Predictors of Late-life Cognitive Health in Type 1 Diabetes

描述（由申请人提供）：1型糖尿病（T1 D）是一种复杂的疾病，需要持续坚持血糖目标，并对血糖进行细致的关注和警惕。虽然发病率在增加，但平均预期寿命为69岁，比20年前观察到的54岁增加了15岁。伴随着寿命的延长，患者可以存活到认知障碍和痴呆的高风险年龄，这两者都极大地影响了糖尿病管理和自我护理。老年2型糖尿病患者（T2 D）的认知障碍风险是血糖正常个体的两倍，但目前尚不清楚老年T1 D患者是否也有更大的风险，以及影响和调节因素是什么。T1 D儿童、青少年和中年人在认知功能的某些领域中显示出缺陷（5），但是缺乏关于60岁或60岁以上个体的认知的信息。与老年T2 D患者相比，T1 D具有更年轻的发病年龄和更长的糖尿病持续时间、增加的低血糖、更多的微血管并发症但更少的大血管并发症，并且根据定义，都用胰岛素均匀治疗。在T2 D人群中，低血糖发作、抑郁和微血管合并症是认知功能障碍的既定风险因素。然而，尚不清楚这些因素（在T1 D中常见2-3倍）如何影响老年T1 D人群的认知老化。我们提出了一个创新的纵向研究认知老化的老年T1 D，这将关闭差距的知识，在这个快速增长的群体中的晚年认知功能。我们将利用北方加州凯泽医疗机构（KPNC）糖尿病登记处的精美数据资源。该登记研究包括超过147，000名60岁及以上的老年糖尿病患者（>7000名潜在的1型糖尿病患者），从中抽样并前瞻性地调查这一未充分研究和独特群体的神经心理功能和认知变化概况。我们将招募1200例年龄在60-80岁之间的患者（600例T1 D患者和600例无糖尿病患者），并在匹配队列研究中随访4年以上。在基线和36个月后，将提供详细的神经心理成套测试，并通过每年电话管理的整体认知收集进行补充。我们的目标如下：1）。确定老年1型糖尿病患者与匹配的无糖尿病老年个体组相比的整体和领域特异性认知的基线和三年变化，2。在1型糖尿病的背景下，描述血糖控制和血管并发症对认知变化的作用; 3.）评估抑郁症和1型糖尿病对认知变化的相互作用。这将是第一个关于1型糖尿病认知老化的纵向研究，对血糖治疗目标和自我护理具有深远的临床意义。它还将提供一个 认知障碍和痴呆预防中血糖和胰岛素相关机制的机制框架

DESCRIPTION (provided by applicant): Type 1 diabetes (T1D) is a complicated disease requiring constant adherence to glycemic targets and meticulous attention and vigilance of blood sugar. Although it is increasing in incidence the average life expectancy is 69 years, a 15 year increase from age 54 observed two decades ago. Concomitant with increased longevity is survival to an age at high risk of cognitive impairment and dementia both which greatly impact diabetes management and self-care. Elderly type 2 diabetes patients (T2D) have double the risk of cognitive impairment than normoglycemic individuals, yet it's unknown whether older T1D individuals are also at greater risk, and what the contributing and modulating factors are. T1D children, adolescents and middle- aged adults show deficits in certain domains of cognitive function (5), yet there's a lack of information regarding cognition in individuals aged 60 or older In contrast to elderly T2D patients, T1D have a much younger age of onset and longer duration of diabetes, increased hypoglycemia, more microvascular but less macrovascular complications, and by definition, are homogeneously treated with insulin. In the T2D population, hypoglycemic episodes, depression and microvascular comorbidities are established risk factors for cognitive impairment. Yet, it is unknown how these factors (2-3 times more common in T1D) influence cognitive aging in elderly T1D populations. We propose an innovative longitudinal study of cognitive aging in elderly T1D which will close the gap in knowledge regarding late-life cognitive function in this rapidly increasing group. We will exploit the exquisite data resources o the Kaiser Permanente of Northern California (KPNC) Diabetes Registry. The registry comprises over 147,000 elderly individuals with diabetes aged 60 and older (>7000 potential individuals with type 1 diabetes) from which to sample and prospectively investigate neuropsychological function and the profile of cognitive changes in this understudied and unique group. We will recruit 1200 patients aged 60-80 years (600 T1D and 600 without diabetes) and follow them over 4 years in a matched cohort study. At baseline and 36 months later a detailed neuropsychological battery will be given, and supplemented by annual phone administered collection of global cognition. Our goals are the following:1). Determine baseline and three year changes in global and domain specific cognition in elderly type 1 diabetes patients in comparison to a matched group of elderly individuals without diabetes, 2.) Characterize the role of glycemic control and vascular complications on cognitive change in the context of type 1 diabetes, and 3.) Evaluate the interaction of depression and type 1 diabetes on cognitive changes. This would be the first longitudinal study of cognitive aging in type 1 diabetes and has profound clinical implications for glycemic treatment targets and self-care. It will also provide a mechanistic framework for understanding glycemic and insulin related mechanisms in prevention of cognitive impairment and dementia