A study presented at the recent American Academy of Neurology (AAN) annual meeting (13–18 April, Denver, USA) has gone some way to elucidating how two factors—patient age, and connectivity of electrodes to the subiculum-retrosplenial cortex (SBC-RSC)—may impact the cognitive effects of deep brain stimulation (DBS) among Parkinson’s and Alzheimer’s patients.
Delivering these findings on behalf of his co-investigators, Calvin Howard (Harvard Medical School, Boston, USA) outlined that he and his colleagues endeavoured to gain a better understanding of how patient age and electrode connectivity influence various cognitive outcomes with DBS across both of these neurological diseases.
According to Howard and his colleagues, recent research has demonstrated that brain lesions and DBS electrodes functionally connected to the SBC-RSC impair cognition—while other pieces of research have shown what appears to be the opposite effect in DBS for Alzheimer’s.
For the present study, researchers examined electrode locations and cognitive outcomes in a total of 33 patients who received subthalamic nucleus DBS for Parkinson’s and 46 patients who received fornix DBS for Alzheimer’s. They then related the observed DBS sites to the lesion-based, a-priori SBC-RSC region of interest, and tested whether connectivity between DBS sites and the SBC-RSC was significantly correlated with memory outcomes, as well as whether the difference between Parkinson’s and Alzheimer’s was significant. The researchers also used whole-brain mapping to assess if both diseases were driven by the same region in the SBC-RSC and, finally, investigated the influence of patient age upon outcomes.
As reported by Howard at AAN 2024, connectivity to the SBC-RSC was simultaneously correlated with cognitive decline in Parkinson’s disease patients and cognitive improvement in Alzheimer’s disease patients. He and his colleagues also found that the difference between the two diseases was statistically significant. In addition to this, a data-driven, whole-brain analysis of connections correlating with cognitive decline revealed that both diseases were driven by the same SBC-RSC region.
Among other key findings was the fact that—as per subsequent regression analyses—both groups were found to have demonstrated significant interactions with patient age. High SBC-RSC connectivity was also associated with improved cognitive outcomes in older patients compared to impaired cognition in younger patients, while low SBC-RSC connectivity had the opposite effect on these age groups. Lastly, Howard relayed that further data-driven analysis identified the inflection point as occurring at 65 years of age in both Parkinson’s and Alzheimer’s.
Howard concluded by noting that the cognitive effects of DBS, in both of these diseases, are “unified” when considering connectivity to the SBC-RSC, and also patient age. He further stated that the “magnitude of impact” upon cognition primarily correlates with the degree of DBS connectivity to the SBC-RSC—but whether DBS impairs or improves cognition is dependent on patient age.
Following this presentation at AAN, Howard spoke to NeuroNews to relay that he and his colleagues are now actively working to expand upon these findings. They recently collected additional data from retrospective cohorts and have since validated their results, with their final planned step being to translate these findings into neuroanatomical targets to guide DBS electrode implantation by neurosurgeons, and electrode programming by neurologists.
