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

> **NIH AG R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2026 · $377,253

## Abstract

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
(flutemeta

## Key facts

- **NIH application ID:** 11508145
- **Project number:** 3R01AG080769-02S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Esther Marian Blessing; Juan  Fortea
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AG
- **Fiscal year:** 2026
- **Award amount:** $377,253
- **Award type:** 3
- **Project period:** 2023-02-01T00:00:00 → 2028-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11508145

## Citation

> US National Institutes of Health, RePORTER application 11508145, Sleep and Temperature Disturbance as risk factors for Alzheimer's Disease in Down Syndrome: a Longitudinal Study (3R01AG080769-02S1). Retrieved via AI Analytics 2026-05-20 from https://api.ai-analytics.org/grant/nih/11508145. Licensed CC0.

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