Dataset Information

Nomogram to Predict Cognitive State Improvement after Deep Brain Stimulation for Parkinson's Disease.

ABSTRACT:

Purpose

Parkinson's disease (PD) is a common neurodegenerative disease, for which cognitive impairment is a non-motor symptom (NMS). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for PD. This study established a nomogram to predict cognitive improvement rate after STN-DBS in PD patients.

Methods

We retrospectively analyzed 103 PD patients who underwent STN-DBS. Patients were followed up to measure improvement in MoCA scores one year after surgery. Univariate and multivariate logistic regression analyses were used to identify factors affecting improvement in cognitive status. A nomogram was developed to predict this factor. The discrimination and fitting performance were evaluated by receiver operating characteristics (ROC) analysis, calibration diagram, and decision curve analysis (DCA).

Results

Among 103 patients, the mean improvement rate of the MoCA score was 37.3% and the median improvement rate was 27.3%, of which 64% improved cognition, 27% worsened cognition, and 8.7% remained unchanged. Logistic multivariate regression analysis showed that years of education, UPDRSIII drug use, MoCA Preop, and MMSE Preop scores were independent factors affecting the cognitive improvement rate. A nomogram model was subsequently developed. The C-index of the nomogram was 0.98 (95%CI, 0.97-1.00), and the area under the ROC was 0.98 (95%CI 0.97-1.00). The calibration plot and DCA demonstrated the goodness-of-fit between nomogram predictions and actual observations.

Conclusion

Our nomogram could effectively predict the possibility of achieving good cognitive improvement one year after STN-DBS in patients with PD. This model has value in judging the expected cognitive improvement of patients with PD undergoing STN-DBS.

SUBMITTER: Chang B

PROVIDER: S-EPMC9220903 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Nomogram to Predict Cognitive State Improvement after Deep Brain Stimulation for Parkinson's Disease.

Chang Bowen B Ni Chen C Zhang Weiwen W Mei Jiaming J Xiong Chi C Chen Peng P Jiang Manli M Niu Chaoshi C

Brain sciences 20220609 6

<h4>Purpose</h4>Parkinson's disease (PD) is a common neurodegenerative disease, for which cognitive impairment is a non-motor symptom (NMS). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for PD. This study established a nomogram to predict cognitive improvement rate after STN-DBS in PD patients.<h4>Methods</h4>We retrospectively analyzed 103 PD patients who underwent STN-DBS. Patients were followed up to measure improvement in MoCA scores one year after ...[more]

PMID: 35741644

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Project description:BackgroundParkinson's disease is a common neurodegenerative disease, with depression being a common non-motor symptom. Bilateral subthalamic nucleus deep brain stimulation is an effective method for the treatment of Parkinson's disease. Thus, this study aimed to establish a nomogram of the possibility of achieving a better depression improvement rate after subthalamic nucleus deep brain stimulation in patients with Parkinson's disease.MethodsWe retrospectively analyzed 103 patients with Parkinson's disease who underwent subthalamic nucleus deep brain stimulation and were followed up for the improvement of their Hamilton Depression scale scores 1 year postoperatively. Univariate and multivariate logistic regression analyses were used to select factors affecting the improvement rate of depression. A nomogram was then developed to predict the possibility of achieving better depression improvement. Furthermore, the discrimination and fitting performance was evaluated using a calibration diagram, receiver operating characteristics, and decision curve analysis.ResultsThe mean and median improvement rates of Hamilton Depression scores were 13.1 and 33.3%, respectively. Among the 103 patients, 70.8% had an improved depression, 23.3% had a worsened depression, and 5.8% remained unchanged. Logistic multivariate regression analysis showed that age, preoperative Parkinson's Disease Questionnaire, Hamilton Anxiety, and Hamilton Depression scores were independent factors for the possibility of achieving a better depression improvement rate. Based on these results, a nomogram model was developed. The nomogram had a C-index of 0.78 (95% confidence interval: 0.69-0.87) and an area under the receiver operating characteristics of 0.78 (95% confidence interval: 0.69-0.87). The calibration plot and decision curve analysis further demonstrated goodness-of-fit between the nomogram predictions and actual observations.ConclusionWe developed a nomogram to predict the possibility of achieving good depression improvement 1 year after subthalamic nucleus deep brain stimulation in patients with Parkinson's disease, which showed a certain value in judging the expected depression improvement of these patients.

