EFFECTS OF GLYCOXIDATION ON COGNITION

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。这个年轻研究者试点项目将研究糖氧化（晚期糖基化终末产物，AGE）对非痴呆老年参与者样本认知的影响，并为更大规模的纵向研究奠定基础。 AGE 被提议用来解释为什么年龄和糖尿病是 AD 的危险因素。尽管如此，AGEs 从未被前瞻性地研究为认知能力下降的危险因素。特别是，由于 AGE 可以通过饮食来改变，因此它们是后续预防和治疗研究中非常令人兴奋的潜在候选者。 拟议的研究将建立在一项正在进行的纵向研究（PI- Helen Vlassara 博士 - 西奈山医学院老年病学系糖尿病和老龄化部门主任）的基础上，该研究检查 60 岁以上受试者循环 AGE 和（饮食）AGE 摄入量、氧化应激标志物、炎症标志物和血管功能障碍之间的年龄依赖性关系。在拟议的研究中，将通过临床痴呆评定量表、MMSE 和西奈山阿尔茨海默病研究中心 (ADRC) 的广泛神经心理学电池，并由 ADRC 共识诊断会议在基线和随访中进行评估。此外，在基线时，我们将收集 DNA 用于 APOE 和未来的遗传学研究。 这项研究的结果可能会将 AGE 确定为一种新的可改变的环境风险因素，与内源性机制共同作用，对认知产生负面影响。这项自然横断面和纵向研究有可能支持未来的干预措施，以减少 AGE 的影响，预防或延缓患痴呆症和 AD 风险增加的老年人的认知能力下降。 假设： 1- 主要假设：AGE 水平较高的受试者在基线时会表现出较差的认知功能。 2-探索性假设：具有较高基线 AGE 或随时间推移 AGE 增加较大的受试者将表现出更大程度的认知下降。 3-探索性假设：APOE4 将强化假设 1 中的假设关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This young investigator pilot project will examine the effects of glycoxidation (advanced glycation end products, AGEs) on cognition in a sample of non-demented elderly participants and lay the foundation for a larger longitudinal study. AGEs have been proposed as an explanation why age and diabetes are risk factors for AD. Nonetheless, AGEs have never been studied prospectively as a risk factor for cognitive decline. Particularly, since they are modifiable by diet, AGEs are very exciting potential candidates for later prevention and treatment studies. The proposed study will build on an ongoing longitudinal study (PI- Dr. Helen Vlassara- Director of the Division of Diabetes and Aging, Department of Geriatrics, at Mount Sinai School of Medicine) examining the age-dependent relationships among circulating AGE and (dietary) AGE intake, markers of oxidative stress, inflammatory markers, and vascular dysfunction in subjects over the age of 60. In the proposed study, subjects will be cognitively assessed by the Clinical Dementia Rating scale, MMSE and the extensive neuropsychological battery of the Alzheimer's Disease Research Center (ADRC) at Mount Sinai, and evaluated by the ADRC consensus diagnostic conference, both at baseline and at follow up. In addition, at baseline, we will collect DNA for APOE and future genetic studies. Findings from this study may identify AGEs as a new modifiable environmental risk factor, acting together with endogenous mechanisms, negatively affecting cognition. This naturalistic cross-sectional and longitudinal study holds the potential to support future interventions to reduce the impact of AGEs, to prevent or delay cognitive decline in the elderly who are at increasing risk of dementia and AD. Hypotheses: 1- Main hypothesis: Subjects with higher levels of AGEs will show poorer cognitive functioning at baseline. 2- Exploratory hypothesis: Subjects with higher baseline AGEs or larger increases in AGEs over time will show a greater degree of cognitive decline. 3- Exploratory hypothesis: APOE4 will intensify the hypothesized relationships in Hypothesis 1.