Motor signs in late life depression relate to altered subcortical synaptic density and gray matter volume: an...

Motor signs are common in patients with a major depressive disorder (MDD) and associated with functional disability and falls. They appear to be more pronounced in patients with late life depression, but it is unclear whether this is caused by global brain aging or by a specific pathology associated with depression. We therefore sought to investigate associations between motor signs in late life depression and aging related changes in synapses, gray and white matter. From the monocentric Leuven Late Life depression study, we included 75 participants (41 healthy controls, 34 currently depressed MDD patients) aged ≥ 60 years. Motor assessment included the MDS-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRSIII), Scale for Assessment and Rating of Ataxia (SARA), gait analysis and digitized drawing. Brain synaptic vesicle glycoprotein 2A binding as a proxy for synaptic density was determined in predefined cortico-subcortical volumes of interest (VOI) using ¹¹C-UCB-J PET in 62 participants (25 patients). Brain T1 and FLAIR MR images were used to quantify gray matter volume and white matter hyperintensity volume in 69 participants (32 patients). Multiple linear regression analyses were performed with motor outcome as the dependent variable, diagnosis and VOI ¹¹C-UCB-J SUVR and their interaction, age, whole brain white matter hyperintensity volume and gray matter VOI as independent variables. The study demonstrated that patients had significant impairments on all motor assessments, compared to healthy controls. Specifically in patients, right globus pallidus synaptic density was associated with MDS-UPDRSIII score and drawing speed; thalamic gray matter volume predicted SARA score, gait and drawing speed; and white matter hyperintensity volume predicted MDS-UPDRSIII score. We conclude that motor signs in late life depression are associated with specific synaptic density and gray matter volume differences in basal ganglia-thalamic structures.