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Early Biomarkers of Alzheimer's Disease: Using Speech Markers to Detect Mild Cognitive Impairment

Award Number: K23DC019179
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Early Biomarkers of Alzheimer's Disease: Using Speech Markers to Detect Mild Cognitive Impairment - PROJECT SUMMARY Detecting early signs of Alzheimer’s Disease (AD) and mild cognitive impairment (MCI) during the prodromal stage of AD is becoming increasingly important for cost-effective clinical trials, developing targeted intervention strategies, and gaining maximum benefit from currently available treatment plans. However, because of substantial differences in the manifestation of cognitive impairment, preclinical cognitive changes are not discernible from age-related cognitive decline. Although a combined approach of using neuropsychological, fluid, and imaging biomarkers has relatively improved the timely diagnosis of AD, measurement of these biomarkers is expensive and highly technology-dependent, making these techniques impractical for use in many older adults across different settings. In addition, assessment of cognitive functions through the use of neuropsychological batteries remains the gold-standard in clinical trials and evaluation of intervention efficacy. Thus, it is critical to identify early detectors that are 1) sensitive to pathologies of AD, 2) strongly predictive of future change in cognition, and 3) accessible and feasible across diverse settings. Based on our recent findings, which have identified measures of speech motor control as a powerful aid in indexing early stages of neurodegenerative diseases such as amyotrophic lateral sclerosis and primary progressive aphasia, we propose assessment of speech markers as an alternative or complementary and ecologically valid strategy for identifying adults at risk of developing cognitive impairment due to AD. Speech production is one of humans’ most complex motor behaviors, as it relies on tight integration of cognition, sensory, and motor processes which are all subject to change with advancing age. We hypothesize that the rate of age-related changes in speech motor control of adults can be influenced by genetic susceptibility to develop AD. In addition, we hypothesize that measures of speech elicited during cognitively-demanding speech tasks can differentiate carriers of APOE ε4 (i.e., the major gene known to increase AD risk) from noncarriers and that baseline speech acoustic and kinematic measures can predict later cognitive decline. The proposed research will innovatively use acoustics and articulatory kinematics in combination with neuroimaging to pursue three Aims. In Aim 1, we will determine the effect of aging on speech motor control of adults with APOE ε4 positive (ε4+) and APOE ε4 negative (ε4-) genotypes matched in sex and education. In Aim 2, we will identify the brain structural and resting-state functional bases for age- related changes in speech measures of adults with ε4+ and ε4- genotypes. Finally, in Aim 3, we will determine 1) whether baseline speech acoustic/ kinematic measures predict cognitive change over two years, as quantified by Hopkins Learning Test-Revised (HVLT-R) and Trail Making Test (TMT) scores; and 2) if speech and cognitive changes are mediated through alterations in brain structure and function. The findings of this study will provide critical information about measures of speech motor control that can be efficiently incorporated into neuropsychological testing to optimize the clinical assessment of AD.


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 = $0 )
2026	2025	THE MGH INSTITUTE OF HEALTH PROFESSIONS, INC.	36 1ST AVE	CHARLESTOWN	MA	02129	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	5	5/19/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $197,127 )
2025	2025	THE MGH INSTITUTE OF HEALTH PROFESSIONS, INC.	36 1ST AVE	CHARLESTOWN	MA	02129	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	5	7/25/2025	NON-COMPETING CONTINUATION	$197,127
														Subtotal = $197,127

Issue Date FY: 2024 ( Subtotal = $197,127 )
2024	2024	THE MGH INSTITUTE OF HEALTH PROFESSIONS, INC.	36 1ST AVE	CHARLESTOWN	MA	02129	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	4	8/8/2024	NON-COMPETING CONTINUATION	$197,127
														Subtotal = $197,127

Issue Date FY: 2023 ( Subtotal = $273,047 )
2023	2023	MGH INSTITUTE OF HEALTH PROFESSIONS, INC.THE	36 1ST AVE	BOSTON	MA	02129	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	3	7/20/2023	NON-COMPETING CONTINUATION	$197,447
2023	2023	MGH INSTITUTE OF HEALTH PROFESSIONS, INC.THE	36 1ST AVE	BOSTON	MA	02129	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	3	8/11/2023	SUPPLEMENT FOR EXPANSION	$75,600
														Subtotal = $273,047

Issue Date FY: 2022 ( Subtotal = $252,827 )
2022	2022	MGH INSTITUTE OF HEALTH PROFESSIONS, INC.THE	36 1ST AVE	BOSTON	MA	02129	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	2	8/22/2022	SUPPLEMENT FOR EXPANSION	$54,000
2022	2022	MGH INSTITUTE OF HEALTH PROFESSIONS, INC.THE	36 1ST AVE	BOSTON	MA	02129	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	2	7/26/2022	NON-COMPETING CONTINUATION	$198,827
														Subtotal = $252,827

Issue Date FY: 2021 ( Subtotal = $199,475 )
2021	2021	MGH INSTITUTE OF HEALTH PROFESSIONS, INC.THE	36 1ST AVE	BOSTON	MA	02129	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	1	7/27/2021	NEW	$199,475
														Subtotal = $199,475

Grand Total All Awards = $1,119,603

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Early Biomarkers of Alzheimer's Disease: Using Speech Markers to Detect Mild Cognitive Impairment

Award Number: K23DC019179

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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