Browsing by Subject "cognitive impairment"
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Item APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba(Cambridge University Press, 2014-06) Hendrie, Hugh C.; Murrell, Jill; Baiyewu, Olusegun; Lane, Kathleen A.; Purnell, Christianna; Ogunniyi, Adesola; Unverzagt, Frederick W.; Hall, Kathleen; Callahan, Christopher M.; Saykin, Andrew J.; Gureje, Oye; Hake, Ann; Foroud, Tatiana; Gao, Sujuan; Department of Psychiatry, IU School of MedicineBackground There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer’s disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline. Methods In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox’s proportional hazards regression and mixed effects models. Results After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425). Conclusions In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.Item Association of Anticholinergic Burden with Cognitive Impairment and Health Care Utilization Among a Diverse Ambulatory Older Adult Population(Wiley, 2016-11) Campbell, Noll L.; Perkins, Anthony J.; Bradt, Pamela; Perk, Sinem; Wielage, Ronald C.; Boustani, Malaz A.; Ng, Daniel B.; Biostatistics, School of Public HealthStudy Objective To determine the association between Anticholinergic Cognitive Burden (ACB) score and both cognitive impairment and health care utilization among a diverse ambulatory older adult population. Design Retrospective cohort study. Data Source Medication exposure and other clinical data were extracted from the Regenstrief Medical Record System (RMRS), and cognitive diagnosis was derived from a dementia screening and diagnosis study. Patients A total of 3344 community-dwelling older adults (age 65 yrs and older) who were enrolled in a previously published dementia screening and diagnosis study; of these, 3127 were determined to have no cognitive impairment, and 217 were determined to have cognitive impairment. Measurements and Main Results The study followed a two-phase screening and comprehensive neuropsychiatric examination to determine a cognitive diagnosis, which defined cognitive impairment as dementia or mild cognitive impairment. The ACB scale was used to identify anticholinergics dispensed in the 12 months prior to screening. A total daily ACB score was calculated by using pharmacy dispensing data from RMRS; each anticholinergic was multiplied by 1, 2, or 3 consistent with anticholinergic burden defined by the ACB scale. The sum of all ACB medications was divided by the number of days with any medication dispensed to achieve the total daily ACB score. Health care utilization included visits to inpatient, outpatient, and the emergency department, and it was determined by using visit data from the RMRS. The overall population had a mean age of 71.5 years, 71% were female, and 58% were African American. Each 1-point increase in mean total daily ACB score was associated with increasing risk of cognitive impairment (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.004–1.27, p=0.043). Each 1-point increase in mean total daily ACB score increased the likelihood of inpatient admission (OR 1.11, 95% CI 1.02–1.29, p=0.014) and number of outpatient visits after adjusting for demographic characteristics, number of chronic conditions, and prior visit history (estimate 0.382, standard error [SE] 0.113; p=0.001). The number of visits to the emergency department was also significantly different after similar adjustments (estimate 0.046, SE 0.023, p=0.043). Conclusion Increasing total ACB score was correlated with an increased risk for cognitive impairment and more frequent health care utilization. Future work should study interventions that safely reduce ACB and evaluate the impact on brain health and health care costs.Item Cancer, Cognitive Impairment, and Work-Related Outcomes: An Integrative Review(ONS, 2016-09) Von Ah, Diane; Storey, Susan; Tallman, Eileen; Nielsen, Adele; Johns, Shelley A.; Pressler, Susan J.; IU School of NursingProblem Identification: Cancer survivors often report concerns regarding their memory, attention, and ability to process information and make decisions. These problems, which have also been demonstrated on objective neuropsychological assessments, may have a significant impact on work-related outcomes. Literature Search: A literature review was conducted using the following electronic databases: Ovid (MEDLINE®), PubMed, CINAHL®, and Web of Science. Search terms included cancer, survivors, cognitive, work, and work ability. Empirical research published in English from January 2002 to August 2015 that focused on cognitive impairment in adult cancer survivors was included in the review. Data Evaluation: Articles were evaluated by two independent researchers. Synthesis: Twenty-six studies met the inclusion criteria. Ten were qualitative, 15 were quantitative, and 1 had a mixed-methods design. Quantitative articles were synthesized using the integrative methodology strategies proposed by Whittemore and Knafl. Synthesis of qualitative articles was conducted using the criteria established by the Swedish Agency for Health Technology Assessment and Assessment of Social Services. Conclusions: To date, research in this context