Dataset Information

Patients with Cognitive Impairment in Parkinson's Disease Benefit from Deep Brain Stimulation: A Case-Control Study.

ABSTRACT:

Background

Deep brain stimulation (DBS) for Parkinson's disease (PD) is generally contraindicated in persons with dementia but it is frequently performed in people with mild cognitive impairment or normal cognition, and current clinical guidelines are primarily based on these cohorts.

Objectives

To determine if moderately cognitive impaired individuals including those with mild dementia could meaningfully benefit from DBS in terms of motor and non-motor outcomes.

Methods

In this retrospective case-control study, we identified a cohort of 40 patients with PD who exhibited moderate (two or more standard deviations below normative scores) cognitive impairment (CI) during presurgical workup and compared their 1-year clinical outcomes to a cohort of 40 matched patients with normal cognition (NC). The surgery targeted subthalamus, pallidus or motor thalamus, in a unilateral, bilateral or staged approach.

Results

At preoperative baseline, the CI cohort had higher Unified Parkinson's Disease Rating Scale (UPDRS) subscores, but similar levodopa responsiveness compared to the NC cohort. The NC and CI cohorts demonstrated comparable degrees of postoperative improvement in the OFF-medication motor scores, motor fluctuations, and medication reduction. There was no difference in adverse event rates between the two cohorts. Outcomes in the CI cohort did not depend on the target, surgical staging, or impaired cognitive domain.

Conclusions

Moderately cognitively impaired patients with PD can experience meaningful motor benefit and medication reduction with DBS.

SUBMITTER: Block CK

PROVIDER: S-EPMC10026300 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Patients with Cognitive Impairment in Parkinson's Disease Benefit from Deep Brain Stimulation: A Case-Control Study.

Block Cady K CK Patel Margi M Risk Benjamin B BB Staikova Ekaterina E Loring David D Esper Christine D CD Scorr Laura L Higginbotham Lenora L Aia Pratibha P DeLong Mahlon R MR Wichmann Thomas T Factor Stewart A SA Au Yong Nicholas N Willie Jon T JT Boulis Nicholas M NM Gross Robert E RE Buetefisch Cathrin C Miocinovic Svjetlana S

Movement disorders clinical practice 20230130 3

<h4>Background</h4>Deep brain stimulation (DBS) for Parkinson's disease (PD) is generally contraindicated in persons with dementia but it is frequently performed in people with mild cognitive impairment or normal cognition, and current clinical guidelines are primarily based on these cohorts.<h4>Objectives</h4>To determine if moderately cognitive impaired individuals including those with mild dementia could meaningfully benefit from DBS in terms of motor and non-motor outcomes.<h4>Methods</h4>In ...[more]

PMID: 36949802

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Project description:Deep brain stimulation is an effective treatment for Parkinson's disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate deep brain stimulation settings. Here, we test whether connectivity between the stimulation site and other brain regions is associated with cognitive decline following deep brain stimulation. First, we studied a unique patient cohort with cognitive decline following subthalamic deep brain stimulation for Parkinson's disease (n = 10) where reprogramming relieved the side-effect without loss of motor benefit. Using resting state functional connectivity data from a large normative cohort (n = 1000), we computed connectivity between each stimulation site and the subiculum, an a priori brain region functionally connected to brain lesions causing memory impairment. Connectivity between deep brain stimulation sites and this same subiculum region was significantly associated with deep brain stimulation induced cognitive decline (P < 0.02). We next performed a data-driven analysis to identify connections most associated with deep brain stimulation induced cognitive decline. Deep brain stimulation sites causing cognitive decline (versus those that did not) were more connected to the anterior cingulate, caudate nucleus, hippocampus, and cognitive regions of the cerebellum (PFWE < 0.05). The spatial topography of this deep brain stimulation-based circuit for cognitive decline aligned with an a priori lesion-based circuit for memory impairment (P = 0.017). To begin translating these results into a clinical tool that might be used for deep brain stimulation programming, we generated a 'heat map' in which the intensity of each voxel reflects the connectivity to our cognitive decline circuit. We then validated this heat map using an independent dataset of Parkinson's disease patients in which cognitive performance was measured following subthalamic deep brain stimulation (n = 33). Intersection of deep brain stimulation sites with our heat map was correlated with changes in the Mattis dementia rating scale 1 year after lead implantation (r = 0.39; P = 0.028). Finally, to illustrate how this heat map might be used in clinical practice, we present a case that was flagged as 'high risk' for cognitive decline based on intersection of the patient's deep brain stimulation site with our heat map. This patient had indeed experienced cognitive decline and our heat map was used to select alternative deep brain stimulation parameters. At 14 days follow-up the patient's cognition improved without loss of motor benefit. These results lend insight into the mechanism of deep brain stimulation induced cognitive decline and suggest that connectivity-based heat maps may help identify patients at risk and who might benefit from deep brain stimulation reprogramming.

Project description:IntroductionSubthalamic Deep Brain Stimulation (STN-DBS) is a safe and well-established therapy for the management of motor symptoms refractory to best medical treatment in patients with Parkinson's disease (PD). Early intervention is discussed especially for Early-onset PD (EOPD) patients that present with an age of onset ≤ 45-50 years and see themselves often confronted with high psychosocial demands.MethodsWe retrospectively assessed the effect of STN-DBS at 12 months follow-up (12-MFU) in 46 EOPD-patients. Effects of stimulation were evaluated by comparison of disease-specific scores for motor and non-motor symptoms including impulsiveness, apathy, mood, quality of life (QoL), cognition before surgery and in the stimulation ON-state without medication. Further, change in levodopa equivalent dosage (LEDD) after surgery, DBS parameter, lead localization, adverse and serious adverse events as well as and possible additional clinical features were assessed.ResultsPD-associated gene mutations were found in 15% of our EOPD-cohort. At 12-MFU, mean motor scores had improved by 52.4 ± 17.6% in the STIM-ON/MED-OFF state compared to the MED-OFF state at baseline (p = 0.00; n = 42). These improvements were accompanied by a significant 59% LEDD reduction (p < 0.001), a significant 6.6 ± 16.1 points reduction of impulsivity (p = 0.02; n = 35) and a significant 30 ± 50% improvement of QoL (p = 0.01). At 12-MFU, 9 patients still worked full- and 6 part-time. Additionally documented motor and/or neuropsychiatric features decreased from n = 41 at baseline to n = 14 at 12-MFU.ConclusionThe present study-results demonstrate that EOPD patients with and without known genetic background benefit from STN-DBS with significant improvement in motor as well as non-motor symptoms. In line with this, patients experienced a meaningful reduction of additional neuropsychiatric features. Physicians as well as patients have an utmost interest in possible predictors for the putative DBS outcome in a cohort with such a highly complex clinical profile. Longitudinal monitoring of DBS-EOPD-patients over long-term intervals with standardized comprehensive clinical assessment, accurate phenotypic characterization and documentation of clinical outcomes might help to gain insights into disease etiology, to contextualize genomic information and to identify predictors of optimal DBS candidates as well as those in danger of deterioration and/or non-response in the future.

Dataset Information

Patients with Cognitive Impairment in Parkinson's Disease Benefit from Deep Brain Stimulation: A Case-Control Study.

Background

Objectives

Methods

Results

Conclusions

Publications

Patients with Cognitive Impairment in Parkinson's Disease Benefit from Deep Brain Stimulation: A Case-Control Study.

Similar Datasets

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