk factors, both of which have independently been associated with cognitive decline. Previous research demonstrates the impact of Diabetes Mellitus (DM) and white matter hyperintensities (WMHs) on cognitive functioning within the Hispanic population; however, to date, no study has looked into the effects of genetic factors such as APOE-e4 carrier status on the link between these medical conditions and cognition. Methods: Data were analyzed on Mexican American participants from a study of health disparities stratified by DM status (Yes/No) and WMH burden (Low/High): n = 696 APOE e4 non-carriers (n= 206 No DM/Low WMH, n= 73 Yes DM/Low WMH, n= 153 No DM/High WMH, n= 128 Yes DM/High WMH) and n = 157 APOE e4 carriers (n= 48 No DM/Low WMH, n= 17 Yes DM/Low WMH, n= 35 No DM/High WMH, n= 26 Yes DM/High WMH). All participants underwent cognitive testing and a medical exam. Neuropsychological test battery included Trail Making Test Part A and B, WMS-III Digit Span, Mini Mental Status Examination, Spanish and English Verbal Learning Test (Immediate and Delayed Recall), and Digit Symbol Substitution. Diagnosis of DM was categorized as "Yes/No" through past medical history and HbA1c blood work > 6.5. WMH status was based on a median value of 0.816 to separate "Low/High" burden. Genetic testing was completed for APOE e4 to determine carrier status. ANOVAs were conducted stratified by APOEe4 carrier status with medical condition group (Yes/No DM and Low/High WMH) entered as the predictor variable and cognitive test scores as the outcome variable. Tukey post-hoc tests were performed. Results: For APOE e4 non-carriers, participants in the Yes DM/Low WMH, No DM/High WMH, and Yes DM/High WMH groups performed worse than the No DM/Low WMH group on measures of attention, executive functioning, and processing speed. Those in the No DM/High WMH and Yes DM/High WMH groups also performed worse than the No DM/Low WMH group on measures of learning and memory. Among APOE e4 carriers, participants in the Yes DM/High WMH group performed worse than the Low DM/Low WMH group on measures of executive functioning, processing speed, immediate and delayed memory. Also, those in the Yes DM/High WMH group performed worse than the Yes DM/ Low WMH group on measures of global cognition, processing speed and delayed memory. Those in the No DM/ High WMH group performed worse than the No DM/Low WMH group in both immediate and delayed memory. Discussion: In APOE e4 carriers and non-carriers, DM and WMH burden were differentially associated with decreased test performance across multiple cognitive domains. This study tests the combined effect of DM and WMH on cognition in the context of APOE carrier status for Mexican Americans with findings that support the presence of specific associations thereby further highlighting the necessity to explore health disparities.
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    Practice Effect and Cardiorespiratory Response to Cognitive Test-Retest with Aging
    (2022) Reddy, Priyanka; Abdali, Kulsum; Ross, Sarah; Davis, Sandra; Shi, Xiangrong
    Background: This study aimed to examine the age-related difference in practice effect on cognitive performance and cardiorespiratory frequencies during test and retest with the same materials in different cognitive domains. Methods: Twenty cognitively normal older and younger men and women (65±2 vs 26±1 years old) provided the informed consent (approved by IRB) and participated in cognitive test and retest using Mini-Mental State Examination (MMSE), Digit-Span, Trail Making Test (TMT-B), and California Verbal Learning Test (CVLT-II) with ~3 weeks apart. During the testing, heart rate (HR) and breathing frequency (BF) were continuously monitored from electrocardiogram and plethysmograph. ANOVA was applied to examine the significance of the age and retest factors. Results: All cognitive performances were not affected by the age factor or the retest factor except CVLT-II. Baseline cognitive performances of the older vs younger groups were 27.7±1.1 vs 30.5±0.7 (P=0.034) in CVLT-II total Free-Recall, 29.2±0.4 vs 29.6±0.2 in MMSE, 15.6±1.6 vs 16.7±1.2 in Digit-Span, and 58.8±6.4 vs 48.0±3.6 in TMT-B, respectively. The retest factor only significantly improved total Free-Recall in the younger group (P=0.002). Baseline HR and BF were not different between the two groups, older vs younger: 72±5 vs 80±3 beats/min and 17±1 vs 16±1 breaths/min. Both HR and BF were significantly augmented (P< 0.01) in response to the cognitive test. However, both these responses were significantly attenuated during the retest (the retest factor P< 0.01). Only HR, not BF response was significantly affected by the age factor. Conclusions: There was no practice effect on cognitive performances in MMSE, Digit-Span, and TMT-B in both older and younger subjects. Total Free-Recall was significantly improved in the younger subjects only during the retest. There was a practice effect on the cardiorespiratory responses to cognitive challenge, which were significantly reduced during the cognitive retest. Aging significantly diminished HR response during cognitive challenge.
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    Visual Function and Cognitive Dysfunction in Older Adults
    (2022) Rashik, Mohammad Imran; Mozdbar, Sima; Aryal, Subhash; Johnson, Leigh; O'Bryant, Sid
    Background: Studies have shown a correlation between visual impairment and increased risk of Alzheimer's disease (AD). Therefore, it is important to understand the relationship between visual function and cognitive dysfunction in order to improve care and health-related quality of life. This study assesses the relationship between self-reported visual function and cognitive dysfunction through the use of two questionnaires, the Mini-Mental Status Exam (MMSE) and the 25 item National Eye Institute Vision Function Questionnaire (NEI VFQ-25). Methods: 131 participants from the Alzheimer's Disease in Primary Care (ADPC) study were recruited to complete the NEI VFQ-25. This questionnaire takes into account multiple domains of health and measures the impact of ocular dysfunction on each of the domains. Before completing the questionnaire, as part of the ADPC study, the subjects underwent neuroimaging and a battery of neuropsychological testing, including the MMSE. Based on clinical dementia rating scale (CDR), MMSE scores and additional cognitive testing, participants were classified into three groups of cognitive impairment. These were: normal control with no cognitive impairment (CDR sum of box score equaling 0), mild cognitive impairment (CDR sum of box score between 0.5 to 2) and Alzheimer's dementia (CDR sum of box score over 2.5). To examine the relationship between cognition and self-reported visual function, we performed a Kruskal Wallis test to assess vision specific role difficulties in the three diagnostic categories. Results: The Kruskal Wallis test revealed a significant difference in role difficulties related to vision among the three diagnostic groups (p = 0.04). This means that as the MMSE score decreased due to cognitive impairments, participants reported greater difficulties in their activities of daily living and completion of tasks due to deteriorating eyesight. Conclusions: An important component during the ophthalmic and neuropsychological evaluation of a patient is the consideration of visual function as it relates to quality of life. The need for the NEI-VFQ questionnaire arises because vision tests cannot comprehensively represent the emotional well-being or social function of a patient, formally known as the health-related quality of life. Identifying and addressing reduced visual function could play a role in improving the health-related quality of life for patients who are at an increased risk of cognitive dysfunction.
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    Association Between bilingualism and Amyloid Uptake Among Mexican Americans: An HABS-HD Study
    (2022) Wiley, Elizabeth; Johnson, Leigh; Hall, James; Petersen, Melissa; O'Bryant, Sid
    Background: Bilingualism is thought to provide protective benefits in regions of the brain associated with the onset of Alzheimer's Disease (AD). While there has been extensive research on bilingualism's effect on grey matter volume, there is no study to date that has examined the relationship between bilingualism and amyloid burden within brain regions characteristically impacted by AD. This study aims to fill this gap by comparing amyloid deposition in Mexican Americans who are either monolingual or bilingual. Methods: Data were analyzed on n=34 Hispanic, Mexican Americans (n=16 bilingual; n=18 monolingual) participants enrolled in a study of health disparities with available Amyloid PET scans. PET Amyloid scans were conducted using florbetaben (18F) on a Siemens Biograph Vision 450 whole-body PET/CT scanner. PET Amyloid SUVR levels were generated from the following Regions of Interest (ROIs): Frontal, Anterior Posterior Cingulate, Lateral Parietal, Lateral Temporal, and Global, with global SUVR>1.08 determined as the cut-off for Amyloid positivity. Independent t-test and chi-square tests were conducted to examine group differences in language status across demographic variables. One-way ANOVAs were conducted to examine groups differences in APOE e4 carrier status as well as in language capabilities (monolingual, bilingual) and PET amyloid SUVR. Follow-up analyses examining language capabilities were split by APOE e4 carrier status (carrier, non-carrier). Results: In comparison to APOE e4 non-carriers, APOE e4 carriers experienced significantly increased amyloid burden across all regional areas, including global (p< 0.05). Bilingual APOE e4 non-carriers showed a significantly increased amyloid deposition in the Anterior/Posterior Cingulate cortex in comparison to monolingual APOE e4 non-carriers. Furthermore, among APOE e4 non-carriers, there was a trend towards significance for global amyloid uptake (p=0.059), with bilinguals again showing higher amyloid burden. Among APOE e4 carriers, no significant associations were found between language status (monolingual, bilingual) and amyloid uptake. Discussion: This was the first study to examine the association between bilingualism and amyloid burden within specific cortical regions of the brain. Results contradicted previous work observing the role of the posterior/anterior cingulate in bilingualism. The trend towards significance in global amyloid uptake for APOE e4 non-carriers favored increased burden in bilinguals, a result opposite of what was expected. Bilingualism is complex and multifactorial and further work is greatly needed to understand the link it has with amyloid burden particularly by disease state.
