Aging / Alzheimer's Disease
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21646
Browse
Browsing Aging / Alzheimer's Disease by Author "Johnson, Leigh"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Epigenetic Risk Factors for Mild Cognitive Impairment, Alzheimer’s Disease and Metabolic Dysfunction in Mexican Americans(2018-03-14) Silzer, Talisa; Sun, Jie; Phillips, Nicole; Johnson, Leigh; O'Bryant, Sid; Barber, Robert C.; Abraham Daniel, AnnPurpose: Alzheimer’s is the most common form of dementia and the 5th leading cause of death for those over 651. The population of Mexican American elders will grow seven-fold by 20502 with rates of mild cognitive decline (MCI) and Alzheimer’s disease (AD) increasing exponentially1. Mexican Americans are diagnosed with MCI and AD at younger ages than non-Hispanic whites3; 4. In addition, Mexican Americans who are diagnosed with AD are 1) less likely to carry the ApoEε4 genotype3-5., 2) suffer a greater burden of type 2 diabetes3; 6, 3) experience greater metabolic-related cognitive decline7; 8 and 4) display a proteomic signature of AD that is heavily metabolic in nature4; 9, compared to non-Hispanic whites, whose proteomic signature for AD is dominated by inflammatory proteins. We hypothesized that differentially methylated regions of DNA (DMRs) are associated with age at onset of cognitive decline (MCI/AD) and metabolic dysfunction (metabolic syndrome/type 2 diabetes) in Mexican Americans. Methods: To test this hypothesis, we assayed genomic DNA methylation in samples from 14 female Mexican American participants enrolled in the Health and Aging Brain study in Latino Elders (HABLE). Participants were diagnosed with cognitive decline (n=4), metabolic dysfunction (n=3), both (n=4), or as a control (n=3). We isolated DNA from leukocytes and bisulfite treated the samples before running them on an Illumina MethylationEPIC chip in accordance with manufacturer’s recommendations to assay genomic DNA methylation. Results: Several interesting biological pathways showed significantly different methylation status between groups. When the participants were split on cognitive decline, DNA in the amyloid secretase, EGF receptor signaling, PDGF signaling, gonadotropin-releasing hormone receptor and Wnt signaling pathways were significantly hypermethylated in cases. In comparison, analyses based on metabolic dysfunction showed significant DNA hypomethylation in the beta1 and beta2 adrenergic receptor signaling pathways and hypomethylation of the gonadotropin releasing hormone receptor pathway in cases. Conclusions: The etiology of cognitive decline appears to differ between Mexican Americans and non-Hispanic whites. Future work will resolve how dementia risk differs between these and other ethnic groups. The knowledge gained from these studies will be critical to a better understanding of AD pathophysiology and the development of ethnicity-focused AD treatment options. Acknowledgements: Research reported here was supported by the National Institute On Aging of the National Institutes of Health under Award Number R01AG054073. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research team also thanks the local Fort Worth community and participants of the Health & Aging Brain Study.Item The relationship of Hypertension and related Cardiovascular Risk factors to Executive Functioning in Mexican-Americans(2018-03-14) Hall, James; Johnson, Leigh; O'Bryant, Sid; Vintimilla, RaulBackground: The effect of high blood pressure on cognitive domains is unclear but the literature suggests that the primary impact is on cognitive impairment in executive functions and slowing of mental processing speed. These cognitive functions are especially vulnerable to vascular change. Hispanics are at increased risk for cardiovascular disease, cognitive decline and dementias, and there is no sufficient literature about this relationship in this growing segment of the population. The purpose of this study was to examine the link between blood pressure and executive functioning in Mexican-Americans. Methods: Data were analyzed in 426 participants from the Health and Aging Brain Among Latino Elders study (HABLE). Cardiovascular disease (CVD) risks include hypertension, dyslipidemia, diabetes mellitus, and abdominal circumference over 40 inches. The presence of these risks was determined from self-report, use of medication, and lab results. Trails B was used as an index of executive function and entered as the dependent variable in the models. A one-way ANOVA was conducted to assess the effect of CVD risk factors on executive function. Linear regressions were utilized to examine the relationship between hypertension and other CVD risk factors with executive function. Age was entered as a covariate in the model. Results: Within the total sample, ANOVA revealed a statically significance difference between groups (F (4,495) = 3.15, p = .01). The post hoc tests showed that the individuals with two (M = 7.7, SD = 3.7), three (M = 7.4, SD = 3.9) or four (M = 6.9, SD = 3.6) risk factors differ significantly at p B = -1.6, 95% CI [-2.36, -.80], p = .00). Hypertension explained a 4% of variance in Trails B scores, (R2 = .04, F (1,398) = 15.78, p = .00). None of the other CVD risk were significant. Conclusion: Our findings suggested a relationship between diagnosis of hypertension and executive function in Mexican-Americans. No other CVD risk factors independently had a significant link with executive function. Having more than one CVD risks regardless of its nature was related to lower executive functioning. The results of this study support literature that suggested that the effects of high blood pressure on cognitive domains primarily involve executive functioning.