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Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics

Award Number: K23MH129882
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics - PROJECT SUMMARY/ABSTRACT This K23 Career Development Award is designed to provide the conceptual knowledge and technical skills necessary for the PI to pursue a career as an independent investigator evaluating brain network targets to optimize non-pharmacologic interventions for difficult-to-treat mood and cognitive disturbances in aging. Apathy is a persistent and disabling disorder of motivation that afflicts 30-50% of patients with late-life depression (LLD). Apathy worsens clinical outcomes in LLD, as apathetic depressed patients have poor response to existing treatments and higher rates of hospitalization, functional decline, and increased caregiver burden. Functional network abnormalities in a core set of brain circuits that interact to support motivated behavior (salience, executive control, and reward networks) may underlie apathy of LLD. Options for the efficacious treatment of apathy of LLD are limited, and novel interventions are urgently needed. This proposal is based on the premise that customizing interventions based on theorized brain mechanisms of apathy may increase the potency and scalability of promising therapies. This K23 proposes to conduct a randomized controlled trial evaluating the potential of a customized digital cognitive training (DCT) intervention to target brain network abnormalities in apathy of LLD and reduce symptoms of apathy and related cognitive and behavioral deficits. Eighty-four older adults with major depressive disorder and clinically significant apathy will be randomized to four weeks of a home-based DCT intervention or an active expectancy-matched control. The DCT will involve a suite of exercises designed to engage brain networks disrupted in apathy by targeting cognitive processes (i.e., salience processing, sustained attention, cognitive control) supported by these networks. Aligned with NIMH’s experimental therapeutics approach, we will examine the extent to which a targeted DCT program modulates functional network disturbances in apathy of LLD and improves apathy and associated cognitive deficits. The proposed study will generate preliminary data regarding network targets of a customized digital therapeutic that may translate to mood and cognitive benefits, and may guide future personalization of treatments for motivational disturbances in older adulthood. The training provided through this K23 will advance my knowledge and skillsets in: 1) the design and delivery of a neuroscience-informed, virtually-delivered intervention targeting a distinct subtype of depressed older adults; 2) use of functional MRI to probe mechanisms of action of the proposed DCT; 3) advanced longitudinal modeling of clinical trial data to assess trajectories of change and identify predictors of response and; 4) generating an R-series experimental therapeutics target engagement application. This training will prepare me for an independent research career developing and refining neuroscience-based interventions targeting traditionally intractable and functionally impairing mood and cognitive disturbances in older adulthood.


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 = $193,668 )
2026	2026	ADVENTIST HEALTH SYSTEM/SUNBELT INC	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Mental Health Research Grants	000	4	3/24/2026	NON-COMPETING CONTINUATION	$193,668
														Subtotal = $193,668

Issue Date FY: 2025 ( Subtotal = $194,090 )
2025	2025	ADVENTIST HEALTH SYSTEM/SUNBELT INC	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Mental Health Research Grants	001	3	3/5/2025	NON-COMPETING CONTINUATION	$194,090
2025	2023	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Mental Health Research Grants	000	1	12/13/2024	NEW	$0
														Subtotal = $194,090

Issue Date FY: 2024 ( Subtotal = $192,534 )
2024	2024	ADVENTIST HEALTH SYSTEM/SUNBELT INC	601 E ROLLINS ST	ORLANDO	FL	32803	ORANGE	USA	Mental Health Research Grants	001	2	5/8/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$192,534
2024	2023	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Mental Health Research Grants	000	1	5/8/2024	NEW	$0
														Subtotal = $192,534

Issue Date FY: 2023 ( Subtotal = $194,839 )
2023	2023	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Mental Health Research Grants	000	1	3/30/2023	NEW	$194,839
														Subtotal = $194,839

Grand Total All Awards = $775,131

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Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics

Award Number: K23MH129882

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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