Mount Sinai ADRC: Project 1 (Schimming) | PROJECT SUMMARY Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both common diseases that increase with age. The prevalence of dementia in the elderly is about 14%, accounting for one in seven persons and T2D is estimated to be over 26% in elderly Americans. Many studies have linked T2D to cognitive impairment (CI) and increased risk for AD, but there is significant controversy. The co-occurrences of these diseases are more commonly reported when AD is assessed clinically and when T2D is self reported. Some but not all reports suggest that non-amnestic CI is more prominent in T2D than AD. Pathological studies suggest equal or less amyloid pathology in the presence of T2D for comparable clinical impairment while other studies suggest that insulin resistance is specifically linked to CI and AD. Further, studies seldom consider vascular pathology and inflammatory markers or their interaction with AD markers. Despite these controversies it is clear that clinically, T2D is associated with significant CI which may be progressive and may be exacerbated but AD pathology. The known cognitive deficits of T2D are highly associated with functional disability and there is little evidence that therapeutic control of diabetes improves cognition. Thus, it is critical that we understand the possible interactive pathologies in AD and T2D. To this end, this project describes a plan to comprehensively examine a cohort of elders (over 65) to examine the impact of T2D. Moreover we have proposed to recruit a Latino cohort, as these individuals are at particular risk of both T2D and AD. Clinical and cognitive assessments as well as confirmatory and quantitative evaluation of T2D markers will characterize the populations. CSF markers of amyloid and tau, neuroimaging studies and inflammatory markers will also be conducted in this cohort which will be followed for a minimum of 2 years. With this information we will determine the cognitive and functional profile of T2D and its overlap with the cognitive and functional profile of AD pathology. We will look to confirm a non-amnestic CI signature, possibly unique from AD. We will look at the role of AD and vascular biomarker in defining T2D . We expect that T2D will be associated with vascular and inflammatory measures and A and tau, but the association will be more prominent for vascular and inflammatory measures than for A or tau. Finally we will examine the trajectory of cognitive performance over a minimum of 2 years to determine if T2D is associated with either a global or focal progressive loss of cognition. These studies will form the critical background for future work to understand the cognitive impact of T2D and its relation to AD risk.