Late-Life Depression Study Launching in Belgium: The Published Protocol

Out on PubMed, from researchers in Belgium, is this paper:

 The Leuven late life depression (L3D) study: PET-MRI biomarkers of pathological brain ageing in late-life depression: study protocol.

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.BMC Psychiatry. 2021 Jan 28;21(1):64. doi: 10.1186/s12888-021-03063-y.PMID: 33509135

The abstract is copied below:

Background: Major depressive disorders rank in the top ten causes of ill health in all but four countries worldwide and are the leading cause of years lived with disability in Europe (WHO). Recent research suggests that neurodegenerative pathology may contribute to the development of late-life depression (LLD) in a sub-group of patients and represent a target for prevention and early diagnosis. In parallel, electroconvulsive therapy (ECT), which is the most effective treatment for severe LLD, has been associated with significant brain structural changes. In both LLD and ECT hippocampal volume change plays a central role; however, the neurobiological mechanism underlying it and its relevance for clinical outcomes remain unresolved.

Methods: This is a monocentric, clinical cohort study with a cross-sectional arm evaluating PET-MR imaging and behavioural measures in 64 patients with LLD compared to 64 healthy controls, and a longitudinal arm evaluating the same imaging and behavioural measures after 10 ECT sessions in 20 patients receiving ECT as part of their normal clinical management. Triple tracer PET-MRI data will be used to measure: hippocampal volume (high resolution MRI), synaptic density using [11C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, tau pathology using [18F]MK-6240, and cerebral amyloid using [18F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain. Additional MRI measures and ultrasound will assess cerebral vascular structure and brain connectivity. Formal clinical and neuropsychological assessments will be conducted alongside experience sampling and physiological monitoring to assess mood, stress, cognition and psychomotor function.

Discussion: The main aim of the study is to identify the origin and consequences of hippocampal volume differences in LLD by investigating how biomarkers of pathological ageing contribute to medial temporal lobe pathology. Studying how synaptic density, tau, amyloid and vascular pathology relate to neuropsychological, psychomotor function, stress and ECT, will increase our pathophysiological understanding of the in vivo molecular, structural and functional alterations occurring in depression and what effect this has on clinical outcome. It may also lead to improvements in the differential diagnosis of depression and dementia yielding earlier, more optimal, cost-effective clinical management. Finally, it will improve our understanding of the neurobiological mechanism of ECT.

Trial registration: ClinicalTrials.gov Identifier: NCT03849417 , 21/2/2019.

Keywords: Ageing; Amyloid; Brain; ECT; Late life depression; MRI; Neurodegeneration; PET; Synaptic density; Tau.

And from the text:

                           

This publication is a preview of a proposed study. The researchers are a very experienced and accomplished group, but recruitment for such an ambitious study will, nonetheless, be very challenging. This is the key ECT sentence: "The primary outcome measures for the longitudinal part of the study are change in hippocampal volume, tau and synaptic density following ECT." So the hope is to better define what neuronal mechanism is responsible for the now well-established finding of transient hippocampal volume increase after a course of ECT.

I wish these investigators well and look forward to discussing their results in the future on this blog.

I recommend a full read for those interested in an excellent discussion of brain ageing and late-life depression research methodology (~30 minutes).