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Glucose homeostasis and the risk of Alzheimer's disease and Alzheimer's disease related dementias in the Multi-Ethnic Study of Atherosclerosis

Award Number: R01AG070881
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Glucose homeostasis and the risk of Alzheimer's disease and Alzheimer's disease related dementias in the Multi-Ethnic Study of Atherosclerosis - PROJECT SUMMARY Alzheimer’s disease and Alzheimer’s disease related dementias pose an enormous public health challenge. In the absence of a cure, prevention or delay of pathology offers the most promising avenue to control the disease. Despite growing recognition that cardiometabolic risk factors are major contributors to cognitive decline, Alzheimer’s disease, and Alzheimer’s disease related dementias, many gaps remain in our understanding of the mechanisms and pathways between glucose homeostasis and cognitive function. While type 2 diabetes (T2D) is increasingly recognized as a major preventable risk factor for Alzheimer’s disease and related dementias, intensive glucose control in T2D has not been shown to prevent cognitive decline in trials. This finding and inconsistent results for the influence of glucose control (HbA1c) on cognitive decline pose the question: What aspects of dysglycemia, and its inverse glucose homeostasis, increase the risk of Alzheimer’s disease or related dementias? This study’s overall goal is to investigate the role of dysglycemia across the glucose spectrum on incident neurocognitive markers of Alzheimer’s disease and Alzheimer’s disease related dementias in a multi-ethnic cohort: The Multi-Ethnic Study of Atherosclerosis (MESA). MESA enrolled 6814 men and women beginning in 2000. MESA participants have been extensively studied with respect to cardiovascular risk factors and outcomes and MESA-MIND, a cognitive ancillary, adds comprehensive cognitive testing and neuroimaging including brain MRI and amyloid β PET scans. MESA has a 7th exam occurring between 2021-2023 that will be concordant with the second MESA-MIND visit. While fasting glucose was obtained at every exam, and HbA1C and HOMA-IR measured at some exams, continuous glucose has not been measured. Adding continuous glucose monitoring wearable technology to MESA Exam 7 and repeated two years later provides a unique and timely opportunity to answer challenging questions about the role of dysglycemia that continue to impede the development of successful prevention strategies for Alzheimer’s disease and Alzheimer’s disease related dementias. This study will also add new measurements of insulin resistance (HOMA-IR). This ancillary to MESA will 1) Investigate the antecedent determinants of glucose homeostasis (from continuous glucose monitors at Exam 7 (n=2000) and change over two years (n=1000), 2. Determine whether continuous glucose markers of glucose homeostasis, dysglycemia, and change over time are associated with incident neurocognitive indicators of Alzheimer’s disease or Alzheimer’s disease related dementias (n=2000), and 3. Investigate the contributions of dysglycemia to Alzheimer’s disease and related dementia pathologies by sex and race/ethnicity (n=2000). Findings from this research will identify new mechanisms for the development of Alzheimer’s disease and Alzheimer’s disease related dementias, discover new primary and secondary prevention targets, and have the potential to change clinical care.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $374,952 )
2025	2024	MEDSTAR HEALTH RESEARCH INSTITUTE INC.	10980 GRANTCHESTER WAY 7TH FL	COLUMBIA	MD	21044	HOWARD	USA	Aging Research	002	3	3/28/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$724,004
2025	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	2	3/27/2025	EXTENSION WITH OR WITHOUT FUNDS	-$724,004
2025	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	2	3/25/2025	EXTENSION WITH OR WITHOUT FUNDS	$374,952
														Subtotal = $374,952

Issue Date FY: 2024 ( Subtotal = $724,004 )
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	2	7/30/2024	EXTENSION WITH OR WITHOUT FUNDS	$724,004
														Subtotal = $724,004

Grand Total All Awards = $1,098,956

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Glucose homeostasis and the risk of Alzheimer's disease and Alzheimer's disease related dementias in the Multi-Ethnic Study of Atherosclerosis

Award Number: R01AG070881

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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