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    Alzheimer's Disease Risk Allele Frequencies Differ Based on Ethnicity in HABLE Cohort
    (2022) Housini, Mohammad; Rao, Sumedha; Phillips, Nicole; O'Bryant, Sid; Barber, Robert C.
    Purpose: Alzheimer's Disease (AD) or other related dementias remain a significant burden on our aging population. Here we evaluate the top 10 AD risk alleles previously reported by Kunkle et al. (2018) in Mexican Americans and non-Hispanic whites enrolled in the Healthy Aging Brain in Latino Elders Study (HABLE) cohort to see if allele frequencies vary based on ethnicity. Methods: DNA was extracted from buffy coat samples (n = 1635) on the Hamilton robotic system with the Mag-Bind Blood & Tissue DNA HDQ 96 Kit. Genotyping was performed per manufacturer's protocol using the Illumina Infinium Global Screening Array (GSA) and analyzed with Genome Studio 2.0. Samples with call rates less than 98% were repeated or excluded. Allele and genotype frequencies were calculated using standard statistics by compiling the top ten AD risk alleles from Kunkle et al. (2018) and measuring their frequencies in the HABLE cohort. Results: Our data suggest varying degrees of allele and genotype frequencies among the top 10 risk conferring SNPs between Mexican Americans and Non-Hispanic Whites. In particular, we show some instances (BIN1, PTK2B) where the heterozygotes are in higher frequency than homozygotes. 8 of our evaluated SNPs show a difference greater than 5% between the two ethnicities. Conclusion: It may be beneficial to further study the top AD risk alleles among different ethnicities to determine if there are variable frequencies in those populations. We plan to expand and continue this work in other ethnicities and further elaborate on these differences to promote ethnicity targeted diagnostics and help reduce health disparities in medicine and science.
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    Role of DNA Methylation in Risk for Cognitive Impairment and Type 2 Diabetes in a Mexican American Cohort
    (2022) Daniel, Ann Abraham; Silzer, Talisa K.; Hall, Courtney; Sun, Jie; Zhou, Zhengyang; Phillips, Nicole; Barber, Robert C.
