Browsing by Subject "Risk factor"
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Item Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference(Wiley, 2024) Kloske, Courtney M.; Belloy, Michael E.; Blue, Elizabeth E.; Bowman, Gregory R.; Carrillo, Maria C.; Chen, Xiaoying; Chiba-Falek, Ornit; Davis, Albert A.; Di Paolo, Gilbert; Garretti, Francesca; Gate, David; Golden, Lesley R.; Heinecke, Jay W.; Herz, Joachim; Huang, Yadong; Iadecola, Costantino; Johnson, Lance A.; Kanekiyo, Takahisa; Karch, Celeste M.; Khvorova, Anastasia; Koppes-den Hertog, Sascha J.; Lamb, Bruce T.; Lawler, Paige E.; Le Guen, Yann; Litvinchuk, Alexandra; Liu, Chia-Chen; Mahinrad, Simin; Marcora, Edoardo; Marino, Claudia; Michaelson, Danny M.; Miller, Justin J.; Morganti, Josh M.; Narayan, Priyanka S.; Naslavsky, Michel S.; Oosthoek, Marlies; Ramachandran, Kapil V.; Ramakrishnan, Abhirami; Raulin, Ana-Caroline; Robert, Aiko; Saleh, Rasha N. M.; Sexton, Claire; Shah, Nilomi; Shue, Francis; Sible, Isabel J.; Soranno, Andrea; Strickland, Michael R.; Tcw, Julia; Thierry, Manon; Tsai, Li-Huei; Tuckey, Ryan A.; Ulrich, Jason D.; van der Kant, Rik; Wang, Na; Wellington, Cheryl L.; Weninger, Stacie C.; Yassine, Hussein N.; Zhao, Na; Bu, Guojun; Goate, Alison M.; Holtzman, David M.; Neurology, School of MedicineIntroduction: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. Methods: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. Results: This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. Discussion: Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. Highlights: APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.Item Differential effects of risk factors on the cognitive trajectory of early- and late-onset Alzheimer’s disease(BMC, 2021-06-14) Kim, Jaeho; Woo, Sook-Young; Kim, Seonwoo; Jang, Hyemin; Kim, Junpyo; Kim, Jisun; Kang, Sung Hoon; Na, Duk L.; Chin, Juhee; Apostolova, Liana G.; Seo, Sang Won; Kim, Hee Jin; Neurology, School of MedicineBackground: Although few studies have shown that risk factors for Alzheimer's disease (AD) are associated with cognitive decline in AD, not much is known whether the impact of risk factors differs between early-onset AD (EOAD, symptom onset < 65 years of age) versus late-onset AD (LOAD). Therefore, we evaluated whether the impact of Alzheimer's disease (AD) risk factors on cognitive trajectories differ in EOAD and LOAD. Methods: We followed-up 193 EOAD and 476 LOAD patients without known autosomal dominant AD mutation for 32.3 ± 23.2 months. Mixed-effects model analyses were performed to evaluate the effects of APOE ε4, low education, hypertension, diabetes, dyslipidemia, and obesity on cognitive trajectories. Results: APOE ε4 carriers showed slower cognitive decline in general cognitive function, language, and memory domains than APOE ε4 carriers in EOAD but not in LOAD. Although patients with low education showed slower cognitive decline than patients with high education in both EOAD and LOAD, the effect was stronger in EOAD, specifically in frontal-executive function. Patients with hypertension showed faster cognitive decline than did patients without hypertension in frontal-executive and general cognitive function in LOAD but not in EOAD. Patients with obesity showed slower decline in general cognitive function than non-obese patients in EOAD but not in LOAD. Conclusions: Known risk factors for AD were associated with slower cognitive decline in EOAD but rapid cognitive decline in LOAD.Item Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea(Springer Nature, 2024-04-25) Chun, Min Young; Chae, Wonjeong; Seo, Sang Won; Jang, Hyemin; Yun, Jihwan; Na, Duk L.; Kang, Dongwoo; Lee, Jungkuk; Hammers, Dustin B.; Apostolova, Liana G.; Jang, Sung-In; Kim, Hee Jin; Neurology, School of MedicineBackground: Early-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear. We aimed to investigate how hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and osteoporosis influence the development and mortality of EOD and LOD, respectively. Methods: Using the Korean National Health Insurance