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.

Public Health Relevance

Mount Sinai ADRC: Project 1 (Schimming) | NARRATIVE Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both common diseases that increase with age. Both are associated with significant cognitive impairment (CI) and there are many reports of the co-occurrence of the two conditions. Also these conditions are particularly common among Latino elders. This project will engage Latinos over age 65 to examine the underlying biology of CI in the presence of T2D and risks for AD. This is the first step in determining the best approach for developing interventions for the CI associated with these conditions. AD and T2D are responsible for significant healthcare cost at the individual, national and international level and are responsible for significant loss of quality of life for patients and families. This research may provide important information for developing interventions for the CI of these overlapping conditions, thereby addressing a serious public health problem.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005138-34
Application #
9528387
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
34
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Mincer, Joshua S; Baxter, Mark G; McCormick, Patrick J et al. (2018) Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project. Anesth Analg 126:1675-1683
Hadjichrysanthou, Christoforos; McRae-McKee, Kevin; Evans, Stephanie et al. (2018) Potential Factors Associated with Cognitive Improvement of Individuals Diagnosed with Mild Cognitive Impairment or Dementia in Longitudinal Studies. J Alzheimers Dis 66:587-600
Ting, Simon Kang Seng; Foo, Heidi; Chia, Pei Shi et al. (2018) Dyslexic Characteristics of Chinese-Speaking Semantic Variant of Primary Progressive Aphasia. J Neuropsychiatry Clin Neurosci 30:31-37
Hanfelt, John J; Peng, Limin; Goldstein, Felicia C et al. (2018) Latent classes of mild cognitive impairment are associated with clinical outcomes and neuropathology: Analysis of data from the National Alzheimer's Coordinating Center. Neurobiol Dis 117:62-71
Miller, M L; Ren, Y; Szutorisz, H et al. (2018) Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability. Mol Psychiatry 23:1328-1335
Bryois, Julien; Garrett, Melanie E; Song, Lingyun et al. (2018) Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia. Nat Commun 9:3121
Fazio, Leonardo; Pergola, Giulio; Papalino, Marco et al. (2018) Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory. Proc Natl Acad Sci U S A 115:5582-5587
Gusev, Alexander; Mancuso, Nicholas; Won, Hyejung et al. (2018) Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. Nat Genet 50:538-548
Khan, Atlas; Liu, Qian; Wang, Kai (2018) iMEGES: integrated mental-disorder GEnome score by deep neural network for prioritizing the susceptibility genes for mental disorders in personal genomes. BMC Bioinformatics 19:501
Burke, Shanna L; Hu, Tianyan; Fava, Nicole M et al. (2018) Sex differences in the development of mild cognitive impairment and probable Alzheimer's disease as predicted by hippocampal volume or white matter hyperintensities. J Women Aging :1-25

Showing the most recent 10 out of 555 publications