    Purpose: Alzheimer's disease (AD) and type 2 diabetes (T2D) are among the leading causes of mortality among the aging Mexican American population (≥ 65 years old) in the US. This cohort is expected to be the largest aging ethnic minority group in the US by 2050. In comparison to their non-Hispanic white counterparts who are most likely to develop AD associated with inflammation, aging Mexican Americans have an earlier onset of AD and metabolism related predisposition for AD. Mild cognitive impairment (MCI) is a phenotype that often leads to AD and is also prevalent in this cohort. The presence of T2D is known to double the risk of developing MCI/AD. The risk for AD, MCI and T2D is multifactorial, involving genetics and epigenetics. Methylation is a form of epigenetic regulation whereby a methyl group is added to the cytosine base in DNA. Methylation patterns in DNA can be affected and possibly reversed by a variety of environmental factors such as lifestyle and diet. Targeting changes to methylation patterns through associated lifestyle changes could be a possible prevention method for AD, MCI and T2D in the future, particularly for minority groups affected by health disparities, such as the Mexican American population. We aim to establish an epigenetic association between cognitive impairment (identified here as AD and MCI), and T2D that is unique to the Mexican American population. Methods: For this project, 551 aging participants from the Texas Alzheimer's Research and Care Consortium (TARCC) were selected, following quality control. A cross phenotype study design will be used to assess differential methylation associated with cognitive impairment (CI) alone, T2D alone and then with both CI and T2D simultaneously. For the first stage of this project, 299 Mexican American and 252 non-Hispanic white participants were stratified into groups of individuals diagnosed with CI alone and controls without CI within each ethnic group. In the second stage, this cohort will be stratified into individuals with T2D alone and controls without T2D. The third stage will stratify participants into those with both CI and T2D versus normal healthy controls. Lastly, any differential methylation associated with each ethnic group will be compared and contrasted. Peripheral blood drawn from participants was used to obtain individual methylation profiles using the Illumina Infinium MethylationEPIC chip array. Differential methylation will be assessed using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages in R. The Beta MIxture Quantile dilation (BMIQ) method will be used for data normalization. Results: Gene set enrichment and pathway analysis tools will be used to analyze results. Conclusions: Identifying methylation sites associated with CI and T2D could contribute towards developing biomarkers that are ethnicity-specific for the Mexican American population and possibly lead towards more effective medical treatment in the future.
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    Imputation Accuracy of Apolipoprotein E ε Alleles in Genome-wide arrays and real-time SNP Genotyping assays
    (2022) Subasinghe, Kumudu; Garlotte, Isabelle; O'Bryant, Sid E.; Barber, Robert C.; Phillips, Nicole
    Purpose: The vast majority of the established genetic-based risk for late-onset Alzheimer's disease (AD) is attributable to variation within the apolipoprotein E (APOE) gene. This gene, which encodes a protein implicated in various aspects of AD pathology, is characterized by two single nucleotide polymorphisms (SNPs; rs429358 and rs7412) that result in three distinct isoforms (ε4, ε3 and ε2). Most population-based genome-wide association studies to date have identified the APOE ε4 and ε2 alleles as the strongest genetic-based risk and protective factors for AD, respectively. APOE genotype is not only critical for determining disease risk and diagnosis, but also for developing individualized therapeutic strategies. Genotyping via real-time quantitative PCR (qPCR) is the gold standard for APOE isoform determination; however, if genome wide SNP data is available, imputation of APOE (i.e., probabilistic genotyping through inference) may eliminate the need for qPCR genotyping. In this project, we evaluate the concordance of APOE genotypes obtained via qPCR and a genome-wide SNP chip in non-Hispanic White and Mexican American individuals from the Health & Aging Brain among Latino Elders (HABLE) cohort. Method: DNA was extracted from buffy coat samples (n = 1650) on the Hamilton robotic system with the Mag-Bind Blood & Tissue DNA HDQ 96 Kit. qPCR was then performed using the TaqMan Genotyping Kit as per manufacturer's protocol. Results produced via qPCR were then compared to those imputed for rs429358 and directly typed for rs7412 on the Illumina Infinium Global Screening Arrays (GSA) and analyzed with Genome Studio 2.0. Samples with call rates less than 98% were repeated or excluded. Results: Concordance between the APOE genotypes obtained from qPCR and Infinium GSA was 99.32%. Discordance was likely due to poor sample quality and low-frequency imputation errors of rs429358, which may be corrected with more conservative thresholding of the imputed genotype confidence statistics. Conclusion: Genotype imputation from SNPs commonly typed in the APOE region is an effective method for APOE isoform determination, even in Mexican Americans who are more genetically heterogenous due to ancestral admixture; this method may be effectively implemented in large population-based studies of aging and AD.
