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Acute exercise and the cerebral metabolic response in aging and Alzheimer's Disease

Award Number: R01AG062548
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Acute exercise and the cerebral metabolic response in aging and Alzheimer's Disease - ABSTRACT / PROJECT SUMMARY There is evidence that physical activity and exercise benefit the brain, but the mechanisms for this benefit are unclear. The chronic benefits of exercise are likely a product of discreet, acute responses in exercise-related blood biomarkers and brain metabolism. This acute exercise response has not been compared in aging and Alzheimer’s Disease (AD). It is known that acute exercise elicits a powerful peripheral response in young cohorts, and exercise-related biomarkers such as glucose and lactate readily penetrate the brain. Thus, studies of these effects in aged and AD individuals are needed. It is critical to characterize and understand the acute effects of exercise, including different exercise intensities, in terms of the peripheral metabolic response and relationship with brain metabolism. This will help determine potential mechanisms for brain benefits of exercise and better inform the design of future clinical trials. Our primary goal is to characterize the acute exercise response of brain glucose metabolism and exercise-related blood biomarkers. We will characterize the brain metabolic response to an acute bout of moderate and higher intensity exercise and characterize the extent to which this differs between nondemented (ND) elderly and AD individuals. Related to this primary goal, we will quantify the peripheral biomarker response to moderate and higher intensity exercise and how this relates to brain metabolic change in both groups. We will implore a rigorous experimental design, with tightly controlled timings. We will generate a timecourse of blood draws prior to, during, and following exercise in ND and AD subjects to explore disease-related differences. We will focus on a specific exercise biomarker, lactate, but we will also characterize a wider panel of exercise-related biomarkers. We will expand on our exercise studies by leveraging a lactate clamp procedure, where we can characterize differences in lactate uptake and use (turnover) between diagnosis groups. By using stable isotopes, the lactate clamp will allow us to simultaneously examine complex dynamics of energy metabolism, such as lactate appearance, disappearance, and oxidation, and evaluate if AD subjects use this key metabolite differently. It also allows characterization of acute effects of lactate on cognition in the absence of other exercise effects. Taken together, these studies will allow us to elucidate the relationship between quantifiable blood biomarkers and brain acute response to exercise, and how exercise intensity may be important. Through in-depth characterization of these physiological responses in aging and AD, we will obtain important information regarding how relatively non-invasive outcomes, such as heart rate and blood biomarker response, relate to a key brain outcome measure (cerebral glucose metabolism). By characterizing thresholds for response of biomarkers that are needed to elicit acute brain changes, this could provide insight for the design of future long-term exercise intervention studies that are most likely to benefit the brain (i.e. moderate vs. higher intensity exercise, characteristics of participants who respond, etc) to maximize target engagement.


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: 2024 ( Subtotal = $480,104 )
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Aging Research	000	5	2/1/2024	NON-COMPETING CONTINUATION	$432,094
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Aging Research	001	5	6/10/2024	NON-COMPETING CONTINUATION	$48,010
														Subtotal = $480,104

Issue Date FY: 2023 ( Subtotal = $487,124 )
2023	2023	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Aging Research	000	4	3/2/2023	NON-COMPETING CONTINUATION	$487,124
														Subtotal = $487,124

Issue Date FY: 2022 ( Subtotal = $487,124 )
2022	2022	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Aging Research	001	3	6/8/2022	NON-COMPETING CONTINUATION	$48,712
2022	2022	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Aging Research	000	3	1/14/2022	NON-COMPETING CONTINUATION	$438,412
														Subtotal = $487,124

Issue Date FY: 2021 ( Subtotal = $453,447 )
2021	2021	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Aging Research	000	2	1/29/2021	NON-COMPETING CONTINUATION	$453,447
														Subtotal = $453,447

Issue Date FY: 2020 ( Subtotal = $476,043 )
2020	2020	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Aging Research	001	1	6/25/2020	NEW	$0
2020	2020	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Aging Research	000	1	2/5/2020	NEW	$476,043
														Subtotal = $476,043

Grand Total All Awards = $2,383,842

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Acute exercise and the cerebral metabolic response in aging and Alzheimer's Disease

Award Number: R01AG062548

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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