has been limited by cognitive assessments focusing primarily on patient self-assessments of attention, concentration, and memory. Additional research is needed to examine the impact of cognitive performance and to expand work-related outcomes measures to include perceived work ability, productivity, and actual performance. Implications for Nursing: Lack of information regarding cognitive impairment inhibits survivors’ ability to prepare, understand, and accept impending cognitive changes and how they may affect work ability. Oncology nurses can assist cancer survivors by preparing and educating them on how to better manage impairment associated with cancer and its treatment.Item Chronic consumption of a high-fat diet: investigation of negative consequences(2018-07) Vigil, Daniel W.; Boehm, StephenChronic consumption of a high-fat diet is a lifestyle factor that increases the risk for cognitive impairment (Granholm et al., 2008; Greenwood & Winocur, 2005; Mattson, 2004; Winocur & Greenwood, 2005). A high-fat diet appears to facilitate cognitive impairment through the promotion of insulin resistance (Greenwood & Winocur, 2005; Stranahan et al., 2008; Winocur & Greenwood, 2005). A gap in the literature is an established timeframe of the progression and underlying mechanism, which study in animals would better afford. Furthermore, A limited number of studies have investigated the relationship between a high-fat diet and behavioral dysregulation such as anxiety and depression. The 1st aim of the study was to determine if consumption of a high-fat diet leads to cognitive impairment and behavioral dysfunction at 3, 8, or 13 weeks of consumption. The 2nd aim was to determine if cholesterol levels and HBP activity are aberrantly increased in specific regions in mice that display feeding induced cognitive/behavioral dysfunction. Consumption of the experimental specialty diets produced a number of significant behavioral effects. These significant effects began to emerge after only 3 weeks of low-and high-fat feeding with increased anxiety-like behavior displayed higher in the high-fat diet group for the Elevated Plus Maze and Open Field Test. There was increased thigmotactic behavior and floating in the low-fat diet group in the Morris Water Maze (MWM) task, therefore making cognitive assessment uninterpretable. This pattern in the behavioral tasks were more robust in the 8 week group and alleviated in the 13 week group. There was only a significant difference in depression-like symptoms in the Forced Swim (FS) Task in the 3 week group. Cholesterol analysis is still under review in Dr. Elmendorf’s lab to correlate cholesterol levels and cognitive/behavioral impairment.Item Cognitive Changes Associated with Cancer and Cancer Treatment: State of the Science(ONS, 2015) Von Ah, Diane; School of NursingBackground: Cognitive impairment is a distressing, disruptive, and potentially debilitating symptom that can occur as a direct result of cancer or its treatment. National organizations have identified cognitive impairment as a challenge many survivors face and call for research to address this problem. Despite the priority, research is still relatively limited and questions remain unanswered about prevalence and impact on survivors, as well as coping strategies and effective treatment options available to address this potentially debilitating problem. Objectives: The purpose of this article is to (a) analyze the prevalence and types of cognitive impairment that commonly affect survivors; (b) delineate the impact that cognitive impairment after cancer and cancer treatment has on self-esteem, social relationships, work ability, and overall quality of life among survivors; and (c) synthesize and appraise commonly used coping strategies used by survivors to address cognitive impairment and evidence-based interventions that may be incorporated into clinical practice. Methods: A comprehensive review and synthesis of the literature was conducted. Findings: Evidence-based interventions to address cognitive changes after cancer and cancer treatment are limited. However, emerging research has demonstrated that nonpharmacologic treatments, such as cognitive training, are likely to be effective.Item Effects of EGCG Treatment of Ts65Dn Down Syndrome Mice on a Balance Beam Task(Office of the Vice Chancellor for Research, 2015-04-17) Taboada, Maria Fatima Delgado; Stringer, Megan; Roper, Randall J.; Goodlett, Charles R.Down syndrome (DS) is caused by trisomy of chromosome 21, and affects 1/700 live births. DS results in about 80 clinical phenotypes, including cognitive impairment. DYRK1A, a chromosome 21 gene, has been linked to alterations in morphology and function of the brain resulting in cognitive impairment. Epigallocatechin-3-gallate (EGCG), an inhibitor of DYRK1A activity, has been proposed as a possible treatment for cognitive deficits seen in individuals with DS. Using the Ts65Dn DS mouse model, we examined the effects of EGCG treatment on cerebellum dependent tasks using a balance beam test. We hypothesized that treatment with EGCG would improve Ts65Dn performance on the balance beam. In a first experiment, mice were given a dose of ~30 mg/kg/day EGCG, which showed no