Inflammation, long-term diabetes characteristics, and cognitive decline

描述(申请人提供)：这项为期5年的前瞻性研究将考察长期的2型糖尿病特征和炎症如何影响居住在以色列特拉维夫的1000名认知正常(在招募时)65岁及以上的糖尿病患者的认知能力下降的发展。这项研究是由纽约西奈山医学院(MSSM)的精神病学系、以色列Sheba医学中心的精神病学系和以色列第二大保健组织Maccabi Health Services(MHS)的社区卫生部合作进行的。它为具有代表性的170万以色列公民提供医疗保健，其中11000人患有糖尿病，在特拉维夫地区年龄在65岁以上。研究这一人群的好处是：a)来自非常丰富的MHS糖尿病注册中心的长达10年的数据，包括HbA1c、抗糖尿病和其他药物、病程、高血压和其他糖尿病相关特征；b)完全计算机化的中央处理的MHS医疗记录，便于数据访问和分析；c)MHS中央实验室对患者的分析免费，确保完全使用；d)MHS药房提供大量补贴的药物，记录每次购买的药物(与指定药物的报告相反)；e)联系的损失最小，因为患者由MHS护理；以及f)通过结束客户资金来及时通知死亡。Sheba的痴呆症诊断程序将与MSSM阿尔茨海默病研究中心(ADRC)的程序完全整合。受试者将每隔18个月进行一次跟踪调查。包括以色列和ADRC医生在内的诊断共识电话会议除了完整的MHS实验室和医疗数据外，还将收集该项目收集的临床、神经心理学和MRI数据。将收集DNA，并制定数据共享计划。具体目的是调查基线1)炎症，2)长期血糖控制不佳，3)糖尿病药物，特别是二甲双胍，以及4)MRI异常对认知功能减退率的影响。此外，还将研究炎症或MRI异常对血糖控制或糖尿病药物使用与认知结果之间的关系的影响。除了研究糖尿病认知功能下降的关系外，确定炎症--一种可改变的风险因素--在这种关系中的影响，对普通人群中早期痴呆的潜在机制有影响，并可能为未来的干预研究提供基础，具有潜在的重大公共卫生影响。证明大脑异常如何将糖尿病特征与认知能力下降联系起来，将支持这些特征在认知妥协中的因果或促成作用。公共卫生相关性：这项针对糖尿病患者的研究将调查炎症、血糖控制不良、糖尿病药物的使用以及基线水平的脑异常对认知功能减退率的影响。最终，我们的目标是在认知上不妥协的情况下延长寿命。这项研究将指向帮助糖尿病患者的干预措施，这些患者是痴呆症的高危人群。由于糖尿病和痴呆症的发病率正在不成比例地增加，特别是在人口结构向老年人强烈转变的情况下，这项研究有望对公共卫生产生重大影响。此外，确定炎症和大脑异常对认知障碍风险的影响对普通人群中的痴呆症机制有影响，这可能导致对认知能力下降和痴呆症进行更广泛的预防性或姑息性干预。

DESCRIPTION (provided by applicant): This prospective 5-year study will examine how long-term type 2 diabetes characteristics and inflammation affect the development of cognitive decline in a cohort of 1000 cognitively intact (at recruitment) diabetic individuals 65 years and older living in Tel-Aviv, Israel. This study is a collaboration of the Department of Psychiatry at the Mount Sinai School of Medicine (MSSM), NY, the Department of Psychiatry at the Sheba Medical Center, Israel, and the Department of Community Health of the Maccabi Health Services (MHS), the second largest HMO in Israel. It provides health care to a representative cross section of 1.7 million Israeli citizens, 11,000 of whom have diabetes and are above the age of 65 in the area of Tel-Aviv. The benefits of studying this population are: a) up to 10 years of data from the extraordinarily rich MHS Diabetes Registry, including HbA1c, anti-diabetic and other medication, duration of disease, hypertension and other diabetes related characteristics; b) fully computerized centrally processed MHS medical records, facilitating data access and analysis; c) no charge to patients for analyses by the MHS centralized laboratory, ensuring complete use; d) significantly subsidized medication from MHS pharmacies, which record every purchase (in contrast to subject report of medication prescribed); e) minimal loss to contact since ill subjects are cared for by MHS; and f) prompt death notification by ending of client funding. The dementia diagnostic procedures at Sheba will be fully integrated with those of the MSSM Alzheimer's Disease Research Center (ADRC). Subjects will be followed at 18-month intervals. Diagnostic consensus teleconferences including both Israeli and ADRC physicians will have clinical, neuropsychological, and MRI data collected by this project in addition to complete MHS laboratory and medical data. DNA will be collected and a data sharing plan is in place. The specific aims are to investigate the impact of baseline 1) inflammation, 2) poor long-term glycemic control, 3) diabetes medication, specifically metformin, and 4) MRI abnormalities, on the rate of cognitive decline. Additionally, the contribution of inflammation or MRI abnormalities to the associations of glycemic control or diabetes medication use with cognitive outcomes will be examined. Beyond investigating the relationship of cognitive decline in diabetes, identifying the impact of inflammation-a modifiable risk factor-within this relationship, has implications for mechanisms underlying incipient dementia in the general population, and could provide the basis for future intervention studies with potential great public health impact. Demonstrating how brain abnormalities link diabetes characteristics to cognitive decline would support a causative or contributive role of these characteristics in cognitive compromise. PUBLIC HEALTH RELEVANCE: This study of diabetic individuals will investigate the roles of inflammation, poor glycemic control, use of diabetes medications, and brain abnormalities at baseline on the rates of cognitive decline. Ultimately, our goal is to extend life without cognitive compromise. This study will point to interventions to assist individuals with diabetes, who are at high risk for dementia. Since rates of diabetes and dementia are disproportionately increasing, especially so as the population structure shifts strongly toward the aged, this study can be expected to have major public health implications. Furthermore, identifying the impact of inflammation and brain abnormalities on risk for cognitive impairment has implications for mechanisms of dementia in the general population, which may lead to even broader based preventive or palliative interventions for cognitive decline and dementia.