Non-Amyloid Pathological Brain Aging in Late Life Depression

Understanding the aetiology of medial temporal lobe (MTL) pathology in severe late-life depression (LLD) is crucial for improving diagnostic specificity with respect to dementia and for optimising treatment. Given the role of tau in neurodegenerative diseases and our recent finding that hippocampal atrophy in LLD is not related to brain amyloid, we will study non-amyloid pathological brain aging in LLD using PET-MRI neuroimaging. We will investigate the relationship between white matter lesions, which are implicated in LLD, synaptic density in the hippocampus, and tau pathology and the association with stress. Importantly, we will also study how these findings impact upon treatment and behaviour, by investigating (a) if electroconvulsive therapy alters hippocampal synaptic density and whether this explains its therapeutic effect and its effect on hippocampal volume, and (b) if MTL atrophy in LLD is associated with failure of the emotional positivity effect that characterizes normal aging.

Keywords:hippocampal volume, tau pathology, synaptic density, late life depression, PET MR imaging, stress and aging

Disciplines:Psychiatry and psychotherapy, Nursing, Other paramedical sciences, Clinical and counselling psychology, Other psychology and cognitive sciences