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Multi-Domain Sensory Measures as Biomarkers of Alzheimer's Disease in Preclinical and Prodromal Stages

Award Number: R01AG061788
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Multi-Domain Sensory Measures as Biomarkers of Alzheimer's Disease in Preclinical and Prodromal Stages - PROJECT ABSTRACT Sensitive, practical, and non-invasive methods to identify Alzheimer’s disease (AD) in preclinical and prodromal stages are desperately needed to improve patient care by identifying those to target with therapeutic and/or lifestyle interventions. Cutting-edge clinical trials of anti-amyloid therapies in amyloid-positive older adults and prodromal AD patients and future trials of anti-tau therapies have the potential to lead to new treatments targeting AD pathophysiology in preclinical stages. Thus, there is a critical need to develop new sensitive and readily accessible biomarkers to detect AD-related pathophysiology before marked clinical decline. Recent data suggest subtle impairments in sensory function, including vision, olfaction, and hearing, may occur with and even precede clinically relevant cognitive decline. Measures of sensory function are ideal screening biomarkers because of their ease of use, non-invasiveness, and low cost. However, changes in sensory function in very early stages of AD have not been comprehensively investigated with respect to novel neuroimaging tools. Further, the combination of sensory measures from multiple domains has not been evaluated in the same participants. These knowledge gaps are an important bottleneck because it prevents the field from using sensory measures to identify individuals who are most likely to benefit from putative therapies for AD. Understanding how previously underappreciated sensory dysfunction informs us about amyloid and tau pathology, neurodegeneration, and brain connectivity in preclinical and prodromal AD will provide integral knowledge about the nature of these early changes, which has great potential to improve patient care by facilitating early intervention for AD. Our central hypothesis is that early changes in sensory function in preclinical and prodromal AD indicate the presence of AD-related neuropathology in the brain and reflect the initial stages of AD-associated cognitive decline. The aims of this project, in response to PAR-18-519: “Sensory and motor changes as predictors of preclinical Alzheimer’s disease,” are to: [1] Test the hypothesis that changes in visual, olfactory, and auditory measures in preclinical and prodromal stages of AD is driven by cerebral amyloid and tau deposition and/or neurodegeneration; [2] Test the hypothesis that altered brain connectivity within sensory networks is associated with measures of multi-sensory function in preclinical and prodromal AD; [3] Determine whether a combination of sensory biomarkers provides a better prediction of cerebral amyloid and tau deposition, neurodegeneration, and changes in connectivity than a single measure alone in preclinical and prodromal AD; [4] Evaluate the ability of cross-sectional and longitudinal sensory measures to predict future decline in cognition, clinical conversion, and brain atrophy rate. Successful completion of these aims has the potential to alter the current concepts and methodologies of early diagnosis, which in turn will support the development of sensory measures as accessible and cost-effective diagnostic markers for use in screening, diagnosis, clinical trials of AD therapies, and ultimately, treatment.


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: 2027 ( Subtotal = $0 )
2027	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	6	10/8/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2026 ( Subtotal = $1 )
2026	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	001	5	3/13/2026	NON-COMPETING CONTINUATION	$1
2026	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	000	5	3/10/2026	NON-COMPETING CONTINUATION	-$116,042
2026	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	003	6	3/30/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2026	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	005	6	9/4/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$116,042
2026	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	004	5	4/7/2026	NON-COMPETING CONTINUATION	$0
2026	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	002	6	3/19/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$116,042
2026	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	006	6	9/4/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$116,042
														Subtotal = $1

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	000	5	12/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $559,549 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	000	5	1/5/2023	NON-COMPETING CONTINUATION	$559,549
														Subtotal = $559,549

Issue Date FY: 2022 ( Subtotal = $600,108 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	000	4	4/28/2022	NON-COMPETING CONTINUATION	$600,108
														Subtotal = $600,108

Issue Date FY: 2021 ( Subtotal = $645,922 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	000	3	12/16/2020	NON-COMPETING CONTINUATION	$581,329
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	001	3	2/10/2021	NON-COMPETING CONTINUATION	$64,593
														Subtotal = $645,922

Issue Date FY: 2020 ( Subtotal = $607,202 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	001	2	1/30/2020	NON-COMPETING CONTINUATION	$60,720
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	000	2	12/5/2019	NON-COMPETING CONTINUATION	$546,482
														Subtotal = $607,202

Issue Date FY: 2019 ( Subtotal = $611,139 )
2019	2019	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	000	1	2/13/2019	NEW	$611,139
														Subtotal = $611,139

Grand Total All Awards = $3,023,921

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Multi-Domain Sensory Measures as Biomarkers of Alzheimer's Disease in Preclinical and Prodromal Stages

Award Number: R01AG061788

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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