Service (NHIS) database, we collected 546,709 dementia-free individuals and followed up for 11 years. In the two study groups, the Younger group (< 65 years old) and the Older group (≥ 65 years old), we applied Cox proportional hazard models to assess risk factors for development of EOD and LOD, respectively. Then, we assessed risk factors for mortality among EOD and LOD. Results: Diabetes mellitus and osteoporosis increased the risk of EOD and LOD development. Hypertension increased the risk of EOD, while atrial fibrillation increased the risk of LOD. Conversely, hyperlipidemia exhibited a protective effect against LOD development. Additionally, diabetes mellitus increased mortality in EOD and LOD. Hypertension and atrial fibrillation increased mortality in LOD, while hyperlipidemia decreased mortality in EOD and LOD. Conclusions: Risk factors influencing dementia development and mortality differed in EOD and LOD. Targeted public health interventions addressing age-related risk factors may reduce dementia incidence and mortality.Item Empowering At-Risk Youth Through Open Studio: Developing an Evaluation Tool to Assess Empowerment(2017) Holdren, Erica; Misluk, Eileen; King, JulietAn integrative literature review was used to understand how an open studio approach in art therapy is used with at-risk youth to increase empowerment. The following concepts were explored: risk and protective factors in adolescence, open studio approach in art therapy, psychological empowerment, and self-reporting evaluation tools. Risk and protective factors include family and peer dynamics, educational opportunities, and communication skills. These factors are influential in the development of empowerment. Empowerment is defined as having control over one’s life, the ability to identify needs and resources, and the ability to take action. The open studio approach in art therapy supported adolescents by providing them a space to engage in creative experiences that work to build a sense of empowerment. The researcher further synthesized this data to design an evaluation tool to assess how at-risk youth are empowered by participating in the open studio approach to art therapy. The evaluation tool for at-risk adolescents can be used as a guide for therapists to address the protective factors of empowerment and the effectiveness of the open studio approach. This tool can be used as a means to gain the necessary data to demonstrate the efficacy of a studio based approach in art therapy for empowering at-risk youth.Item Genetically-predicted placental gene expression is associated with birthweight and adult body mass index(Springer Nature, 2023-01-06) Jasper, Elizabeth A.; Hellwege, Jacklyn N.; Piekos, Jacqueline A.; Jones, Sarah H.; Hartmann, Katherine E.; Mautz, Brian; Aronoff, David M.; Edwards, Todd L.; Velez Edwards, Digna R.; Medicine, School of MedicineThe placenta is critical to human growth and development and has been implicated in health outcomes. Understanding the mechanisms through which the placenta influences perinatal and later-life outcomes requires further investigation. We evaluated the relationships between birthweight and adult body mass index (BMI) and genetically-predicted gene expression in human placenta. Birthweight genome-wide association summary statistics were obtained from the Early Growth Genetics Consortium (N = 298,142). Adult BMI summary statistics were obtained from the GIANT consortium (N = 681,275). We used S-PrediXcan to evaluate associations between the outcomes and predicted gene expression in placental tissue and, to identify genes where placental expression was exclusively associated with the outcomes, compared to 48 other tissues (GTEx v7). We identified 24 genes where predicted placental expression was significantly associated with birthweight, 15 of which were not associated with birthweight in any other tissue. One of these genes has been previously linked to birthweight. Analyses identified 182 genes where placental expression was associated with adult BMI, 110 were not associated with BMI in any