# 1/2 Phenotype Predictors of Cognitive Outcomes in Geriatric Depression

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $356,420

## Abstract

Among older adults, major depressive disorder with cognitive impairment (CI) is associated with increased
disability, higher healthcare utilization, and increased risk of dementia. From a clinical standpoint, gaining
knowledge about proximate (i.e., within 5 years) predictors of adverse cognitive outcomes among currently
depressed older adults is crucial to timely and targeted intervention for at-risk individuals. From a scientific
standpoint, identifying phenotypes and genotypes associated with cognitive diagnostic outcomes—both
positive and negative—will advance research on mechanisms, prevention, and treatment. The NIMH-
supported Neurocognitive Outcomes of Depression in the Elderly (NCODE) Study at Duke University and
Neurobiology of Late-life Depression (NBOLD) Study at the University of Connecticut (UConn) are among the
few prospective studies that include both longitudinal cognitive diagnostic outcomes and a formal clinical
diagnosis of major depression in late life (LLD). In addition, these studies share common features related to
clinical and cognitive assessment, neuroimaging, and genetic analysis. Consistent with PAR-14-165, the
objective of the proposed clinical collaboration is to complete a two-site prospective study of cognitive
diagnostic outcomes of LLD that will capitalize on the power of the combined data to: 1) identify clinical and
biological phenotypes that predict cognitive diagnostic outcomes, and 2) understand the neural and genetic
mechanisms associated with them. We seek support to extend current 2-year study enrollments to a 5-year
clinical follow-up period in order to increase sample sizes to identify clinical, neuroimaging and genetic
predictors of three key diagnoses our data find in 90% of cognitive diagnostic outcomes over a 5-year period:
1) normal cognition (CN), 2) persistent cognitive impairment without dementia (PCI), and 3) Alzheimer’s
disease (AD). Our central hypothesis is that the 5-year likelihood of each cognitive diagnostic outcome is
associated with distinct clinical, cognitive, and neural phenotypes during acute LLD, which in turn have distinct
genotypic correlates. Specifically, CN individuals will have earlier first onset of depression relative to AD, report
greater negative life stress compared to AD and PCI, and have greater white matter integrity; additionally, CN
will be associated with the AA genotype of COMTval158met, which may confer both neuroprotection and
higher sensitivity to stress. PCI will be associated with earlier age of depression onset relative to AD, greater
frailty, and lesser white matter integrity than NC. AD will be associated with later age of depression onset,
appetite/weight loss, lower anxiety, smaller hippocampal volume, and memory impairment. We propose to test
all of these putative associations in our Specific Aims. The proposed research will identify and integrate
biological and behavioral markers associated with proximate cognitive diagnostic outcomes in LLD (NIMH
St...

## Key facts

- **NIH application ID:** 9955354
- **Project number:** 5R01MH108578-05
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** DAVID C. STEFFENS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $356,420
- **Award type:** 5
- **Project period:** 2016-09-13 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955354

## Citation

> US National Institutes of Health, RePORTER application 9955354, 1/2 Phenotype Predictors of Cognitive Outcomes in Geriatric Depression (5R01MH108578-05). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9955354. Licensed CC0.

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