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Neurocognitive Outcomes of Depression in the Elderly (NCODE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00570583
First received: December 7, 2007
Last updated: April 25, 2017
Last verified: April 2017
  Purpose

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.


Condition
Major Depression
Dementia

Study Type: Observational
Study Design: Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Clinical Studies of Mental Illness Not Involving Treatment Development, Efficacy, or Effectiveness Trials Phenotype-genotype Predictors of Cognitive Outcomes in Geriatric Depression

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Change in Depression status (measured by Montgomery Asberg Depression Rating Scale) [ Time Frame: 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 ]
  • Development of dementia (Determined by Clinical Consensus Conference) [ Time Frame: once per year, up to 14 years ]

Secondary Outcome Measures:
  • 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 ]
  • Change in Impairment in Instrumental or Basic Activities of Daily Living [ Time Frame: 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 ]

Biospecimen Retention:   Samples With DNA
serum, white cells

Estimated Enrollment: 795
Study Start Date: December 1995
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
Groups/Cohorts
Depressed
Older individuals with major depression
Non-depressed
Older individuals without psychiatric disorder

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

  Eligibility

Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Primary care clinic Outpatient psychiatry clinic Inpatient psychiatry clinic Self-referral
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570583

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Guy G Potter, PhD Duke University
  More Information

Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00570583     History of Changes
Other Study ID Numbers: Pro00006424
1R01MH108560-01 ( US NIH Grant/Contract Award Number )
0625
Study First Received: December 7, 2007
Last Updated: April 25, 2017

Keywords provided by Duke University:
Depression
Cognitive impairment
Dementia
Neuroimaging
Genetics

Additional relevant MeSH terms:
Depression
Depressive Disorder
Dementia
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders

ClinicalTrials.gov processed this record on April 28, 2017