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Establishing a Brain Health Index

Award Number: RF1NS120947
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/07/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Establishing a Brain Health Index - Project Abstract: Polysomnographic Biomarkers of Brain Aging Although cognitive decline is a “normal” part of aging, some individuals clearly age better than others. However, the concept of differential aging has been minimally studied for the brain. Electroencephalogram (EEG) oscillations signals carry rich information regarding brain health and brain aging. Alzheimer’s disease (AD) is associated with fragmented sleep and altered sleep oscillations. Clearance of cerebral beta amyloid through the brain's glymphatic drainage system occurs mainly in non-rapid eye movement (NREM) sleep, and depends on EEG slow oscillations. Cortical generators of sleep EEG oscillations overlap with regions of cortical thinning and loss of functional connectivity in AD. Disturbances of NREM disrupt memory consolidation. Finally, deficient REM sleep contributes to dementia. These observations suggest that brain health may be measurable from information contained in the sleep EEG. In preliminary work we have developed EEG-brain age – a machine learning model that predicts a patient’s age based on patterns of overnight sleeping EEG oscillations. This allows prediction of age with a precision of +/- 7 years. Our preliminary data suggest diabetes and hypertension, chronic HIV infection, an MCI or AD are reflected in the EEG as excessive brain age, and that excessive brain age is independently associated with reduced life expectancy. Our central hypothesis is that sleep physiology data can provide sensitive and specific biomarkers of brain health. This hypothesis is based on our prior work showing that BAI is elevated in several clinical populations. BAI can be accurately calculated using frontal EEG signals, making it suitable for implementation on at-home EEG devices. The rationale for the proposed research is that validating sleep EEG-derived biomarkers as measures of brain health at the level of individual patients would lay the ground for use in clinical trials and patient care. We plan to accomplish the central objective by pursuing two complementary aims. In Aim 1, we will take a hypothesis-driven approach, and test for associations of specific sleep features with specific cognitive deficits and specific structural pathology. In Aim 2, we will take ad data-driven approach, and develop optimized biomarkers of brain health using a novel form of machine learning known as multitask learning, which combine multiple features of sleep – including conventional features, as well as data-driven features directly learned from the data – to predict or “explain” variation in cognitive performance and in structural brain MRI measures that are indicative of brain health or disease. The project will take advantage of a large and diverse set of sleep data (>33,000 patients), as well as thousands of brain MRI an cognitive testing results. At the conclusion of this study, we expect to have a better understanding of the role sleep oscillations play in brain health, and clinically useful brain health biomarkers. These outcomes will aid development of interventions to promote brain health.


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 = -$161,751 )
2025	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	10/11/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$161,751
2025	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/20/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = -$161,751

Issue Date FY: 2024 ( Subtotal = -$232,555 )
2024	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/9/2024	NEW	-$232,555
														Subtotal = -$232,555

Issue Date FY: 2023 ( Subtotal = -$125,443 )
2023	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/7/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$862,803
2023	2021	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/6/2023	NEW	-$988,246
														Subtotal = -$125,443

Issue Date FY: 2021 ( Subtotal = $2,494,802 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/28/2021	NEW	$2,494,802
														Subtotal = $2,494,802

Grand Total All Awards = $1,975,054

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Establishing a Brain Health Index

Award Number: RF1NS120947

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/07/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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