Ignite Creation Date:
2024-05-05 @ 6:57 PM
Last Modification Date:
2024-10-26 @ 9:38 AM
Study NCT ID:
NCT00570583
Status:
COMPLETED
Last Update Posted:
2020-08-05
First Post:
2007-12-07
Brief Title:
Neurocognitive Outcomes of Depression in the Elderly
Sponsor:
Duke University
Organization:
Duke University
Study Overview
Official Title:
Clinical Studies of Mental Illness Not Involving Treatment Development Efficacy or Effectiveness Trials Phenotype-genotype Predictors of Cognitive Outcomes in Geriatric Depression
Status:
COMPLETED
Status Verified Date:
2020-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NCODE
Brief Summary:
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
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
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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 0625 | US NIH GrantContract | None | httpsreporternihgovquickSearch1R01MH108560-01 |
| 1R01MH108560-01 | NIH | None | None |