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Data-Driven Models for Objective Grading Improvement of Parkinson's Disease.

ABSTRACT: Parkinson's disease (PD) is a progressive disorder of the central nervous system that causes motor dysfunctions in affected patients. Objective assessment of symptoms can support neurologists in fine evaluations, improving patients' quality of care. Herein, this study aimed to develop data-driven models based on regression algorithms to investigate the potential of kinematic features to predict PD severity levels. Sixty-four patients with PD (PwPD) and 50 healthy subjects of control (HC) were asked to perform 13 motor tasks from the MDS-UPDRS III while wearing wearable inertial sensors. Simultaneously, the clinician provided the evaluation of the tasks based on the MDS-UPDRS scores. One hundred-ninety kinematic features were extracted from the inertial motor data. Data processing and statistical analysis identified a set of parameters able to distinguish between HC and PwPD. Then, multiple feature selection methods allowed selecting the best subset of parameters for obtaining the greatest accuracy when used as input for several predicting regression algorithms. The maximum correlation coefficient, equal to 0.814, was obtained with the adaptive neuro-fuzzy inference system (ANFIS). Therefore, this predictive model could be useful as a decision support system for a reliable objective assessment of PD severity levels based on motion performance, improving patients monitoring over time.

SUBMITTER: Butt AH

PROVIDER: S-EPMC7723941 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Data-Driven Models for Objective Grading Improvement of Parkinson's Disease.

Butt Abdul Haleem AH Rovini Erika E Fujita Hamido H Maremmani Carlo C Cavallo Filippo F

Annals of biomedical engineering 20201001 12

Parkinson's disease (PD) is a progressive disorder of the central nervous system that causes motor dysfunctions in affected patients. Objective assessment of symptoms can support neurologists in fine evaluations, improving patients' quality of care. Herein, this study aimed to develop data-driven models based on regression algorithms to investigate the potential of kinematic features to predict PD severity levels. Sixty-four patients with PD (PwPD) and 50 healthy subjects of control (HC) were as ...[more]

PMID: 33006005

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Project description:Objective.Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) but its success depends on a time-consuming process of trial-and-error to identify the optimal stimulation settings for each individual patient. Data-driven optimization algorithms have been proposed to efficiently find the stimulation setting that maximizes a quantitative biomarker of symptom relief. However, these algorithms cannot efficiently take into account stimulation settings that may control symptoms but also cause side effects. Here we demonstrate how multi-objective data-driven optimization can be used to find the optimal trade-off between maximizing symptom relief and minimizing side effects.Approach.Cortical and motor evoked potential data collected from PD patients during intraoperative stimulation of the subthalamic nucleus were used to construct a framework for designing and prototyping data-driven multi-objective optimization algorithms. Using this framework, we explored how these techniques can be applied clinically, and characterized the design features critical for solving this optimization problem. Our two optimization objectives were to maximize cortical evoked potentials, a putative biomarker of therapeutic benefit, and to minimize motor potentials, a biomarker of motor side effects.Main Results.Using thisin silicodesign framework, we demonstrated how the optimal trade-off between two objectives can substantially reduce the stimulation parameter space by 61 ± 19%. The best algorithm for identifying the optimal trade-off between the two objectives was a Bayesian optimization approach with an area under the receiver operating characteristic curve of up to 0.94 ± 0.02, which was possible with the use of a surrogate model and a well-tuned acquisition function to efficiently select which stimulation settings to sample.Significance.These findings show that multi-objective optimization is a promising approach for identifying the optimal trade-off between symptom relief and side effects in DBS. Moreover, these approaches can be readily extended to newly discovered biomarkers, adapted to DBS for disorders beyond PD, and can scale with the development of more complex DBS devices.

Project description:See Li and Donohue (doi:10.1093/brain/awy089) for a scientific commentary on this article.Dominantly-inherited Alzheimer's disease is widely hoped to hold the key to developing interventions for sporadic late onset Alzheimer's disease. We use emerging techniques in generative data-driven disease progression modelling to characterize dominantly-inherited Alzheimer's disease progression with unprecedented resolution, and without relying upon familial estimates of years until symptom onset. We retrospectively analysed biomarker data from the sixth data freeze of the Dominantly Inherited Alzheimer Network observational study, including measures of amyloid proteins and neurofibrillary tangles in the brain, regional brain volumes and cortical thicknesses, brain glucose hypometabolism, and cognitive performance from the Mini-Mental State Examination (all adjusted for age, years of education, sex, and head size, as appropriate). Data included 338 participants with known mutation status (211 mutation carriers in three subtypes: 163 PSEN1, 17 PSEN2, and 31 APP) and a baseline visit (age 19-66; up to four visits each, 1.1 ± 1.9 years in duration; spanning 30 years before, to 21 years after, parental age of symptom onset). We used an event-based model to estimate sequences of biomarker changes from baseline data across disease subtypes (mutation groups), and a differential equation model to estimate biomarker trajectories from longitudinal data (up to 66 mutation carriers, all subtypes combined). The two models concur that biomarker abnormality proceeds as follows: amyloid deposition in cortical then subcortical regions (∼24 ± 11 years before onset); phosphorylated tau (17 ± 8 years), tau and amyloid-β changes in cerebrospinal fluid; neurodegeneration first in the putamen and nucleus accumbens (up to 6 ± 2 years); then cognitive decline (7 ± 6 years), cerebral hypometabolism (4 ± 4 years), and further regional neurodegeneration. Our models predicted symptom onset more accurately than predictions that used familial estimates: root mean squared error of 1.35 years versus 5.54 years. The models reveal hidden detail on dominantly-inherited Alzheimer's disease progression, as well as providing data-driven systems for fine-grained patient staging and prediction of symptom onset with great potential utility in clinical trials.

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Project description:Parkinson's disease (PD) is associated with diverse clinical manifestations including motor and non-motor signs and symptoms, and emerging biomarkers. We aimed to reveal the heterogeneity of PD to define subtypes and their progression rates using an automated deep learning algorithm on the top of longitudinal clinical records. This study utilizes the data collected from the Parkinson's Progression Markers Initiative (PPMI), which is a longitudinal cohort study of patients with newly diagnosed Parkinson's disease. Clinical information including motor and non-motor assessments, biospecimen examinations, and neuroimaging results were used for identification of PD subtypes. A deep learning algorithm, Long-Short Term Memory (LSTM), was used to represent each patient as a multi-dimensional time series for subtype identification. Both visualization and statistical analysis were performed for analyzing the obtained PD subtypes. As a result, 466 patients with idiopathic PD were investigated and three subtypes were identified. Subtype I (Mild Baseline, Moderate Motor Progression) is comprised of 43.1% of the participants, with average age 58.79 ± 9.53 years, and was characterized by moderate functional decay in motor ability but stable cognitive ability. Subtype II (Moderate Baseline, Mild Progression) is comprised of 22.9% of the participants, with average age 61.93 ± 6.56 years, and was characterized by mild functional decay in both motor and non-motor symptoms. Subtype III (Severe Baseline, Rapid Progression) is comprised 33.9% of the patients, with average age 65.32 ± 8.86 years, and was characterized by rapid progression of both motor and non-motor symptoms. These subtypes suggest that when comprehensive clinical and biomarker data are incorporated into a deep learning algorithm, the disease progression rates do not necessarily associate with baseline severities, and the progression rate of non-motor symptoms is not necessarily correlated with the progression rate of motor symptoms.

Dataset Information

Data-Driven Models for Objective Grading Improvement of Parkinson's Disease.

Publications

Data-Driven Models for Objective Grading Improvement of Parkinson's Disease.

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