Neurocognitive Outcomes of Depression in the Elderly (NCODE)
This study seeks to examine clinical, genetic, and neuroanatomical variables related to mood and cognitive outcomes of depression in late life. We plan to study the following SPECIFIC AIMS:
Aim 1. To compare cognitive outcomes among older adults with and without depression, and to examine depression and cognitive outcomes in patients with cognitive impairment or neuroimaging changes.
Aim 2. To examine the role of genes in long-term depression outcomes in the elderly.
Aim 3. To determine neuroanatomical and neuropathological correlates of late-life depression outcomes.
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Geriatric Depression: Risk Factors for Adverse Outcomes|
- Change in Depression status (measured by Montgomery Asberg Depression Rating Scale) [ Time Frame: Minimum of once per year, up to 21 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Development of dementia (Determined by Clinical Consensus Conference) [ Time Frame: once per year, up to 14 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Change in Impairment in Instrumental or Basic Activities of Daily Living [ Time Frame: at least once per year, up to 21 years ] [ Designated as safety issue: No ]
- Packing density of prefrontal cortex neurons with pyramidal morphology in post-mortem neuroanatomical studies [ Time Frame: once post-mortem ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
serum, white cells
|Study Start Date:||December 1995|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Older individuals with major depression
Older individuals without psychiatric disorder
We will test the following hypotheses:
Hypothesis 1. Compared with non-depressed elderly controls, depressed elderly patients will have an increased incidence of development of mild cognitive impairment and dementia.
Hypothesis 2. Depressed subjects with mild cognitive impairment will have a worse depression course compared with depressed subjects who do not have mild cognitive impairment.
Hypothesis 3. Depressed subjects with worsening deep white matter disease and smaller hippocampal volumes on longitudinal (baseline to two year) magnetic resonance imaging brain scans will have a worse depression course and more cognitive decline compared with depressed subjects without these brain changes.
Hypothesis 4. Depressed subjects with the 5HTTLPR short allele will have a worse depression course compared with depressed subjects without these risk genes.
Hypothesis 5. Depressed subjects with the apolipoprotein E (APOE) epsilon-4 allele and vascular risk gene polymorphisms such as ACE receptor will have an increased risk of cognitive decline compared with depressed subjects without these risk genes.
Hypothesis 6. Compared with brains of non-depressed controls, brains of depressed subjects will demonstrate increased density of blood vessels in the prefrontal cortex, including orbital frontal cortex and dorsolateral prefrontal cortex.
Hypothesis 7. Compared with brains of non-depressed controls, brains of depressed subjects will demonstrate decreased packing density of prefrontal cortex neurons with pyramidal morphology.
Hypothesis 8. Compared with non-demented depressed subjects, depressed individuals who become demented will have more neuritic plaques, neurofibrillary tangles and cerebrovascular pathology.
We will examine secondary aims related to 1) mortality and 2) social factors, with the following hypotheses:
- Depressed subjects with a larger increase in volume of hyperintensities will have a higher mortality rate.
- Subjects with poor social support and functional status will have worse depression and cognitive outcomes.
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||John L Beyer, MD||Duke University|