Saturday, June 28, 2025 6/28/2025

Cognitive challenge to reveal systemic neurophysiology biomarkers in pre-symptomatic Alzheimer’s disease

Award Number: R01AG063857
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2026

Group Awards By:

View Award Description

Cognitive challenge to reveal systemic neurophysiology biomarkers in pre-symptomatic Alzheimer’s disease - The burden on Alzheimer’s disease (AD) is growing due to longer life span and lack of effective treatment. The knowledge gap exists for early detection and prediction of symptom onset. AD pathology (amyloid/tau) and synaptic dysfunction precedes symptoms by decades and offers a window of opportunity for early AD detection. Current early AD diagnosis depends on expensive imaging or invasive cerebrospinal fluid (CSF) detection of amyloid/tau. Our goal is to identify non-invasive biomarkers that fill this gap with simple tests benchmarked to amyloid/tau biomarkers. Our early studies defined pre-symptomatic AD: elderly study participants were classified as cognitively healthy (CH) in a multi-domain, neuropsychometric battery. We classify CH participants into two groups based on a regression-derived CSF Aß42/Tau ratio cutoff: CH individuals with pathological ratio (CH-PAT) or with normal ratio (CH-NAT). After 4 years, 40% of CH-PAT but no CH-NAT individuals declined cognitively, providing a strong cohort to evaluate biomarkers for pre- symptomatic AD (CH-PATs) from normal aging (CH-NATs). AD affects multiple nervous systems. Tightly related to our health, the interactions between conscious executive function, subliminal processing, and autonomic regulation (CSA system) respond to internal and external stimuli with neural oscillations that are affected by synaptic dysfunctions. The CSA neural oscillations can be detected by non-invasive electrophysiological methods: EEG and ECG, benchmarked to amyloid/tau. Individual CSA dysfunctions have been reported in the mild cognitive impairment stage, while CSA has not been studied in the pre-symptomatic AD. We hypothesized that CSA system measurements combine to provide robust biomarkers for pre-symptomatic AD. Analogous to the stress test to unmask coronary insufficiency, our cognitive challenge revealed CH-PATs had frontal hyper-activities with low load challenge and insufficient cognitive resources with high load challenges, hyperresponsivity to subliminal interference, and hyperactive autonomic regulation. Further, combined CSA biomarkers improve detection of pre-symptomatic AD. Therefore, we hypothesize that neural oscillations during cognitive challenge will reveal altered executive functions in pre-symptomatic AD, correlate with compromised subliminal processing and autonomic nervous function, and their combination will improve detection and prediction of pre-symptomatic AD. Our Specific Aims will test our hypothesis in a new cohort and test the ability of CSA biomarkers to identify CH- PATs and predict decline in a 2-year longitudinal study. Accomplishing this CSA approach will provide multiple novel translational biomarkers to characterize pre-symptomatic AD. These biomarkers are non-invasive, benchmarked to established CSF biomarkers. Our research addresses an important gap in pre-symptomatic AD detection and prediction of AD symptom onset.


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 = $829,499 )
2025	2025	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	001	5	3/31/2025	NON-COMPETING CONTINUATION	$726,974
2025	2025	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	002	5	6/10/2025	NON-COMPETING CONTINUATION	$64,618
2025	2024	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	000	4	3/28/2025	NON-COMPETING CONTINUATION	$37,907
														Subtotal = $829,499

Issue Date FY: 2024 ( Subtotal = $731,933 )
2024	2024	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	000	4	2/8/2024	NON-COMPETING CONTINUATION	$658,741
2024	2024	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	001	4	7/3/2024	NON-COMPETING CONTINUATION	$73,192
														Subtotal = $731,933

Issue Date FY: 2023 ( Subtotal = $731,933 )
2023	2023	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	000	3	3/9/2023	NON-COMPETING CONTINUATION	$731,933
														Subtotal = $731,933

Issue Date FY: 2022 ( Subtotal = $731,933 )
2022	2022	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	001	2	6/13/2022	NON-COMPETING CONTINUATION	$73,195
2022	2022	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	000	2	2/15/2022	NON-COMPETING CONTINUATION	$658,738
														Subtotal = $731,933

Issue Date FY: 2021 ( Subtotal = $771,566 )
2021	2021	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	002	1	9/7/2021	NEW	$13,499
2021	2021	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	001	1	7/15/2021	NEW	$0
2021	2021	HUNTINGTON MEDICAL RESEARCH INSTITUTES	686 S FAIR OAKS AVE	PASADENA	CA	91105	LOS ANGELES	USA	Aging Research	000	1	5/10/2021	NEW	$758,067
														Subtotal = $771,566

Grand Total All Awards = $3,796,864

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Cognitive challenge to reveal systemic neurophysiology biomarkers in pre-symptomatic Alzheimer’s disease

Award Number: R01AG063857

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer