Alzheimer's Disease Research
Kristine Yaffe, M.D.
University of California, San Francisco
San Francisco, CA
Title: Glucose Regulation, Cognitive & Brain Changes in Elders
Non-Technical Title: The Effects of Diabetes and Markers of Glucose Control on Cognitive Aging
Acknowledgements: This grant is made possible due to a generous bequest from the Estate of Frederick J. Pelda.
Duration: April 1, 2010 - November 30, 2014
Award Type: Standard
Award Amount: $394,755
By conducting our study aims, we will greatly advance our understanding of how diabetes and glucose regulation affect cognitive and brain aging. In addition, we will investigate several possible mechanisms linking diabetes to cognitive impairment. In so doing, we hope to identify strategies for prevention of cognitive decline among those with and at risk for diabetes.
A. Big Picture: We are in the midst of two important converging demographic shifts in this country. One is the "graying" of America and the exponential expansion of the elderly population and the other is the rapid growth of obesity and diabetes in this country, due to changes in our lifestyle. There is good evidence that diabetes increases ones risk for developing dementia but we do not know much about the mechanisms for this and if those with more mild forms of diabetes or abnormal glucose control are also at increased risk for cognitive impairment. We will undertake a series of scientific aims that will greatly improve our understanding of how diabetes may affect the aging brain.
B. Benefits to public and research field: If we establish these links between diabetes and cognitive aging, it will offer possible ways to prevent cognitive impairment. For example, elderly diabetes may need to be screened and treated for cognitive deficits and those at risk for diabetes could be monitored more closely for cognitive symptoms.
C. Approach: We will accomplish these aims as part of an ongoing study of aging involving nearly 3,000 elders in which participants have had repeated measures of cognitive function gathered over 11 years of follow-up. In addition, state of the art assays of glucose regulation have been collected. Thus, we will, in a very cost-effective manner, be able to investigate the important relationships between diabetes, diabetes control, glucose regulation in non-diabetics and cognitive function in older adults. Furthermore, we will explore how these metabolic parameters are associated with structural brain changes in a subset of participants.
D. Why innovative and unique: This work is innovative in that we are linking several important blood markers of diabetes and glucose regulation with cognition and brain MRI changes. In addition, we will explore several ways in which diabetes may cause detrimental changes in the brain.
E. Interest in field: I am particularly interested in trying to prevent cognitive impairment in older adults. Diabetes has emerged as a fascinating and common disease that has a big effect on cognition but we still do not understand some of the ways these conditions are linked. I hope that by conducting this research, we will improve our understanding of cognitive impairment and importantly, suggest ways to prevent or mitigate against cognitive impairment.
Yaffe, K, Lindquist K, Schwartz A, Vitartas C, Vittinghoff E, Satterfield S, Simonsick E, Launer L, Rosano C, Cauley J, Harris T for the Health ABC Study. Advanced Glycation Endproduct Level and Accelerated Cognitive Aging: Findings from the Health ABC Study. Neurology. 77(14) 1351-6.
Falvey, C, Rosano, C, Simonsick, E, Harris, T, Strotmeyer, E, Satterfiled, S, Yaffe, K. Macro and micro-structural MRI changes associated with diabetes in non-demented older adults.
Yaffe K, Falvey CM, Hamilton N, Schwartz AV, Simonsick EM, Satterfield S, Cauley J, Rosano R, Launer L, Strotmeyer ES, Harris T. Diabetes, Glucose Control, and 9-Year Cognitive Decline Among Older Adults Without Dementia. Archives of Neurology. 2012; 69(9): 1170-1175.
Yaffe K, Falvey CM, Hamilton N, Harris TB, Simonsick EM, Strotmeyer ES, Shorr RI, Metti A, Schwartz AV for the Health ABC Study. The association between hypoglycemia and dementia in a biracial cohort of older adults. JAMA Intern Med
In the U.S., nearly 26 million adults have diabetes and many studies show that elders with diabetes may have a greater risk of cognitive decline (reduced mental function) and Alzheimer disease (AD). Therefore, Dr. Yaffe and colleagues seek to clarify how diabetes may be related to reduced cognitive function. They have completed analysis on three of the four aims in their project and another aim is underway. Results from aim 2 have been published in the journal Neurology, and results from aim 1 and 4 have been or are about to be submitted to a high-impact journals.
Results from the study showed that participants without dementia but with diabetes had worse baseline cognitive test scores and greater decline in test scores over 9 years, as compared to participants with normal glucose or recently diagnosed diabetes. They also found that those with higher circulating levels of pentosidine—a type of advanced glycation endproduct (AGE)—had worse baseline cognitive function and greater decline over 9 years than those with lower levels. AGEs are the end result from reactions between glucose (sugars) and proteins that have been implicated in many age- and diabetes-related conditions. Few studies have investigated circulating AGEs as a biomarker for cognition in humans. Results from Dr. Yaffe’s MRI analysis have shown that participants with diabetes have underlying changes in brain structure that may indicate increased risk of cognitive decline.
These results are important as they strongly support the evidence that diabetes accelerates cognitive decline, and this may help explain why elders with diabetes have greater risk of AD. The next steps will be to investigate exactly why diabetes accelerates cognitive decline. Hopefully, information learned will guide strategies to prevent the increased risk of cognitive impairment among elderly individuals with diabetes.