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    Environmental Pesticide Exposure and Cognition Among Adults 60 Years and Older in the United States
    (2022) Starling, Jolie; Liu, Jialiang; Tao, Menghua
    Purpose: Cognitive decline is an increasingly important public health issue among elderly adults that can lead to loss of memory, decreased ability to function, and numerous other health burdens. Pesticides are commonly manufactured and distributed chemicals that are frequently used for occupational farming and within households. Pesticide exposure has been examined as a possible risk factor for cognitive decline in the past; however, a complete understanding of this relationship remains unclear. This study examined the association between pesticide exposure and cognition, taking into consideration the potential influence of lifestyle factors and comorbidities. Methods: Based on the nationally representative, 2011 - 2014 National Health and Nutrition Examination Survey (NHANES), the study included 733 participants aged greater than or equal to 60 years who completed cognition tests and had available data on urinary concentrations of six pyrethroid, herbicide, and organophosphate pesticide metabolites. Linear regression models were applied to examine the associations between pesticide exposure and cognition, measured by global cognitive z-score. Results: After adjusting for demographic and other confounding factors, a higher level of para-Nitrophenol was marginally associated with lower global cognitive z-score (β = -0.0761, 95% CI [-0.24, 0.09], highest vs. lowest tertile); however, the association was not statistically significant. When stratified, the association of 4-fluoro-3-phenoxy-benzoic acid with lower global cognition score was primarily observed among former smokers in the 0-50% detectable level (β = -0.3633, 95% CI [-0.68, -0.04]) and among the participants with a poverty income ratio (PIR) < 1.85 in both the 0-50% (β = -0.6678, 95% CI [-1.25, -0.09]) and 50-100% detectable levels (β = -0.3196, 95% CI [-0.62, -0.02]). The interactions with smoking and PIR status were statistically significant (p < 0.05). Among females, a higher level of para-Nitrophenol and both the 0-50% and 50-100% detectable levels of 4-fluoro-3-phenoxy-benzoic acid were marginally associated with lower global cognition; however, neither of these associations were statistically significant. There were no clear associations for global cognition with other pesticide metabolites. Conclusions: Our findings suggest that higher para-Nitrophenol exposure may associate with poor cognitive function in older adults. 4-fluoro-3-phenoxy-benzoic acid may impair cognition among former smokers and those with a PIR < 1.85. Future studies are needed to confirm the findings and to further understand mechanisms between pesticide exposure and cognitive decline.
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    Assessment of Mitochondrial DNA Damage in Cognitive Impairment via NGS: Health Disparities in Mexican Americans
    (2022) Reid, Danielle; Barber, Robert C.; Sun, Jie; Thorpe, Roland; Zhou, Zhengyang; Phillips, Nicole
    Mexican Americans (MAs) are the fastest growing subpopulation in the US, and as age increases, this population will be disproportionately affected by age-related diseases such as Alzheimer's disease (AD). Diabetes, stroke, depression, and obesity are common risk factors for developing cognitive impairment (CI) and may be of particular relevance to MAs due to their increased prevalence. MtDNA damage has been implicated in AD, and since metabolic comorbidities are more common in MAs, mtDNA damage and mitochondrial dysfunction may be related to the increased burden and earlier age-of-onset among MAs. Mitochondrial dysfunction can induce oxidative damage to guanosine (8oxoG) and cause DNA deletions, both of which have been well-documented in AD. The mitochondrial genome is particularly vulnerable to DNA damage, and age-associated decline in mitochondrial function results in accumulating reactive oxygen species capable of damaging essential biomolecules. We hypothesize that MAs incur mtDNA damage at an elevated rate due to increased comorbidity burden altering mitochondrial function. MtDNA from buffy coat and plasma samples of participants enrolled in the Texas Alzheimer's Research Care and Consortium were amplified using the RepliG mtDNA Amplification kit and were sequenced via NexteraXT on Illumina NextSeq. Somatic variants indicative of oxidative DNA damage and the commonly observed 5kb deletion were quantified in both the buffy coat mtDNA and ccf-mtDNA. These data were analyzed for association with CI and T2D in both the NHW and MA populations. Further, haplogroup-associated risk for mtDNA damage and ccf-mtDNA status was assessed. Our preliminary findings suggest clinical implications of oxidative mtDNA damage as a risk factor for CI specifically in MA females. These data highlight ethnic/racial differences in oxidative burden which may elucidate sex-specific mechanisms contributing to the manifestation of age-related disease etiology as AD, and the results may ultimately inform precision-based approaches to design therapeutics for mitigating AD disparities in the MA population.
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    Studying the Interplay Between Baseline Mental Health and Alzheimer's Disease Progression
    (2022) Rao, Sumedha; Housini, Mohammad; Royall, Donald; Palmer, Raymond; Barber, Robert C.
