Review of Associations of Diabetes and Insulin Resistance With Brain Health in Three Harmonised Cohort Studies of Ageing and Dementia

IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Roshni Biswas, Ana W. Capuano, Rupal I. Mehta, Lisa L. Barnes, David A. Bennett, Zoe Arvanitakis
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Abstract

Diabetes increases the risk of dementia, and insulin resistance (IR) has emerged as a potential unifying feature. Here, we review published findings over the past 2 decades on the relation of diabetes and IR to brain health, including those related to cognition and neuropathology, in the Religious Orders Study, the Rush Memory and Aging Project, and the Minority Aging Research Study (ROS/MAP/MARS), three harmonised cohort studies of ageing and dementia at the Rush Alzheimer's Disease Center (RADC). A wide range of participant data, including information on medical conditions such as diabetes and neuropsychological tests, as well as other clinical and laboratory-based data collected annually. Neuropathology data are collected in participants who agree to autopsy at death. Recent studies have measured additional peripheral and brain IR data, including multi-omics. This review summarises findings from the RADC cohort studies that investigate the relation of diabetes and IR in older adults to cognition, neuropathology, omics in dementia, and other brain health measures. Examining the risk of clinically diagnosed dementia in older adults, our study found a 65% increased risk of Alzheimer's disease (AD) dementia in individuals with diabetes compared with those without. Regarding cognitive function, we have consistently observed associations of diabetes, as well as both peripheral and brain IR, with worse and declining performance in global cognition and specific cognitive domains, particularly semantic memory and perceptual speed. Studies utilising neuropathological data showed associations of diabetes and peripheral IR with brain infarcts, while brain IR measures, notably alpha serine/threonine-protein kinase1 (AKT1), were associated with both brain infarcts and AD pathology. Multi-omics studies suggested shared causal genes and pathways between diabetes and dementia. Recent epigenetic studies have revealed associations between IR and AD risk, along with distinct 5-hydroxymethylcytosine signatures in diabetes-associated AD. Furthermore, our studies have utilised other available data to investigate the impact of diabetes on neurological outcomes other than cognition and reported worsening of parkinsonian-like signs in diabetes. Recent studies have also explored risk factors for diabetes and have reported associations between lower literacy and decision-making abilities with elevated haemoglobin A1C levels, a peripheral IR measure. Overall, our findings, as summarised in this review, illustrate a range of mechanistic and other insights into the complex relationship of diabetes and IR with brain health. These findings may have important implications for future research on the ageing brain, including the prevention of cognitive decline and dementia in persons at risk for or with diabetes.

Abstract Image

糖尿病和胰岛素抵抗与脑健康在三个老龄化和痴呆协调队列研究中的关系综述
糖尿病增加痴呆的风险,而胰岛素抵抗(IR)已成为一个潜在的统一特征。在这里,我们回顾了过去20年来发表的关于糖尿病和IR与大脑健康关系的研究结果,包括与认知和神经病理学相关的研究结果,这些研究结果来自拉什阿尔茨海默病中心(RADC)的宗教秩序研究、拉什记忆和衰老项目和少数民族衰老研究(ROS/MAP/MARS),这三项关于衰老和痴呆的协调队列研究。广泛的参与者数据,包括关于糖尿病和神经心理测试等医疗状况的信息,以及每年收集的其他临床和实验室数据。神经病理学数据收集于同意在死亡时进行尸检的参与者。最近的研究测量了额外的外周和大脑红外数据,包括多组学。本综述总结了RADC队列研究的结果,这些研究调查了老年人糖尿病和IR与认知、神经病理学、痴呆组学和其他脑健康指标的关系。通过对老年人临床诊断为痴呆的风险进行检查,我们的研究发现,与没有糖尿病的人相比,糖尿病患者患阿尔茨海默病(AD)痴呆的风险增加了65%。关于认知功能,我们一直观察到糖尿病以及外周和大脑IR与整体认知和特定认知领域的表现恶化和下降有关,特别是语义记忆和感知速度。利用神经病理学数据的研究显示,糖尿病和外周IR与脑梗死有关,而脑IR测量,特别是α -丝氨酸/苏氨酸蛋白激酶(AKT1),与脑梗死和AD病理均相关。多组学研究表明,糖尿病和痴呆之间有共同的致病基因和途径。最近的表观遗传学研究揭示了IR与AD风险之间的关联,以及糖尿病相关AD中明显的5-羟甲基胞嘧啶特征。此外,我们的研究利用了其他可用的数据来调查糖尿病对认知以外的神经系统预后的影响,并报告了糖尿病中帕金森样症状的恶化。最近的研究也探讨了糖尿病的危险因素,并报道了低文化水平和决策能力与血红蛋白A1C水平升高(一种外周IR指标)之间的联系。总的来说,我们的研究结果,总结在这篇综述中,说明了糖尿病和IR与大脑健康的复杂关系的一系列机制和其他见解。这些发现可能对未来关于大脑老化的研究具有重要意义,包括预防有糖尿病风险或患有糖尿病的人的认知能力下降和痴呆。
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来源期刊
Diabetes/Metabolism Research and Reviews
Diabetes/Metabolism Research and Reviews 医学-内分泌学与代谢
CiteScore
17.20
自引率
2.50%
发文量
84
审稿时长
4-8 weeks
期刊介绍: Diabetes/Metabolism Research and Reviews is a premier endocrinology and metabolism journal esteemed by clinicians and researchers alike. Encompassing a wide spectrum of topics including diabetes, endocrinology, metabolism, and obesity, the journal eagerly accepts submissions ranging from clinical studies to basic and translational research, as well as reviews exploring historical progress, controversial issues, and prominent opinions in the field. Join us in advancing knowledge and understanding in the realm of diabetes and metabolism.
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