Inflammation, long-term diabetes characteristics, and cognitive decline

描述（由申请人提供）：这项为期5年的前瞻性研究将研究长期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名认知完好（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）精神病学部门、以色列示巴医疗中心精神病学部门和以色列第二大卫生组织马卡比卫生服务（MHS）社区卫生部门合作完成的。它向具有代表性的170万以色列公民提供保健服务，其中11 000人在特拉维夫地区患有糖尿病，年龄在65岁以上。研究这一人群的好处是：a)从极其丰富的MHS糖尿病登记处获得长达10年的数据，包括HbA1c、抗糖尿病和其他药物、疾病持续时间、高血压和其他糖尿病相关特征；b)完全计算机化的集中处理MHS病历，便于数据访问和分析；c)患者免费使用MHS中心实验室进行分析，确保完全使用；d)从MHS药房获得大量补贴药物，记录每一次购买（与处方药物的主题报告相反）；e)尽量减少接触损失，因为病人由卫生保健部门照顾；f)通过终止客户资助来及时通知死亡。Sheba的痴呆症诊断程序将与MSSM阿尔茨海默病研究中心（ADRC）的诊断程序完全整合。每隔18个月对受试者进行随访。除了完整的MHS实验室和医学数据外，包括以色列和ADRC医生在内的诊断共识远程会议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)长期血糖控制不良，3)糖尿病药物，特别是二甲双胍，以及4)MRI异常对认知能力下降率的影响。此外，将检查炎症或MRI异常对血糖控制或糖尿病药物使用与认知结果的关联的贡献。除了调查糖尿病认知能力下降的关系外，确定炎症的影响——一个可改变的危险因素——在这种关系中，对普通人群中早期痴呆的潜在机制有影响，并可以为未来具有潜在巨大公共卫生影响的干预研究提供基础。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损害中的致病或促进作用。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、糖尿病药物使用和脑异常对认知能力下降率的影响。最终，我们的目标是在不损害认知的情况下延长寿命。这项研究将指出干预措施，以帮助糖尿病患者，谁是痴呆的高风险。由于糖尿病和痴呆症的发病率正在不成比例地增加，特别是随着人口结构向老年化的强烈转变，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痴呆症的机制具有重要意义，这可能导致对认知衰退和痴呆症的更广泛的预防或姑息性干预。

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.