Brain Imaging Biomarkers of Pathological Brain Aging in Late-life Depression

Study Overview
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Brief Summary
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This study investigates the relationships and differences in PET-MRI brain imaging biomarkers of abnormal aging and behavioral measures in late life depression compared to healthy controls, and evaluates relationships and differences in the same imaging and behavioral measures following electroconvulsive therapy. The study tests the hypotheses that late-life depression will be associated with higher levels of accelerated aging and brain disease biomarkers, and that electroconvulsive therapy works by stimulating the reorganization of brain tissue.The data collected with contribute to improved knowledge about the neurobiology of late-life psychopathology and its treatment.

Detailed Description
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This clinical study is a combined single-center, cohort study with a (1) cross-sectional arm evaluating relationships and differences in PET-MR imaging and behavioral measures in 64 patients with late life depression (LLD) compared to 64 healthy controls, and (2) a longitudinal arm evaluating relationships and differences in imaging and behavioral measures in 20 patients receiving ECT as part of their normal clinical management. The study will utilise three PET tracers: (1) [11C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, to estimate synaptic density (2) [18F]MK-6240, which targets tau associated with neurofibrillary tangles, to assess the presence of tau pathology and (3) [18F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain, to assess the presence of cerebral amyloidosis. The main aim of the study is to clarify how hippocampal synaptic density, tau, amyloid and white matter lesions, relate to neuropsychological function, stress and ECT in late life depression.

Official Title
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PET-MRI Biomarkers of Pathological Brain Aging in Late-life Depression

Conditions
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Depression

Intervention / Treatment
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* Other: ECT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of late-life depression according to DSM 5 (patients only) Age over 60 years old Judged to be in good physical health by the investigator on the basis of medical history Exclusion Criteria: history or evidence of psychiatric disease, as assessed by clinical interview (healthy controls only). history of major other neurological disorder, or major internal pathology that may make him/her unfit for participation according to the interpretation by the investigator (including cardiac, lung, haematological, gastro-intestinal disorders or cancer); current user (including ''recreational use'') of any illicit drugs,including cannabis, or has a history of drug or alcohol abuse; had exposure to ionizing radiation (> 1 mSv) in other research studies within the last 12 months; has a contra-indication for MRI scanning; suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures; cannot lie still for 60 minutes inside the scanner; does not understand the study procedures unwilling or unable to perform all of the study procedures, or is considered unsuitable in any way by the principal investigator; underwent ECT within the last 3 months before enrollment (patients)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Late-life Depression<br>Patients aged over 60 years old with severe depression | |
| Late-life Depression (ECT)<br>Patients aged over 60 years old with severe depression who are referred for treatment with electroconvulsive therapy | Other: ECT<br>* ECT administered as part of normal clinical management<br>|
| Healthy Controls<br>Healthy volunteers over 60 years old who will form a comparison group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between synaptic density and hippocampal volume in LLD | Cross-sectional association between [11C]UCB-J binding (SUVR) and MRI-based assessment of hippocampal volume | 1 day | 
| Relationship between tau and hippocampal volume in LLD | Cross-sectional association between [18F]MK-6240 binding (SUVR) and MRI-based assessment of hippocampal volume | 1 day | 
| Relationship between tau and white matter (wm) pathology in LLD | Cross-sectional association between [18F]MK-6240 binding (SUVR) and MRI measures of white matter pathology (T2-FLAIR WMH/lesions, diffusion MRI measures in temporal lobe tracts) | 1 day | 
| Effect of tau on medial temporal neural responses to emotional stimuli and functional connectivity in LLD | Cross-sectional association between [18F]MK-6240 binding (SUVR), fMRI based assessment of the emotion positivity effect, and fMRI derived resting state brain networks. | 1 day | 
| Relationship between medial temporal pathology and stress | Association between [18F]MK-6240 binding (SUVR), hippocampal volume (MRI) and reactivity to stress (EMA) and wristband monitoring of heart rate and skin conductance. | 1 week | 
| Relationship between hippocampal volume increase following ECT and changes in synaptic density and tau | Association between change in [11C]UCB-J and [18F]MK-6240 binding (SUVR) and MRI-based assessment of hippocampal volume one week following last ECT | 8 weeks | 
| Amyloid changes following ECT | Change in [18F] Flutemetamol one week following the last ECT treatment | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Late-life depression, Electroconvulsive therapy, Neuroimaging, Aging