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: 10348750
• 负责人: XIANGLIN DU
• 金额: $ 31.2万
• 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/10348750
• 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 control; blood pressure intervention; 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 过去，阿尔茨海默病（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 年将增加两倍。AD 仍然无法治愈，ADRD 的原因 仍然很大程度上未知，但它们与许多风险因素有关，包括年龄、教育程度、病史 精神疾病、头部外伤、血管疾病或相关危险因素。 抗糖尿病药物治疗与降低患痴呆症和早期痴呆的风险有关 2019年，一项大型临床试验报告称，强化血压控制可显着改善认知障碍。 降低了轻度认知障碍的风险，并且是第一个证明有效策略的试验 鉴于高血压和糖尿病的患病率很高，预防与年龄相关的认知障碍。 对于成年人群，使用缓解疾病的药物可能为预防提供有效的策略 然而，目前还没有大型队列研究来监测和评估抗高血压药物的联合作用。 抗糖尿病和抗癌药物对 ADRD 风险的影响，已覆盖大量人群。 自 1965 年以来在美国年满 65 岁且拥有全面且记录齐全的电子数据库 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测 此外，自 Medicare Part-D 全面药物承保以来，ADRD 的患病率和发病率随时间变化。 于 2006 年实施，可以确定抗高血压和抗糖尿病药物对 因此，这项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治疗影响了该病的患病率和发病率 过去 30 年来的 ADRD 为实现这一目标，我们建议实现以下具体目标： 1) 确定 1991 年至 2020 年老年医疗保险受益人中 ADRD 患病率的长期趋势 美国 65 岁或以上的老年人以及 ADRD 患病率因州、地理区域、年龄、 性别、种族/民族和合并症；2) 确定与 ADRD 相关的发生率 未患痴呆症的医疗保险受益人中的血管因素和其他潜在危险因素 基线并随访长达 30 年；3) 确定癌症诊断与癌症之间的关联 通过比较大量确诊患者来了解抗癌药物疗法和发生 ADRD 的风险 1991-2020 年患有主要癌症的人与具有相似背景风险但未患癌症的人进行比较；4) 确定 抗高血压、抗糖尿病和抗癌药物治疗对风险的独立和联合影响 2007 年至 2020 年 Medicare Part-D 后，65 岁或以上的 Medicare 受益人中出现 ADRD 这项研究的结果将对全面的药物数据产生重大影响。 预防或延缓 ADRD 的发生，因此将为初步研究做出重大贡献 到 2025 年，国家阿尔茨海默病项目法案的目标。