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The effect of physical activity on cognition relative to APOE genotype (PAAD-II)

Award Number: R01AG058919
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2018
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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The effect of physical activity on cognition relative to APOE genotype (PAAD-II) - Project Summary: By 2050, the prevalence of Alzheimer’s disease (AD) in the United States is predicted to reach 13.8 million. Despite worldwide research efforts, a cure for AD has not been identified. Thus, it is critical to identify preventive strategies that can reduce the risk of or delay the onset of AD. Physical activity (PA) has potential in this regard. Meta-analytic reviews and our own experimental studies show that older adults who participate in PA experience larger gains in cognitive performance than do controls. Prospective studies also show that PA is associated with a lower risk of AD and that the relationship between baseline PA and subsequent cognitive performance is moderated by a susceptibility gene for AD (apolipoprotein, APOE). In a Phase I proof-of-concept trial, we showed that individuals with a family history of AD (FH+) achieve cognitive benefits in association with PA and that these benefits were even evident in those with a genetic risk for AD (i.e., APOE e4 carriers, APOE4+). However, no published randomized controlled trial has assessed the effects of PA on cognition in cognitively normal FH+ individuals relative to APOE4 status. In addition, in currently funded trials beginning to address this gap, the focus is on older adults (65+); thus limiting the ability to identify protective effects that may be more evident with earlier interventions. Lastly, current evidence does not elucidate mechanisms to explain how PA benefits cognitive performance. These gaps in the literature have motivated our Phase II trial, in which we extend our past work by proposing a randomized clinical trial to: (a) test the causal link between PA and cognitive performance in middle-aged adults (40-65 years) with a FH+, and (b) determine if the effect is moderated by APOE4 carrier status. We will collect neuroimaging measures of cerebral structure, white matter integrity, and resting state connectivity; assess putative biological markers; and (using moderated mediation analyses) increase understanding of underlying mechanisms and of the extent to which effects are moderated by APOE4 carrier status. To test our hypotheses, we will randomly assign 240 cognitively normal, middle-aged adults to a 1-year PA program or a usual care control. We will assess cognitive performance at pre-, mid-, and post-test, and obtain MRI scans and blood samples at pre- and post- test. We will examine the effects of PA on cognitive performance and on neurological and biological mechanisms and will explore the moderating role of APOE4. A strength of this study is that we incorporate cognitive measures and MRI sequences used in a Phase III clinical trial (1R01AG053952) testing the effects of PA on cognition in older adults (65-80 years), and we are collaborating with the PI of that trial (Erickson). This will allow us to leverage NIH’s resources by compiling data across a broad age range. Importantly, findings from this study may support PA as a means of improving cognitive performance by those with a heightened risk for AD. This could have public health implications, because delaying AD by 1 year could reduce its incidence by 11%.


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: 2026 ( Subtotal = -$47,392 )
2026	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN ST	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	000	5	11/25/2025	NON-COMPETING CONTINUATION	-$47,392
														Subtotal = -$47,392

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN ST	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	000	5	3/11/2024	NON-COMPETING CONTINUATION	$0
2024	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN ST	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	001	5	3/12/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $686,652 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	000	5	4/15/2022	NON-COMPETING CONTINUATION	$660,462
2022	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	001	5	4/19/2022	SUPPLEMENT FOR EXPANSION	$26,190
														Subtotal = $686,652

Issue Date FY: 2021 ( Subtotal = $745,717 )
2021	2021	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	000	4	3/29/2021	NON-COMPETING CONTINUATION	$745,717
														Subtotal = $745,717

Issue Date FY: 2020 ( Subtotal = $736,447 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	000	3	3/5/2020	NON-COMPETING CONTINUATION	$699,781
2020	2020	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	001	3	8/10/2020	SUPPLEMENT FOR EXPANSION	$36,666
														Subtotal = $736,447

Issue Date FY: 2019 ( Subtotal = $706,528 )
2019	2019	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	001	2	3/15/2019	NON-COMPETING CONTINUATION	$706,528
2019	2018	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	000	1	12/19/2018	NEW	$0
														Subtotal = $706,528

Issue Date FY: 2018 ( Subtotal = $730,680 )
2018	2018	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Aging Research	000	1	7/20/2018	NEW	$730,680
														Subtotal = $730,680

Grand Total All Awards = $3,558,632

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The effect of physical activity on cognition relative to APOE genotype (PAAD-II)

Award Number: R01AG058919

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2018

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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