Neurocognitive Outcomes of Depression in the Elderly (NCODE)

August 4, 2020 updated by: Duke University

Clinical Studies of Mental Illness Not Involving Treatment Development, Efficacy, or Effectiveness Trials Phenotype-genotype Predictors of Cognitive Outcomes in Geriatric Depression

Late-life depression (LLD) and cognitive impairment (CI) are significant public health problems among older adults, and their co-occurrence markedly increases disease burden and dementia risk. This highlights the importance of identifying and treating CI in LDD; however, current lack of reliable prognostic information from clinical, neuroimaging, and genetic data impedes research on targeted prevention and treatment. Two critical ways to close current knowledge gaps in predicting cognitive diagnostic outcomes of LLD involve: 1) increasing the number of diagnostic cases available to existing studies, and 2) using those studies to identify clinical, imaging, and genetic predictors that will improve future diagnosis. We intend to do both in the current proposal. We plan to study the following SPECIFIC AIMS:

Aim 1: Identify baseline clinical-behavioral predictors of cognitive diagnostic outcomes in LLD.

Working hypothesis: During acute LLD, CN will be associated with more frequent EOD and higher negative life stress than PCI and AD; PCI will be associated with EOD and higher frailty than CN and AD; AD will be associated with LOD, greater appetite loss, lower anxiety, and greater memory impairment than CN and PCI.

Aim 2: Use multimodal neuroimaging at baseline to identify patterns associated with cognitive diagnostic outcomes in individuals with LLD. Working Hypothesis: CN will be associated with greater white matter integrity compared with PCI and AD; PCI will be associated with lower white matter integrity and network abnormalities in anterior cingulate cortex compared with CN; AD will be associated with lower hippocampal volume compared with CN and PCI.

Aim 3: (exploratory): Explore interrelationships among candidate genes, cognitive diagnostic outcomes, and proposed phenotypic components relevant to LLD. Exploratory Hypotheses: 1) COMT val158met polymorphism will be associated with CN; 2) 5-HTTPRL and APOE ε2 polymorphisms will be associated with frailty; 3) genetic variation (SNPs) in TPH2 and AGTR1 will be associated with risk factors of AD: LOD, episodic memory, hippocampal volume, and appetite loss.

Study Overview

Status

Completed

Conditions

Detailed Description

Central hypothesis: 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 (EOD) relative to AD, more negative life stress during acute depression compared with AD and PCI, and greater white matter integrity; CN will also be associated with the AA genotype of the COMT val158met polymorphism, which may confer both neuroprotection and higher stress sensitivity. PCI will have more EOD relative to AD, greater frailty, and lower white matter integrity than NC. AD will be associated with later age of depression onset (LOD), greater appetite loss, lower anxiety, smaller hippocampal volume, and greater memory impairment. To test these hypotheses, we propose the following

Study Type

Observational

Enrollment (Actual)

795

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Primary care clinic Outpatient psychiatry clinic Inpatient psychiatry clinic Self-referral

Description

Inclusion Criteria:

For depressed group:

  1. Age > 60 years
  2. Major depression, single episode or recurrent
  3. Ability to read and write English
  4. MMSE >25
  5. Willingness to participate in the follow-up study for at least two years.

For non-depressed group:

  1. Age > 60 years
  2. Ability to read and write English
  3. MMSE >25
  4. Willingness to participate in the follow-up study for at least two years.

Exclusion Criteria:

  1. Lifetime alcohol or drug dependence
  2. conditions associated with MRI abnormalities such hydrocephalus, benign and cancerous brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia, demyelinating diseases, etc.
  3. endocrine disorder other than diabetes mellitus)
  4. Any physical or intellectual disability that may affect completion of self rating instruments
  5. Established clinical diagnosis of dementia
  6. Other primary psychiatric disorders, including panic disorder, social phobia, OCD, non-affective psychosis (including schizo-affective disorder), schizophrenia, bipolar disorder
  7. Any metal or pacemaker in the body which precludes MRI.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Depressed
Older individuals with major depression
Non-depressed
Older individuals without psychiatric disorder

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in Depression status (measured by Montgomery Asberg Depression Rating Scale)
Time Frame: Minimum of once per year, up to 21 years
Minimum of once per year, up to 21 years
Change in Cognitive impairment (as measuring using cognitive tests including those found in the CERAD battery)
Time Frame: Once per year, up to 21 years
Once per year, up to 21 years
Development of dementia (Determined by Clinical Consensus Conference)
Time Frame: once per year, up to 14 years
once per year, up to 14 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in Cognition (as measured by tests including those in the CERAD battery) Change in Brain MRI markers (e.g., volume of white matter and gray matter lesions)
Time Frame: once per year, up to 21 years
once per year, up to 21 years
Change in Impairment in Instrumental or Basic Activities of Daily Living
Time Frame: at least once per year, up to 21 years
at least once per year, up to 21 years
Packing density of prefrontal cortex neurons with pyramidal morphology in post-mortem neuroanatomical studies
Time Frame: once post-mortem
once post-mortem

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Guy G Potter, PhD, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1995

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

December 7, 2007

First Submitted That Met QC Criteria

December 7, 2007

First Posted (Estimate)

December 11, 2007

Study Record Updates

Last Update Posted (Actual)

August 5, 2020

Last Update Submitted That Met QC Criteria

August 4, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00006424
  • 0625
  • 1R01MH108560-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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