Objective: Deep brain stimulation (DBS) is a highly effective treatment for Parkinson’s disease (PD) motor symptoms; however, its benefits can be overshadowed by side effects such as cognitive decline. Since there are currently no methods to predict which patients will experience the side effects of cognitive decline, it is difficult to identify patients at risk and know how to select appropriate DBS settings to avoid this distressing side effect.

Background: Brain lesions functionally connected to the subiculum, part of the hippocampal formation that plays a key role in mediating hippocampal-cortical interaction, cause cognitive impairment. Previous data from our lab in a small number of patients has shown that connectivity between the subthalamic nucleus (STN)-DBS site and the subiculum is associated with DBS-induced cognitive decline. Moreover, higher connectivity between the DBS site and subiculum correlated with changes in cognition as measured by the Mattis dementia rating scale (MDRS). Further, this connectivity could be assessed without specialized connectivity data from the patients by using resting state functional connectivity data from a large normative cohort (n=1000).

Method: We assessed whether connectivity between the STN stimulation site and the subiculum is associated with cognitive decline in PD patients who underwent DBS at the Brigham and Women’s Hospital (BWH). Using our established methods, we computed connectivity between each patient’s stimulation site and the subiculum and identified PD patients at high risk for cognitive decline after DBS. We first assessed patients’ cognitive function via a questionnaire and, for those who opted in, with a complementary zoom-based cognitive assessment.

Results: The computational prediction was confirmed with the cognitive questionnaire and a complementary zoom-based cognitive assessment, depicting that a higher level of connectivity correlated with higher scores in the cognitive questionnaire and worse performance in the zoom-based cognitive assessment.

Conclusion: These results provide a non-invasive, inexpensive approach to determine the risk of post-DBS cognitive decline and lay the groundwork for a prospective DBS reprogramming trial in PD patients who show cognitive decline following STN-DBS. Ultimately, we hope this body of research will contribute to improving PD treatment for cognitive and motor symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/predictor-of-post-deep-brain-stimulation-cognitive-decline-in-parkinsons-disease-patients/