Cortical Changes Associated with Depression and Antidepressant Use in Alzheimer and Lewy Body Dementia: An MRI Surface-based Morphometric Study

Context: Depression is common in dementia, especially in the early stages, with important clinical implications, but the etiology is unknown and most likely heterogeneous. Antidepressant use in the elderly without dementia has previously been shown to be associated with high risks of adverse events and with structural brain alterations. Objective: To investigate cortical changes associated with depression and antidepressant use in patients with mild Alzheimer's disease (AD) and Lewy body dementia (LBD). Methods: 74 subjects with mild AD and LBD from geriatric and psychiatry outpatient clinics in Western Norway were included. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depression. Automatic preprocessing using Freesurfer included steps for white and grey matter surface reconstruction. The resulting cortical thickness was analyzed using linear modeling. Results: Clusters of depression-associated thinning were found in prefrontal and temporal areas. Treatment-associated thinning was observed in the parahippocampal region and was significant even after correction for age, sex, AD/LBD diagnosis, and MADRS scores. Conclusion: Depression in mild AD and LBD is associated with cortical thinning in prefrontal and temporal areas. The findings suggest that depressive symptoms in mild dementia could develop due to neurodegeneration in the same neural circuits that are critical for depression across different brain disorders. Antidepressant use in patients with mild AD and LBD is associated with parahippocampal thinning. Taken together with low efficacy of antidepressants in cognitively impaired patients and high risks of adverse events, our results suggest a need to re-evaluate the treatment approaches for depression and the role of antidepressants in patients with dementia.