    Background: In aging adults, the most common form of dementia is Alzheimer's disease (AD). AD pathogenesis involves the accumulation of beta-amyloid (Aβ) protein aggregation in plaques and tau proteins in neurofibrillary tangles that are associated with a decreased number of synapses in the brain, altered neuronal function and cell death via neurotoxicity, as well as learning and memory deficits. Clinically, the presence and severity of neuropsychiatric symptoms that AD patients present with can be reliably measured by the Neuropsychiatric Inventory Questionnaire (NPIQ). This study aims to explore the association between baseline mental health and the severity of AD progression. Methods: To measure baseline mental health, NPIQ scores were used while the change in DeltaEq was used to represent the severity of AD progression within the TARCC cohort. DeltaEq is a homolog of Delta, a reliable latent dementia proxy that represents cognitive correlates of functional status and is specific for distinguishing cases with AD from other dementia-related presentations. Most crucially, the DeltaEq homolog has been adjusted for equivalence across ethnicities. Using stratified analysis and structured equation models, the association between baseline mental health and change in was investigated. Results: The first model exploring NPIQ and the change in DeltaEq was only adjusted for baseline eq; it showed NPIQ explaining 19% of the variance in delta DeltaEq and was statistically significant at p=0.016 for Non-Hispanic Whites. With the second model, age, sex, and education were adjusted for in addition to baseline eq. NPIQ was shown to explain 25% of the variance in delta DeltaEq while being statistically significant at p=0.037 for Non-Hispanic Whites. This model was replicated in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort; NPIQ was shown to be predictive for delta DeltaEq at p=0.013. Conclusion: In Non-Hispanic Whites, worse baseline mental health has been shown to predict increased severity and progression of AD. This makes it a clinical therapeutic target with the possible benefit of impacting the course of AD in patients. The fascinating interplay between mental health and its relationship to Alzheimer's disease should be studied further with an additional focus on ethnicity.
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    Sex Differences in Oxidative Stress Model of Prodromal Parkinson's Disease
    (2022) Mabry, Steve; Wilson, Elizabeth; Little, Joel; Romero, Steven; Cunningham, Rebecca
    INTRODUCTION: Parkinson's disease (PD) is an incurable neurodegenerative disorder that causes deterioration in motor and cognitive function and occurs more commonly in men. Gross motor impairment occurs after 60% dopaminergic neurons are lost in the substantia nigra brain region. However, it is unknown if sex differences are present in the prodromal stage of PD in which no dopaminergic neuronal loss or gross motor dysfunction are observed. Prodromal PD is associated with increased oxidative stress (OS) and OS damage in the substantia nigra, along with cognitive and fine motor skill dysfunction. To examine if sex differences are present in prodromal PD, we will use an animal model, chronic intermittent hypoxia (CIH), that recapitulates many prodromal PD characteristics. Our prior studies using male rats found that CIH induced global OS, OS damage in the substantia nigra, and cognitive dysfunction, which are all consistent with prodromal PD. METHODS: Adult male and female Sprague Dawley rats were exposed CIH to induce a prodromal PD phenotype. The CIH protocol consisted of 10 episodes of hypoxia (12% O2)/hour for a total of 8 hours/day over a 2-week period. Control rats were exposed to room air (normoxia). Rats were behaviorally tested for the following indexes during the last week of CIH exposure: 1) cognitive function (novel object recognition, Morris Water Maze), 2) fine motor behavior (modified open field with an elevated wire mesh), and 3) anxiety (marble test). At the conclusion of behavior testing, rats were sacrificed. Plasma and brain tissue was collected to examine oxidative stress. RESULTS: CIH increased circulating oxidized proteins in both male and female rats compared to control rats. No sex difference was observed in CIH induced circulating oxidative stress. Preliminary analysis indicate that sex differences are present in behavioral tests, especially cognitive function. CONCLUSIONS: These studies indicate sex differences in response to OS. CIH induced OS was consistent across both sexes, as evidenced by similar circulating OS levels. However, each sex responded (behaviorally) differently in response to CIH induced OS. These studies indicate that sex differences may be involved in prodromal PD. Knowledge of these sex differences could lead to earlier detection of PD and possibly the ability to slow conversion of prodromal PD to later stage PD that is exemplified by gross motor loss.