Glycemic Control and Dementia: The Role of Pharmacotherapy and Vascular Complications

血糖控制和痴呆：药物治疗和血管并发症的作用

• 批准号: 10557206
• 负责人: Paola Gilsanz
• 金额: $ 38.94万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557206
• 关键词: Acute; Address; Adult; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Attenuated; Blood Vessels; California; Characteristics; Complications of Diabetes Mellitus; Data; Dementia; Development; Diabetes Mellitus; Elderly; Epidemic; Etiology; Event; Exposure to; Future; Glycosylated hemoglobin A; Goals; Guidelines; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Impaired cognition; Individual; Insulin; Integrated Delivery of Health Care; Intervention; Knowledge; Learning; Link; Longitudinal Studies; Measures; Medical Records; Metabolic; Metformin; Microvascular Dysfunction; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Patients; Pattern; Persons; Pharmacotherapy; Population; Populations at Risk; Prevalence; Prevention approach; Public Health; Registries; Research; Risk; Risk Factors; Risk Reduction; Role; Sample Size; Severities; Statistical Methods; Subgroup; Sulfonylurea Compounds; System; Techniques; Therapeutic; Thiazolidinediones; Time; Variant; Vulnerable Populations; aging brain; causal model; clinical care; clinical practice; clinical translation; cognitive benefits; cognitive function; cohort; comorbidity; contextual factors; cost effective; dementia risk; diabetes mellitus therapy; glycemic control; high risk; human old age (65+); improved; innovation; insight; longitudinal analysis; macrovascular disease; member; modifiable risk; mortality; older patient; protective factors; risk mitigation

ABSTRACT Approximately 25% of Americans over the age of 65 are living with diabetes (~12 million individuals), over 90% of which is type 2 diabetes, and the prevalence is expected to increase. Elderly individuals with type 2 diabetes have 50-100% higher risk of Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) yet it remains unclear how to best mitigate this risk. From a public health standpoint it is imperative to evaluate potential risk and protective factors for AD/ADRD in this vulnerable population. There is some evidence that glycemic control and diabetes treatments play a role in AD/ADRD risk but studies in natural settings are need to identifying time-varying characteristics of long-term glycemic control associated with elevated AD/ADRD risk into consideration important contextual factors such comorbidities and diabetes pharmacotherapy. Our long-term goal is to identify modifiable risk factors of AD/ADRD risk among individuals with type 2 diabetes and to help inform interventions and clinical practice aimed at improving healthy brain aging among this at-risk population. We propose an innovative use of the Kaiser Permanente Northern California Diabetes Registry encompassing data collected from 1994-2018+ in over 115,000 elderly people with type 2 diabetes to engender a better understanding of the role of glycemic control and diabetes pharmacotherapy on AD/ADRD risk. The specific aims of the proposal are to: 1) Determine the longitudinal association between long-term glycemic control and risk of AD/ADRD in a large cohort of elderly individuals with type 2 diabetes and identify which patterns are most protective or harmful for AD/ADRD risk; 2) Understand the time-dependent interplay between micro- and macrovascular complications and long-term glycemic control on AD/ADRD risk; and 3) Evaluate the association between anti-hyperglycemic therapies (e.g. sulfonylureas, metformin, thiazolidinediones, insulins) and risk of AD/ADRD while accounting for long-term glycemic control. Findings from the proposal will be directly inform treatment targets and therapeutic management of geriatric patients with diabetes, an increasing portion of our elderly population at high risk of AD/ADRD.

摘要 大约25%的65岁以上的美国人患有糖尿病(约1200万人)，其中90%以上是2型糖尿病，而且患病率预计还会增加。患有2型糖尿病的老年人患阿尔茨海默病和阿尔茨海默病相关痴呆(AD/ADRD)的风险高出50%-100%，但如何最好地减轻这一风险仍不清楚。从公共卫生的角度来看，必须评估这一脆弱人群中AD/ADRD的潜在风险和保护因素。有一些证据表明血糖控制和糖尿病治疗在AD/ADRD风险中起作用，但在自然环境中的研究需要确定与AD/ADRD风险升高相关的长期血糖控制的时变特征，并考虑到重要的背景因素，如合并症和糖尿病药物治疗。我们的长期目标是在2型糖尿病患者中确定AD/ADRD风险的可改变的危险因素，并帮助提供旨在改善这一高危人群中健康脑老化的干预措施和临床实践。我们建议创新性地使用Kaiser Permanente North California糖尿病登记系统，包括1994-2018+年收集的超过115,000名老年2型糖尿病患者的数据，以更好地了解血糖控制和糖尿病药物治疗对AD/ADRD风险的作用。该建议的具体目的是：1)确定在一大批老年2型糖尿病患者中长期血糖控制与AD/ADRD风险之间的纵向关联，并确定哪些模式对AD/ADRD风险最具保护或有害；2)了解微血管和大血管并发症与长期血糖控制对AD/ADRD风险的依赖关系；以及3)在考虑长期血糖控制的同时，评估抗高血糖疗法(如磺脲类、二甲双胍、噻唑烷二酮类、胰岛素)与AD/ADRD风险的关联。该提案的结果将直接为老年糖尿病患者的治疗目标和治疗管理提供信息，老年糖尿病患者在AD/ADRD的高危老年人口中所占比例越来越大。