significant improvement in the balance beam task. In a second experiment, mice were given a dose of 100 mg/kg/day EGCG or water (control) starting at 3 weeks of age. The mice were handled two days before testing and then underwent a series of behavioral tasks including the balance beam test. The mice traversed three beams of differing widths (12, 9 and 6 mm), and three consecutive trials for each were recorded for further analysis. The balance beam recordings were scored by three independent scorers, blind to genotype and treatment, and the number of hind paw slips for each trial were scored. Our preliminary results indicate that the Ts65Dn mice are impaired at this task and have more hind paw slips compared to euploid controls. A larger number of animals should help to distinguish any differences in Ts65Dn mice due to EGCG treatment.Item Effects of Increased Dosage EGCG Treatment on Cognitive Deficits in the Ts65Dn Down Syndrome Mouse Model(Office of the Vice Chancellor for Research, 2015-04-17) Dhillon, Hardeep; Abeysekera, Irushi; Stringer, Megan; Goodlett, Charles R.; Roper, Randall J.Down syndrome (DS), caused by trisomy of human chromosome 21 (Hsa21), is the leading genetic cause of cognitive impairment and results in a constellation of phenotypes. Although symptomatic and therapeutic treatments exist for some DS phenotypes, treatments generally do not address the genetic etiology. The Ts65Dn mouse model, which contains a triplication of approximately half the gene orthologs of Hsa21, exhibits hippocampal learning and memory deficits as well as cerebellar motor and spatial deficits similar to those present in individuals with DS. DYRK1A, one of the genes overexpressed in DS, has been identified as a potential cause of cognitive impairment; therefore normalization of DYRK1A activity may be a valid form of treatment. We have shown that Epigallocatechin-3-gallate (EGCG), a major polyphenol of green tea, can rescue skeletal deficits found in the Ts65Dn mouse model at a low dosage. When this same low dosage was used to rescue behavioral deficits, however, it was ineffective. We hypothesize that high dose EGCG treatment lasting throughout the behavioral testing period will rescue the cognitive deficits observed in Ts65Dn mice. Trisomic mice and euploid littermates were given EGCG or water (control) for 7 weeks while being tested sequentially on novel object recognition (NOR) and Morris water maze (MWM). Our current data set shows that Ts65Dn mice exhibit deficits in learning and memory; further data will be collected in order to identify the effect of EGCG. Data showing pure EGCG as being ineffective will suggest the importance adding a supplemental compound, while data showing pure EGCG as an effective form of treatment will strongly support use of EGCG in translational studies in individuals with Down syndrome.Item Examining the ocular fundus in neurology(Wolters Kluwer, 2019-02) Rodenbeck, Stefanie J.; Mackay, Devin D.; Neurology, School of MedicinePurpose of review The funduscopic examination can be a technically difficult, and often omitted, portion of the neurologic examination, despite its great potential to influence patient care. Recent findings Medical practitioners are often first taught to examine the ocular fundus using a direct ophthalmoscope, however, this skill requires frequent practice. Nonmydriatic tabletop and portable fundus photography and even smartphone-based photography offer alternative and practical means for approaching examination of the ocular fundus. These alternative tools have been shown to be practical in a variety of settings including ambulatory clinics and emergency departments. Decreased retinal microvascular density detected with fundus photography has been linked to accelerated rates of cognitive decline. Research has also found optic disc pallor and retinopathy detected via fundus photography to be more prevalent in patients with recent stroke or transient ischemic attack. Summary Alternative methods of funduscopic examination based on fundus photography have the potential to improve the ease of use, portability, and availability of funduscopy. Recognition of changes in retinal microvasculature has the potential to noninvasively identify patients at the highest risk for cognitive impairment and cerebrovascular disease. However, further research is needed to determine the specific utility of measurements of retinal microvascular changes in clinical care. Innovative funduscopy techniques offer neurologists new approaches to this essential facet of the neurological examination.Item Program of Intensive Support in Emergency Departments for Care Partners of Cognitively Impaired Patients: Protocol for a Multisite Randomized Controlled Trial(JMIR, 2022-10) Chodosh, Joshua; Connor, Karen; Fowler, Nicole; Gao, Sujuan; Perkins, Anthony; Grudzen, Corita; Messina, Frank; Mangold, Michael; Smilowitz, Jessica; Boustani, Malaz; Borson, Soo; Medicine, School of MedicineBackground Older adults with cognitive impairment have more emergency department visits and 30-day readmissions and are more likely to die after visiting the emergency department than people without cognitive impairment. Emergency department providers frequently