Importance of Proactive Treatment of Depression in Lewy Body Dementias: The Impact on Hippocampal Neurogenesis and Cognition in a Post-Mortem Study

Abstract

Objective: To examine the impact of selective serotonin reuptake inhibitors (SSRIs) and depression on neurogenesis and cognition in dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). Methods: Late-stage progenitor cells were quantified in the subgranular zone (SGZ) of the hippocampal dentate gyrus of DLB/PDD patients (n = 41) and controls without dementia (n = 15) and compared between treatment groups (unmedicated, SSRIs, acetyl cholinesterase inhibitors [AChEIs], combined SSRIs and AChEIs). Results: DLB/PDD patients had more doublecortin-positive cells in the SGZ compared to controls. The doublecortin-positive cell count was higher in the SGZ of patients treated with SSRIs and correlated to higher cognitive scores. Conclusion: SSRI treatment was associated with increased hippocampal neurogenesis and preservation of cognition in DLB/PDD patients.

REM Sleep Behavior Disorder (RBD) in Dementia with Lewy Bodies (DLB)

“…Regarding the management of depression in DLB patients, serotoninergic-targeted therapy would be an option based on individual response. Furthermore, selective serotonin reuptake inhibitor treatment may even be associated with increased hippocampal neurogenesis and preservation of cognition in DLB/PDD patients according to a recent study [ 27 ]. Extrapyramidal symptoms Previous studies mostly revealed no benefits or mild improvement with levodopa treatment in motor symptoms of DLB patients [ 28 , 29 ].…”

Adult Human Hippocampal Neurogenesis: Controversy and Evidence

“…On the other hand, Boldrini and colleagues [4] In contrast to Sorrells and colleagues' observations, Boldrini and colleagues were able to detect all of the immature and mature cell types in the adult human DG as shown in previous other studies [2,7,8]. Furthermore, they did not observe a substantial decline in the number of these cells with age.…”

Dopaminergic Changes in the Subgenual Cingulate Cortex in Dementia with Lewy Bodies Associates with Presence of Depression

“…Individuals with DLB are at high risk of developing major depression as part of the syndrome, with depression being present from an early stage (Fujishiro et al 2015) with a significant impact on quality of life (Gatt et al 2017; McKeith et al 2017). Depression in DLB correlates with α-synuclein pathology and Lewy bodies in late onset MDD found in older populations, indicating that α-synuclein pathology may be a significant factor in development of MDD in older individuals (Nunes et al 2022).…”