other tissue. Eleven genes that had placental gene expression levels exclusively associated with BMI have been previously associated with BMI. Expression of a single gene, PAX4, was associated with both outcomes exclusively in the placenta. Inter-individual variation of gene expression in placental tissue may contribute to observed variation in birthweight and adult BMI, supporting developmental origins hypothesis.Item Impact of Social Vulnerability on Comorbid Cancer and Cardiovascular Disease Mortality in the United States(Elsevier, 2022-09-20) Ganatra, Sarju; Dani, Sourbha S.; Kumar, Ashish; Khan, Safi U.; Wadhera, Rishi; Neilan, Tomas G.; Thavendiranathan, Paaladinesh; Barac, Ana; Hermann, Joerg; Leja, Monika; Deswal, Anita; Fradley, Michael; Liu, Jennifer E.; Sadler, Diego; Asnani, Aarti; Baldassarre, Lauren A.; Gupta, Dipti; Yang, Eric; Guha, Avirup; Brown, Sherry-Ann; Stevens, Jennifer; Hayek, Salim S.; Porter, Charles; Kalra, Ankur; Baron, Suzanne J.; Ky, Bonnie; Virani, Salim S.; Kazi, Dhruv; Nasir, Khurram; Nohria, Anju; Medicine, School of MedicineBackground: Racial and social disparities exist in outcomes related to cancer and cardiovascular disease (CVD). Objectives: The aim of this cross-sectional study was to study the impact of social vulnerability on mortality attributed to comorbid cancer and CVD. Methods: The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database (2015-2019) was used to obtain county-level mortality data attributed to cancer, CVD, and comorbid cancer and CVD. County-level social vulnerability index (SVI) data (2014-2018) were obtained from the CDC's Agency for Toxic Substances and Disease Registry. SVI percentiles were generated for each county and aggregated to form SVI quartiles. Age-adjusted mortality rates (AAMRs) were estimated and compared across SVI quartiles to assess the impact of social vulnerability on mortality related to cancer, CVD, and comorbid cancer and CVD. Results: The AAMR for comorbid cancer and CVD was 47.75 (95% CI: 47.66-47.85) per 100,000 person-years, with higher mortality in counties with greater social vulnerability. AAMRs for cancer and CVD were also significantly greater in counties with the highest SVIs. However, the proportional increase in mortality between the highest and lowest SVI counties was greater for comorbid cancer and CVD than for either cancer or CVD alone. Adults <45 years of age, women, Asian and Pacific Islanders, and Hispanics had the highest relative increase in comorbid cancer and CVD mortality between the fourth and first SVI quartiles, without significant urban-rural differences. Conclusions: Comorbid cancer and CVD mortality increased in counties with higher social vulnerability. Improved education, resource allocation, and targeted public health interventions are needed to address inequities in cardio-oncology.Item Lipoprotein(a) and risk of cognitive impairment in Black and White Americans: the Reasons for Geographic and Racial Differences in Stroke cohort(Elsevier, 2023-08-08) Rentería, Miguel Arce; McClure, Leslie A.; Callas, Peter W.; LaBode-Richman, Vanessa M.; Kroll, Danielle S.; Manly, Jennifer J.; Kroll, Danielle S.; Manly, Jennifer J.; Zakai, Neil A.; Unverzagt, Frederick; Cushman, Mary; Psychiatry, School of MedicineBackground: Cognitive impairment has a substantial vascular etiology. Higher lipoprotein(a) [Lp(a)] is associated with cardiovascular disease risk, but its association with cognitive function is uncertain. We hypothesized that Lp(a) is a risk factor for cognitive impairment, a relationship that would be modified by race and sex. Objectives: To study the association of Lp(a) with cognitive impairment in a biracial cohort. