# Cognitive Remediation of Cognitive Control in Late-Life Depression

> **NIH NIH K23** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2022 · $206,114

## Abstract

Dr. Manning is a licensed clinical neuropsychologist who specializes in the cognitive evaluation of older adults.
The focus of his clinical practice and clinical-research is cognitive disorders and depression in the elderly. This
K23 Award is a critical step toward his career as an independent investigator focused on understanding and
modifying pathophysiologic processes of late-life depression (LLD). LLD is a risk state for later dementia. It is
thought that frontolimbic brain changes result in both depression and cognitive weaknesses that interact to
increase the likelihood of dementia in LLD. Mild impairments in executive functions (EF) appear especially
relevant to LLD. Weaknesses in EF are common in LLD and predictive of treatment resistance and a later
dementia diagnosis. The process appears to be dynamic, in the sense that decrements in EF promote
depressive symptoms, and increases in depression lead to greater impairment in EF. One way to intervene
would thus be to address depressive symptoms, e.g., with antidepressants and / or psychotherapy. However,
antidepressants have rather limited efficacy and a delayed clinical response in LLD. Furthermore,
antidepressants and psychotherapy do not consistently improve EF post-treatment. The other means to
intervene, then, would be to target EF. We propose to use computerized cognitive remediation to change EF,
depression, and executive control connectivity and explore whether this change is associated with changes in
limbic connectivity and long-term cognitive decline in LLD.
With the resubmission of this Award application, Dr. Manning proposes a training and research plan that
provides a foundation from which to study mechanisms related to treatment response and cognitive decline in
LLD. He has four training goals: 1) Expand his knowledge of mechanisms affecting treatment response and
cognitive decline in LLD. 2) Develop expertise in the acquisition and analysis of structural and functional MRI.
3) Obtain training in the utilization and evaluation of cognitive remediation interventions, and 4) Learn clinical
trial design and analysis of mechanisms of therapeutic change in LLD. In response to the Reviewers'
thoughtful critiques, the training plan now emphasizes coursework in clinical neuroscience, MRI analysis, and
randomized trials, as well as workshops in preclinical dementia identification. Dr. Manning pays close attention
to the use of structural and functional MRI, sensitive cognitive assessment, and longitudinal follow-up as a
means to identify LLD patients at risk for cognitive decline. Beyond providing excellent training, this research
approach has the strong potential to shed light on the pathophysiology of LLD.

## Key facts

- **NIH application ID:** 10451634
- **Project number:** 5K23MH118420-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Kevin James Manning
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $206,114
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451634

## Citation

> US National Institutes of Health, RePORTER application 10451634, Cognitive Remediation of Cognitive Control in Late-Life Depression (5K23MH118420-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10451634. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*