Cognitive outcomes of deep brain stimulation depend on age and hippocampal connectivity in Parkinson's and Alzheimer's disease

INTRODUCTION Here we contrast cognitive outcomes of deep brain stimulation (DBS) in Parkinson's disease (PD) with Alzheimer's disease (AD) to isolate the shared effect of DBS upon cognition while filtering out disease‐specific effects. Based on prior literature, we evaluate how DBS connectivity to the hippocampus influences cognition. We then evaluate how patient factors moderate this relationship. METHODS We studied electrode locations and cognitive outcomes in patients who received subthalamic nucleus (STN) DBS for PD (2 datasets: n = 33, n = 28) or fornix DBS for AD (1 dataset: n = 46). We then investigate the moderating effect of patient factors and similarities across diseases. RESULTS DBS site connectivity to the hippocampus was cognitively deleterious in PD but beneficial in AD. The opposite findings were driven by patient age. This effect was mediated by age‐related hippocampal atrophy. DISCUSSION The shared cognitive effects of DBS across PD and AD depend on hippocampal connectivity and age. Highlights Cognition can be positively or negatively modulated in the same manner across diseases. Contrary to current clinical practice, older Parkinson's disease (PD) patients may benefit from deep brain stimulation (DBS). Our results support limiting enrollment to patients over 65 for Alzheimer's disease (AD) DBS, an emerging therapy currently in a phase 3 clinical trial. Hippocampal volume mediates the impact of DBS, suggesting patient atrophy must be considered in patient‐specific care.