Project description:Effective target regions for deep brain stimulation (DBS) in Parkinson's disease (PD) have been well characterized. We sought to study whether the measured Cartesian coordinates of an implanted DBS lead are predictive of motor outcome(s). We tested the hypothesis that the position and trajectory of the DBS lead relative to the mid-commissural point (MCP) are significant predictors of clinical outcomes. We expected that due to neuroanatomical variation among individuals, a simple measure of the position of the DBS lead relative to MCP (commonly used in clinical practice) may not be a reliable predictor of clinical outcomes when utilized alone.55 PD subjects implanted with subthalamic nucleus (STN) DBS and 41 subjects implanted with globus pallidus internus (GPi) DBS were included. Lead locations in AC-PC space (x, y, z coordinates of the active contact and sagittal and coronal entry angles) measured on high-resolution CT-MRI fused images, and motor outcomes (Unified Parkinson's Disease Rating Scale) were analyzed to confirm or refute a correlation between coordinate-based lead locations and DBS motor outcomes.Coordinate-based lead locations were not a significant predictor of change in UPDRS III motor scores when comparing pre- versus post-operative values. The only potentially significant individual predictor of change in UPDRS motor scores was the antero-posterior coordinate of the GPi lead (more anterior lead locations resulted in a worse outcome), but this was only a statistical trend (p<.082).The results of the study showed that a simple measure of the position of the DBS lead relative to the MCP is not significantly correlated with PD motor outcomes, presumably because this method fails to account for individual neuroanatomical variability. However, there is broad agreement that motor outcomes depend strongly on lead location. The results suggest the need for more detailed identification of stimulation location relative to anatomical targets.

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:Subthalamic nucleus deep brain stimulation is an effective treatment for advanced Parkinson's disease; however, its therapeutic mechanism is unclear. Previous modelling of functional MRI data has suggested that deep brain stimulation has modulatory effects on a number of basal ganglia pathways. This work uses an enhanced data collection protocol to collect rare functional MRI data in patients with subthalamic nucleus deep brain stimulation. Eleven patients with Parkinson's disease and subthalamic nucleus deep brain stimulation underwent functional MRI at rest and during a movement task; once with active deep brain stimulation, and once with deep brain stimulation switched off. Dynamic causal modelling and Bayesian model selection were first used to compare a series of plausible biophysical models of the cortico-basal ganglia circuit that could explain the functional MRI activity at rest in an attempt to reproduce and extend the findings from our previous work. General linear modelling of the movement task functional MRI data revealed deep brain stimulation-associated signal increases in the primary motor and cerebellar cortices. Given the significance of the cerebellum in voluntary movement, we then built a more complete model of the motor system by including cerebellar-basal ganglia interactions, and compared the modulatory effects deep brain stimulation had on different circuit components during the movement task and again using the resting state data. Consistent with previous results from our independent cohort, model comparison found that the rest data were best explained by deep brain stimulation-induced increased (effective) connectivity of the cortico-striatal, thalamo-cortical and direct pathway and reduced coupling of subthalamic nucleus afferent and efferent connections. No changes in cerebellar connectivity were identified at rest. In contrast, during the movement task, there was functional recruitment of subcortical-cerebellar pathways, which were additionally modulated by deep brain stimulation, as well as modulation of local (intrinsic) cortical and cerebellar circuits. This work provides in vivo evidence for the modulatory effects of subthalamic nucleus deep brain stimulation on effective connectivity within the cortico-basal ganglia loops at rest, as well as further modulations in the cortico-cerebellar motor system during voluntary movement. We propose that deep brain stimulation has both behaviour-independent effects on basal ganglia connectivity, as well as behaviour-dependent modulatory effects.

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

Nomogram to Predict Cognitive State Improvement after Deep Brain Stimulation for Parkinson's Disease.

Purpose

Methods

Results

Conclusion

Publications

Nomogram to Predict Cognitive State Improvement after Deep Brain Stimulation for Parkinson's Disease.

Similar Datasets

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