Predictors of Late-life Cognitive Health in Type 1 Diabetes

描述（申请人提供）：1型糖尿病（Type 1 diabetes, T1D）是一种复杂的疾病，需要持续坚持血糖指标，并对血糖进行高度关注和警惕。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。伴随寿命延长的是活到认知障碍和痴呆高风险的年龄，这两者都极大地影响了糖尿病的管理和自我保健。老年2型糖尿病患者（T2D）发生认知障碍的风险是血糖正常者的两倍，但尚不清楚老年T1D患者是否也有更大的风险，以及影响和调节因素是什么。T1D儿童、青少年和中年人在某些认知功能领域表现出缺陷(5)，但关于60岁及以上人群的认知方面的信息缺乏。与老年T2D患者相比，T1D患者发病年龄更年轻，糖尿病持续时间更长，低血糖发生率更高，微血管并发症更多，但大血管并发症更少，并且根据定义，可以均匀地使用胰岛素治疗。在T2D人群中，低血糖发作、抑郁和微血管合并症是认知障碍的危险因素。然而，尚不清楚这些因素（在T1D中常见2-3倍）如何影响老年T1D人群的认知衰老。我们提出了一项创新性的纵向研究老年T1D的认知衰老，这将缩小对这个快速增长的群体的晚年认知功能的知识差距。我们将利用北加州凯撒医疗机构（KPNC）糖尿病登记的精致数据资源。该登记处包括超过147,000名60岁及以上的老年糖尿病患者（bbb7000名潜在的1型糖尿病患者），从中取样并前瞻性地研究这一未被充分研究的独特群体的神经心理功能和认知变化概况。我们将招募1200名年龄在60-80岁之间的患者（600名糖尿病患者和600名非糖尿病患者），并在匹配队列研究中随访4年以上。在基线和36个月后，将给予详细的神经心理学测试，并辅以年度电话管理的全球认知收集。我们的目标是：1)。确定老年1型糖尿病患者与匹配组无糖尿病老年人的总体认知和领域特异性认知的基线和三年变化，2)。2 .描述1型糖尿病患者血糖控制和血管并发症在认知改变中的作用。评估抑郁症和1型糖尿病对认知改变的相互作用。这将是第一次对1型糖尿病患者认知衰老的纵向研究，对血糖治疗目标和自我保健具有深远的临床意义。它也会提供

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