EFFECTS OF GLYCOXIDATION ON COGNITION

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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.