do not identify cognitive impairment. Use of cognitive screening tools, along with better understanding of root causes for emergency department visits, could equip health care teams with the knowledge needed to develop individually tailored care management strategies for post–emergency department care. By identifying and directly addressing patients’ and informal caregivers’ (or care partners’) psychosocial and health care needs, such strategies could reduce the need for repeat acute care. We have used the terms “caregiver” and “care partner” interchangeably. Objective We aimed to describe the protocol for a randomized controlled trial of a new care management intervention, the Program of Intensive Support in Emergency Departments for Care Partners of Cognitively Impaired Patients (POISED) trial, compared with usual care. We described the research design, intervention, outcome measures, data collection techniques, and analysis plans. Methods Emergency department patients who were aged ≥75 years and screened positive for cognitive impairment via either the Mini-Cog or the proxy-reported Short Informant Questionnaire on Cognitive Decline in the Elderly, with a planned discharge to home, were recruited to participate with their identified informal (family or friend) caregiver in the 2-site POISED randomized controlled trial at New York University Langone Health and Indiana University. The intervention group received 6 months of care management from the POISED Care Team of registered nurses and specialty-trained paraprofessionals, who perform root cause analyses, administer standardized assessments, provide advice, recommend appropriate referrals, and, when applicable, implement dementia-specific comorbid condition protocols. The control group received care as recommended at emergency department discharge (usual care) and were given information about resources for further cognitive assessment. The primary outcome is repeat emergency department use; secondary outcomes include caregiver activation for patient health care management, caregiver depression, anxiety, and experience of social support as important predisposing and time-varying enabling and need characteristics. Data were collected from questionnaires and patients’ electronic health records. Results Recruitment was conducted between March 2018 and May 2021. Study findings will be published in peer-reviewed journals and presented to peer audiences, decision makers, stakeholders, and other interested persons. Conclusions The POISED intervention is a promising approach to tailoring care management based on root causes for emergency department admission of patients with cognitive impairment with the aim of reducing readmissions. This trial will provide insights for caregivers and emergency department and primary care providers on appropriate, personalized, and proactive treatment plans for older adults with cognitive impairment. The findings will be relevant to audiences concerned with quality of life for individuals with cognitive impairment and their caregivers. Trial Registration ClinicalTrials.gov NCT03325608; https://clinicaltrials.gov/ct2/show/NCT03325608 International Registered Report Identifier (IRRID) DERR1-10.2196/36607Item Relationship between African-American Race and Delirium in the Intensive Care Unit(Wolters Kluwer, 2016-09) Khan, Babar A.; Perkins, Anthony; Hui, Siu L.; Gao, Sujuan; Campbell, Noll L.; Farber, Mark O.; Boustani, Malaz A.; Medicine, School of MedicineObjective Delirium is a highly prevalent syndrome of acute brain dysfunction among critically ill patients that has been linked to multiple risk factors such as age, pre-existing cognitive impairment, and use of sedatives; but to date the relationship between race and delirium is unclear. We conducted this study to identify whether African-American race is a risk factor for developing ICU delirium. Design A prospective cohort study. Setting Medical and Surgical ICUs of a university affiliated, safety-net hospital in Indianapolis, Indiana. Patients 2087 consecutive admissions with 1008 African-Americans admitted to the ICU services from May 2009 to August 2012. Interventions None Measurements and Main Results Incident delirium defined as first positive Confusion Assessment Method for the ICU (CAM-ICU) result after an initial negative CAM-ICU; and prevalent delirium defined as positive CAM-ICU on first CAM-ICU assessment. The overall incident delirium rate in African-Americans was 8.7% compared to 10.4% in Caucasians (P: 0.26). The prevalent delirium rate was 14% in both African-Americans and Caucasians (P: 0.95). Significant age and race interactions were detected for incident delirium (P: 0.02), but not for prevalent delirium (P: 0.3). The hazard ratio for incident delirium for African-Americans in the 18–49 years age group compared to Caucasians of similar age was 0.4 (0.1– 0.9). The hazard and odds ratios for incident and prevalent delirium in other groups were not different. Conclusions African-American race does not confer any additional risk for developing incident or prevalent delirium in the ICU. Instead younger African-Americans tend to have lower rates of incident delirium compared to similar age Caucasians.