Objective: To investigate differences in the association of motor signs with synaptic density, gray matter volume and white matter lesion volume in patients with late life depression compared to healthy older adults.

Background: Motor signs are common in older persons with a major depressive disorder (“late life depression”). They may clinically resemble parkinsonism and are associated with falls. It is unclear whether motor signs in late life depression are caused by global brain aging and/or by neurobiological changes specific to the depression.

Method: 75 participants (41 healthy controls, 34 patients) aged ≥ 60 years were included from the monocentric Leuven Late Life Depression study. Motor assessment included the MDS-Unified Parkinson’s Disease Rating Scale motor part III (MDS-UPDRSIII), Scale for Assessment and Rating of Ataxia (SARA), gait analysis and fine motor analysis using a digital tablet drawing task. Brain SV2A binding as a proxy for synaptic density was determined in structural MRI defined cortical and subcortical volumes-of-interest using¹¹C-UCB-J PET in 62 participants (25 patients). T1 and FLAIR MR images were used to quantify gray matter and white matter lesion volume in 69 participants (32 patients). Multiple linear regression analyses were performed with motor outcome as the dependent variable, diagnosis and volume of interest ¹¹C-UCB-J SUVR plus their interaction, age, whole brain white matter hyperintensities and gray matter volumes of interest as independent variables. Analyses were performed with and without partial volume correction of PET data. Bonferroni correction was applied to the overall regression model F-statistic.

Results: Patients (mean age 73±6 years, 68% female, MADRS 27.9±11.1) were significantly impaired on all motor assessments, including the MDS-UPDRSIII (mean 25.6±6.1), SARA (mean 6.1±4.1) and gait velocity (mean 0.81±0.30 m/s). Specifically in patients, right globus pallidus synaptic density was associated with MDS-UPDRSIII score and drawing speed; basal ganglia and thalamus gray matter volume predicted gait and balance outcome; and white matter hyperintensity volume predicted MDS-UPDRSIII score.

Conclusion: Motor signs in late life depression are associated with differences in synaptic density and gray matter volume in basal ganglia-thalamic structures.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alterations-in-basal-ganglia-synaptic-density-and-thalamic-gray-matter-volume-are-associated-with-motor-signs-in-late-life-depression-an-11c-ucb-j-pet-mr-study/