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 Black and White Americans aged >45 years from 2003 to 2007. After 3.4 years, among participants with normal baseline cognition, baseline Lp(a) was measured in 434 cases of incident cognitive impairment and 557 controls. Cognitive impairment was defined as scores below the sixth percentile based on age, sex, race, and education norms on 2 or 3 components of a 3-test battery administered every 2 years. Results: Median Lp(a) was higher in Black than in White individuals. Among Black participants, the adjusted odds ratio (OR) of cognitive impairment per SD higher increment Lp(a) was 1.39 (95% CI: 1.05, 1.84). The OR in White participants was 1.03 (95% CI: 0.87, 1.21; P for race difference = .03). The relationship of Lp(a) with cognitive trajectory differed by sex and race. Elevated Lp(a) was associated with worse baseline memory in Black men and a steeper trajectory of verbal fluency decline in Black men than in White men and women. Conclusion: Higher Lp(a) was associated with increased risk of cognitive impairment in Black but not White individuals. Future studies should evaluate the biological and social mechanisms through which race and Lp(a) interact to increase risk of cognitive impairment.Item Molecular Mechanisms Linking Risk Factors to Cholangiocarcinoma Development(MDPI, 2022) Ceci, Ludovica; Zhou, Tianhao; Lenci, Ilaria; Meadows, Vik; Kennedy, Lindsey; Li, Ping; Ekser, Burcin; Milana, Martina; Zhang, Wenjun; Wu, Chaodong; Sato, Keisaku; Chakraborty, Sanjukta; Glaser, Shannon S.; Francis, Heather; Alpini, Gianfranco; Baiocchi, Leonardo; Medicine, School of MedicineThe poor prognosis of cholangiocarcinoma in humans is related to several factors, such as (i) the heterogeneity of the disease, (ii) the late onset of symptoms and (iii) the limited comprehension of the carcinogenic pathways determining neoplastic changes, which all limit the pursuit of appropriate treatment. Several risk factors have been recognized, including different infective, immune-mediated, and dysmorphogenic disorders of the biliary tree. In this review, we report the details of possible mechanisms that lead a specific premalignant pathological condition to become cholangiocarcinoma. For instance, during liver fluke infection, factors secreted from the worms may play a major role in pathogenesis. In primary sclerosing cholangitis, deregulation of histamine and bile-acid signaling may determine important changes in cellular pathways. The study of these molecular events may also shed some light on the pathogenesis of sporadic (unrelated to risk factors) forms of cholangiocarcinoma, which represent the majority (nearly 75%) of cases.Item Prevalence, incidence, and natural history of HPV infection in adult women ages 24 to 45 participating in a vaccine trial(Elsevier, 2020-05-25) Ferris, Daron G.; Brown, Darron R.; Giuliano, Anna R.; Myers, Evan; Joura, Elmar A.; Garland, Suzanne M.; Kjaer, Susanne K.; Perez, Gonzalo; Saah, Alfred; Luxembourg, Alain; Velicer, Christine; Medicine, School of MedicineObjectives The natural history of human papillomavirus (HPV) infection has been studied extensively in young women; this study investigated HPV infection in adult women. Methods Data from 3817 women aged 24–45 years in a global trial of the 4-valent HPV (6/11/16/18) vaccine were used to calculate prevalence of anogenital infections containing 9-valent (9v) HPV vaccine types (6/11/16/18/31/33/45/52/58) and five non-vaccine types (35/39/51/56/59). Incidence of infections and persistent infections was estimated for 989 placebo recipients naive to all 14 HPV types at baseline. Age-adjusted hazard ratios were calculated for various sociodemographic factors. Results Prevalence of anogenital infection was highest in France at 29.2% (9vHPV types) and 21.7% (non-vaccine types) and lowest in the Philippines at 7.6% (9vHPV types) and 5.1% (non-vaccine types). Overall, HPV incidence (per 100 person-years) was 5.2 (9vHPV types) and 4.7 (non-vaccine types), and incidence of persistent infection was 2.7 (9vHPV types) and 2.1 (non-vaccine types). Factors associated with new HPV infections included younger age, younger age at first intercourse, being single, current use of tobacco, and higher number of past and recent sex partners. Conclusions Because mid-adult women acquire new HPV infections, administration of the 9vHPV vaccine could reduce HPV-related morbidity and mortality in this population.