The Risk of Developing Alzheimer's Disease and Related Dementias Associated with Hypertension, Diabetes, and Drug Therapies for Cancer: Up to 30-year Follow-up for Older Medicare Beneficiaries

与高血压、糖尿病和癌症药物治疗相关的阿尔茨海默病和相关痴呆症的风险：对老年医疗保险受益人长达 30 年的随访

• 批准号: 9975450
• 负责人: XIANGLIN DU
• 金额: $ 31.07万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9975450
• 关键词: Accounting; Address; Adult; Affect; Age; Age-associated memory impairment; Alzheimer' s Disease; Alzheimer' s disease related dementia; Antidiabetic Drugs; Antihypertensive Agents; Antineoplastic Agents; Area; Attention Concentration; Breast; Cancer Patient; Cause of Death; Child; Clinical Trials; Cognition; Cognitive; Cohort Studies; Colorectal; Confidence Intervals; Cranial Irradiation; Craniocerebral Trauma; Data; Databases; Dementia; Diabetes Mellitus; Diagnosis; Disease; Education; Ethnic Origin; Gender; Geographic Locations; Goals; High Prevalence; Hypertension; Impaired cognition; Incidence; Intervention Trial; Joints; Language; Late Effects; Link; Malignant Neoplasms; Medical Records; Medicare; Medicare claim; Memory; Mental disorders; Monitor; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Population; Prevalence; Prevention strategy; Prostate; Race; Recording of previous events; Reporting; Research; Research Personnel; Resources; Risk; Risk Factors; SEER Program; Sampling; Testing; Time; United States; Variant; Vascular Diseases; aged; anti-cancer; beneficiary; blood pressure intervention; blood pressure regulation; cancer diagnosis; cancer therapy; chemotherapy; cohort; comorbidity; dementia risk; design; diabetes mellitus therapy; effective therapy; follow-up; hazard; lung small cell carcinoma; malignant breast neoplasm; mild cognitive impairment; prevent; public health relevance; randomized trial; skills; social; trend; vascular factor

Abstract The prevalence of Alzheimer’s disease (AD) and related dementias (ADRD) has been increasing over the past few decades and is projected to double by 2025 and triple by 2050. AD is still incurable, and causes of ADRD remain largely unknown, but they have been linked to many risk factors, including age, education, history of psychiatric disorders, head trauma, and vascular diseases or related risk factors. More recently, antihypertensive and antidiabetic drug therapies have been associated with a lower risk of developing dementia and early cognitive impairment. In 2019, a large clinical trial reported that intensive blood pressure control significantly reduced the risk of mild cognitive impairment and was the first trial to demonstrate an effective strategy for the prevention of age-related cognitive impairment. Given a high prevalence of hypertension and diabetes in the adult population, the utilization of disease-modifying drugs may provide an effective strategy for the prevention of ADRD. However, there is no large cohort study monitoring and assessing the joint effects of antihypertensive, antidiabetic, and anticancer medications on the risk of ADRD. Medicare, which has covered a large population aged 65 or older in the U.S. since 1965 with comprehensive and well-documented electronic databases available since 1991 (including anticancer chemotherapy), provides a great opportunity and resource to monitor the prevalence and incidence of ADRD over time. In addition, since Medicare Part-D comprehensive drug coverage was implemented in 2006, it is possible to determine the impact of antihypertensive and antidiabetic drugs on the risk of these dementias. Hence, the primary goal of this proposed study is to test the hypothesis that anticancer, antihypertensive and antidiabetic drug therapies have impacted the prevalence and incidence of ADRD over the past 30 years. To accomplish this, we propose to address the following Specific Aims: 1) to determine the secular trends in the prevalence of ADRD from 1991 to 2020 among Medicare beneficiaries aged 65 or older in the United States and variations in the prevalence of ADRD by state, geographic region, age, gender, race/ethnicity, and comorbidity; 2) to determine the incidence of developing ADRD in association with vascular factors and other potential risk factors among Medicare beneficiaries who were free of dementia at baseline and followed for up to 30 years; 3) to determine the association between a cancer diagnosis and anticancer drug therapies and the risk of developing ADRD by comparing a large cohort of patients diagnosed with major cancers to those with similar background risks but without cancer in 1991-2020; and 4) to determine the independent and joint effects of antihypertensive, antidiabetic and anticancer drug therapies on the risk of developing ADRD among Medicare beneficiaries aged 65 or older in 2007-2020 after Medicare Part-D comprehensive drug data became available. The findings from this study will have significant implications for preventing or delaying the onset of ADRD and hence will make substantial contributions to the primary research goal of the National Alzheimer’s Project Act by 2025.

抽象的 阿尔茨海默氏病（AD）和相关痴呆症（ADRD）的患病率一直在增加 几十年来，预计到2025年将翻一番，到2050年三倍。 仍然在很大程度上未知，但它们与许多风险因素有关，包括年龄，教育，历史 精神疾病，头部创伤和血管疾病或相关危险因素。最近，降压性 和抗糖尿病药物疗法与患痴呆症和早期疾病的风险较低有关 认知障碍。 2019年，一项大型临床试验报告说，密集的血压控制明显 降低了轻度认知障碍的风险，是第一个证明了有效策略的试验 预防与年龄相关的认知障碍。鉴于高血压和糖尿病患病率很高 成人人群，利用疾病改良药物可能为预防提供有效的策略 Adrd。但是，没有大量的队列研究监测和评估降压的关节作用， 抗糖尿病和抗癌药物的风险。 Medicare，覆盖了大量人口 自1965年以来，美国65岁或65岁以上，拥有全面且有据可查的电子数据库 自1991年以来（包括抗癌化疗），提供了一个很好的机会和资源来监视 随着时间的流逝，ADRD的患病率和事件。此外，由于Medicare零件D综合药物覆盖范围 于2006年实施，可以确定降压药和抗糖尿病药对 这些痴呆症的风险。因此，这项拟议的研究的主要目标是检验以下假设。 抗癌，抗高血压和抗糖尿病药物疗法影响了 在过去30年中。为此，我们建议解决以下特定目的：1） 确定1991年至2020年ADRD患病率的世俗趋势 在美国65岁以上，以及国家，地理区域，年龄，年龄，ADRD患病率的差异 性别，种族/种族和合并症； 2）确定与 在没有痴呆症的医疗保险受益人中，血管因素和其他潜在危险因素 基线，最多30年； 3）确定癌症诊断与 抗癌药物疗法和通过比较大量诊断的患者来发展ADRD的风险 患有背景风险相似但在1991 - 2020年没有癌症的人的主要癌症； 4）确定 降压，抗糖尿病和抗癌药物疗法的独立和关节作用对 在Medicare Part-D之后，2007 - 2020年65岁或65岁的Medicare受益人之间发展ADRD 全面的药物数据可用。这项研究的发现将对 防止或延迟ADRD的发作并因此将为主要研究做出重大贡献 到2025年，《国家阿尔茨海默氏症计划法》的目标。