Saturday, October 18, 2025 10/18/2025

Look AHEAD Sleep: Sleep-disordered breathing, circadian rest/activity rhythms, and the risk of Alzheimer's disease and related dementias in Look AHEAD

Award Number: R01AG074562
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Look AHEAD Sleep: Sleep-disordered breathing, circadian rest/activity rhythms, and the risk of Alzheimer's disease and related dementias in Look AHEAD - Project Summary Sleep disordered breathing (SDB) and altered circadian rest/activity rhythms (CRARs) are increasingly recognized as risk factors for Alzheimer’s disease and related dementias. Obesity and type 2 diabetes (T2D) are leading lifestyle risk factors for poor cognitive outcomes, and are closely linked to SDB and circadian alterations. The roles of SDB and altered CRARs in the promotion of cognitive decline and dementia risk, however, have not been well studied in older overweight or obese individuals with T2D, who are already vulnerable to cognitive decline. The proposed ancillary investigation to the Look AHEAD Study will quantify SDB and CRARs (through home sleep testing and wrist actigraphy) and will use a validated telephone cognitive assessment protocol in 1,500 Look AHEAD participants, to evaluate the links of SDB and altered CRARs with cognitive decline and adjudicated clinical conditions: mild cognitive impairment, Alzheimer’s disease, and Alzheimer’s disease related disorders, in this cohort. We will investigate ~20-year diabetes control and weight trajectories, and APOE ε4 carrier status as potential effect modifiers, and explore blood based biomarkers of Alzheimer’s disease (Aβ42/Aβ40, total tau, pTau181, and NfL). Finally, we will leverage Look AHEAD’s randomized controlled trial design to examine whether participants who were randomized to an intensive lifestyle intervention (ILI) that targeted diet and physical activity (vs. a diabetes support and education (DSE) control condition) exhibit lower rates of SDB and more robust, less phase-delayed CRARs in later life. We will determine whether differences in these SDB/circadian characteristics are associated with maintenance of cognitive function in older adulthood. Results of this study—conducted by a team of investigators with expertise in aging, sleep, diabetes, and cognitive decline and Alzheimer’s disease—will advance our understanding of how SDB and altered CRARs affect brain health among older adults with T2D and overweight/obesity, and whether a lifestyle intervention produces durable effects on sleep/circadian health that translate into sustained brain health in this at-risk population.


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 = $1,616,243 )
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	4	8/26/2025	NON-COMPETING CONTINUATION	$1,616,243
														Subtotal = $1,616,243

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	3	6/13/2024	NON-COMPETING CONTINUATION	$0
2024	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	3	7/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $2,128,281 )
2023	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	3	5/18/2023	NON-COMPETING CONTINUATION	$2,128,281
														Subtotal = $2,128,281

Issue Date FY: 2022 ( Subtotal = $2,143,493 )
2022	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	2	5/31/2022	NON-COMPETING CONTINUATION	$2,143,493
2022	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	1	11/5/2021	NEW	$0
														Subtotal = $2,143,493

Issue Date FY: 2021 ( Subtotal = $1,704,394 )
2021	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	1	8/11/2021	NEW	$1,704,394
2021	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	1	8/18/2021	NEW	$0
														Subtotal = $1,704,394

Grand Total All Awards = $7,592,411

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Look AHEAD Sleep: Sleep-disordered breathing, circadian rest/activity rhythms, and the risk of Alzheimer's disease and related dementias in Look AHEAD

Award Number: R01AG074562

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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