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.

抽象的 65岁以上的美国人中约有25％患有糖尿病（约1200万人），其中90％以上是2型糖尿病，预计患病率将增加。 2型糖尿病患者患阿尔茨海默氏病的风险高50-100％，而阿尔茨海默氏病与疾病相关的痴呆症（AD/ADRD）的风险更高，但仍不清楚如何最好地减轻这种风险。从公共卫生的角度来看，必须评估该脆弱人群中AD/ADRD的潜在风险和受保护因素。有证据表明，血糖控制和糖尿病治疗在AD/ADRD风险中起作用，但是需要在自然环境中进行研究，以确定与升高的AD/ADRD风险相关的长期血糖控制的时间变化特征，以考虑重要的上下文因素，例如合并症和糖尿病药物治疗。我们的长期目标是确定2型糖尿病患者中AD/ADRD风险的可修改风险因素，并有助于为干预措施和临床实践提供信息，旨在改善这种高危人群中健康的大脑衰老。我们提出了北加州北加州糖尿病登记处的创新使用，其中包括1994 - 2018年以上收集的数据，其中超过115,000名老年患有2型糖尿病的人，以更好地了解血糖控制和糖尿病在AD/ADRD风险中的药物治疗的作用。该提案的具体目的是：1）确定在大量患有2型糖尿病的基本人群中长期血糖控制与AD/ADRD风险之间的纵向关联，并确定哪些模式对AD/ADRD风险最受保护或有害； 2）了解微血管并发症和大血管并发症之间的时间依赖性相互作用以及对AD/ADRD风险的长期血糖控制； 3）评估抗血糖疗法（例如磺酰氟菌，二甲双胍，噻唑烷二酮，胰岛素）与AD/ADRD风险之间的关联，同时考虑长期血糖控制。该提案的发现将直接告知治疗靶标的老年糖尿病患者的治疗靶标和治疗管理，这是我们老年人口中越来越多的AD/ADRD风险。