Multimodale neurobeeldvorming van breinveroudering biomerkers in depressie bij ouderen

Late-life depression (LLD) is often associated with cognitive dysfunction and increases the risk of developing dementia. Neuroimaging studies of depression consistently report lower gray matter volume, most robustly in the temporal lobe. Yet, the chain of events leading to lower gray matter volume in depression is still unresolved. The main goal of this PhD project was therefore to gain insight in the origin of gray matter volume differences in LLD. Given the ambiguous link with AD, investigating AD biomarkers in LLD might shed light on potential contributing factors to gray matter volume changes in LLD. We explored gray matter volume differences in LLD using structural MRI and investigated amyloid (18F-Flutemetamol), tau (18F-MK-6240), and synaptic density (11C-UCB-J) biomarkers using positron emission tomography. Our findings consistently identified reduced gray matter volume in brain regions implicated in AD. However, these volume differences were not accompanied by AD-related pathology (Chapter 4 and Chapter 5) or lower synaptic density (Chapter 6). These results suggest that amyloid, tau and SV2A PET may be valuable in distinguishing LLD and prodromal AD. Whilst underlying neurodegeneration might contribute to some LLD phenomenology, the epidemiological link between AD and LLD might better be explained by common risk factors, than by common neuropathology. Lower GMV in LLD might rather represent a predisposing biological factor, a consequence of accelerated aging, or a dynamic interaction between both that is difficult to disentangle. Investigating LLD both on the individual level and group level while incorporating various biological, psychological, and social factors is essential for future research that seeks specific targets for intervention.