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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Depression
• Intervention / Treatment: Other: ECT

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 128

Contacts and Locations

• Study Contact: Name: Mathieu Vandenbulcke, MD, PhD; Phone Number: +32 16 3 48005; Email: mathieu.vandenbulcke@uzleuven.be
• Study Contact Backup: Name: Filip Bouckaert, MD, PhD; Phone Number: +32 2 758 0891; Email: filip.bouckaert@upckuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium
    • Recruiting
    • UZ Leuven
    • Contact: Mathieu Vandenbulcke, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

A consecutive series of hospital in-patients with late-life depression will be recruited from the Department of Old Age Psychiatry within the University Psychiatric Center, KU Leuven, Belgium. Healthy controls will be recruited from the community by researchers affiliated with the Department of Old Age Psychiatry Department & Translational Neuropsychiatry using traditional means e.g. flyer. All participants will provide written informed consent prior to enrollment in the study in accordance with the Declaration of Helsinki.

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Mathieu Vandenbulcke, MD, PhD, UZ Leuven / UPC-KU Leuven

Publications and helpful links

General Publications

• Emsell L, Laroy M, Van Cauwenberge M, Vande Casteele T, Vansteelandt K, Van Laere K, Sunaert S, Van den Stock J, Bouckaert F, Vandenbulcke M. The Leuven late life depression (L3D) study: PET-MRI biomarkers of pathological brain ageing in late-life depression: study protocol. BMC Psychiatry. 2021 Jan 28;21(1):64. doi: 10.1186/s12888-021-03063-y.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 21, 2019

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 24, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Aging; Neuroimaging; Electroconvulsive therapy; Late-life depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: S61968

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The nature of anonymized IPD data that may be made available will be determined on an ad hoc basis and in adherence with the terms of the informed consent provided by the participants and advice from the local ethics committees and university technology transfer office.