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Sleep and Temperature Disturbance as risk factors for Alzheimer's Disease in Down Syndrome: a Longitudinal Study

Award Number: R01AG080769
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Sleep and Temperature Disturbance as risk factors for Alzheimer's Disease in Down Syndrome: a Longitudinal Study - Project Summary Abstract Down syndrome (DS), the most frequent form of intellectual disability of genetic origin, involves a >95% cumulative risk of Alzheimer’s Disease (AD) by the seventh decade. Further, AD is now the most common cause of death in this population as life expectancy in DS individuals has increased. Importantly, while AD in DS individuals has a mean age of onset 20–30 years younger compared to euploid individuals, there is substantial heterogeneity in this age of onset (between 40 and 70 years old), emphasizing the urgent need to identify and treat modifiable causes of AD in DS. Our work in the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) Cohort has established that clinical and Amyloid/Tau/Neurodegeneration (ATN) related biomarker changes in DS have a similar temporal profile to that in sporadic and autosomal dominant AD, meaning these biomarkers may be used to identify modifiable causes of AD in DS individuals prior to AD dementia onset. Existing literature and our preliminary data suggest that potential causes of AD in euploid individuals, namely age-related sleep and body temperature (Tb) circadian rhythm disturbance, are more severely perturbed in DS compared to euploid older adults: specifically, results suggest that greater obstructive sleep apnea (OSA) severity and lower Tb are particularly important modifiable AD risk factors in DS. This project will test the hypotheses that greater baseline OSA severity and lower baseline Tb will longitudinally predict ATN AD biomarker increase and cognitive decline in initially cognitively stable DS adults. We will recruit 60 DS adults with normal cognition aged 40–60 years old and follow them longitudinally at three annual timepoints over 2 years. Baseline assessments will include screening; cognitive evaluation; at home and in lab polysomnographic assessments overlapping with 36 hours of telemetrically measured Tb data collection, and collection of ATN biomarkers including amyloid (flutemetamol PET SUVR, plasma Aβ), tau (PI-2620 PET SUVR, plasma T-tau and P-tau181) and neurodegeneration (hippocampal volume, cortical thickness, plasma neurofilament light) related biomarkers. Follow-up cognitive evaluations and collection of plasma-based biomarkers will occur annually at all three timepoints, and neuroimaging-based biomarkers at two timepoints (baseline and 2 years). The goals of this study are to test 1) Whether greater baseline OSA apnea hypopnea index (AHI3A) is associated with ATN biomarker severity (Aim 1), 2) Whether lower baseline Tb is associated with greater tau biomarker severity (Aim 2), and 3) Whether OSA severity and lower Tb longitudinally predict greater estimated rate of change in AD biomarkers (Aim 3). Predictors of cognitive decline and additional sleep and Tb parameters will be explored. This novel proposal will advance our understanding of how age-related sleep and thermoregulatory disturbances impact AD biomarker progression in people with DS—a population at high risk for all three AD, OSA, and temperature dysregulation—with the aim of identifying modifiable risk factors in both DS and euploid individuals.


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 = $617,151 )
2026	2026	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Aging Research	000	2	3/20/2026	EXTENSION WITH OR WITHOUT FUNDS	$239,898
2026	2026	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Aging Research	001	2	4/17/2026	SUPPLEMENT FOR EXPANSION	$377,253
														Subtotal = $617,151

Grand Total All Awards = $617,151

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Sleep and Temperature Disturbance as risk factors for Alzheimer's Disease in Down Syndrome: a Longitudinal Study

Award Number: R01AG080769

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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