Longitudinal Observational Biomarker Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test whether treatment-resistant late life depression is associated with declines in memory and attention and brain structure and function.

Detailed Description
-----------------
The purpose of this study is to test whether treatment-resistant late life depression is associated with declines in memory and attention and brain structure and function. The study will also test if changes in brain structure and function are associated with decreases in memory. In this study, investigators will conduct a series of assessments/tests, mainly brain imaging and assessments of participant's memory and attention, to better understand how depression is linked to memory and thinking in older persons. Investigators hope that their study will help the scientific community to understand why some people with depressive symptoms that are resistant to treatment in late-life experience declines in their memory and attention and whether effective treatment of such depression reduces that risk. Finally, investigators hope that this study will eventually lead to the development of better treatment options.

Official Title
-----------------
Neurocognitive and Neuroimaging Biomarkers: Predicting Progression Towards Dementia in Patients With Treatment-resistant Late-life Depression (OPTIMUM-Neuro Study)

Conditions
-----------------
Depression, Dementia, Mild Cognitive Impairment

Intervention / Treatment
-----------------
* Behavioral: Mechanisms of Late life depression (LLD)-dementia through functional Magnetic Resonance Imaging (fMRI)
* Behavioral: Neuropsychological Data
* Behavioral: Clinical Scales


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged 60 and older Current Major Depressive Disorder (MDD) Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher Exclusion Criteria: Dementia Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms. High risk for suicide and unable to be managed safely in the clinical trial Non-correctable, clinically significant sensory impairment interfering with participation Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. Moderate to severe substance or alcohol use disorder Seizure disorder. Parkinson's Disease Individuals with any contraindications to MRI

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Behavioral: Mechanisms of Late life depression (LLD)-dementia through functional Magnetic Resonance Imaging (fMRI)|Analyzing mechanisms of the LLD-dementia relationship through fMRI acquisitions and analyses, to capture the specific brain networks implicated in executive function and episodic memory decline.|
|Behavioral: Neuropsychological Data|Neuropsychological Data, including Montreal Cognitive Assessment (MoCA), Wide Range Achievement Test-4 (WRAT-4) Reading subtest, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Delis-Kaplan Executive Function System (D-KEFS) (Color Word Interference, Trail Making and Verbal Fluency).|
|Behavioral: Clinical Scales|Clinical scales, including the Everyday Cognition Scale (E-Cog), Global Clinical Dementia Rating (CDR), Performance Assessment of Selfcare Skills (PASS)--CIADL (Cognitive Instrumental Activities of Daily Living) Short version, Patient Health Questionnaire (PHQ-9), and Suicide Risk Assessments (Suicide Questions, Baseline Suicidal Ideation, Suicide Intent Scale, Beck Lethality Scale, Decision Outcome Inventory, Columbia-Suicide Severity Rating Scale, and High Suicide Risk Protocol).|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent Depression Leading to Change in Cognition | To test whether persistent (non-remitting) depression has the ability to change cognition and lead to greater cognitive decline, and greater degradation of neural circuitry | Baseline, 6-months, 24-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Neural Circuity | To test whether greater degradation of neural circuitry is associated with greater cognitive decline | Baseline, 6-months, 24-months |