Parkinson's Disease

Drug recommendation requires a deep understanding of individual patient context, especially for complex conditions like Parkinson's disease. While LLMs possess broad medical knowledge, they fail to capture the subtle nuances of actual prescribing patterns. Existing RAG methods also struggle with these complexities because guideline-based retrieval remains too generic and similar-patient retrieval often replicates majority patterns without accounting for the unique clinical nuances of individual patients. To bridge this gap, we propose PACE-RAG (Patient-Aware Contextual and Evidence-Constrained RAG). Rather than directly copying frequent medications from retrieved patients, PACE-RAG personalizes recommendations by first extracting patient-specific clinical features, retrieving cases around these features, and then refining the final prescription using the patient's current symptoms, active medication history, and focus-specific prescribing tendencies. By analyzing treatment patterns tailored to specific clinical features, PACE-RAG generates patient-specific medication recommendations along with an explainable clinical summary. PACE-RAG achieved the strongest performance among the evaluated inference-only LLM-based methods, reaching F1 scores of 80.84% and 47.22% on the Parkinson's disease and MIMIC-IV cohorts, respectively. Our code is available at: https://github.com/ChaeYoungHuh/PACE-RAG.

Automatic detection of Parkinson's disease (PD) from speech is a promising non-invasive diagnostic tool, but it raises significant privacy concerns. Speaker anonymization mitigates these risks, but it may suppress the pathological information necessary for PD detection. We assess the trade-off between privacy and PD detection for two anonymizers (STT-TTS and kNN-VC) using two Spanish datasets. STT-TTS provides better privacy but severely degrades PD detection by eradicating prosodic information. kNN-VC preserves macro-prosodic features such as duration and F0 contours, achieving F1 scores only 3-7% lower than original baselines, demonstrating that privacy-preserving PD detection is viable when using appropriate anonymization. Finally, an acoustic distortion analysis characterizes specific weaknesses in kNN-VC, offering insights for designing anonymizers that better preserve PD information.

Differential diagnosis among parkinsonian syndromes remains a clinical challenge due to overlapping motor symptoms and subtle gait abnormalities. Accurate differentiation is crucial for treatment planning and prognosis. While gait analysis is a well established approach for assessing motor impairments, conventional methods often overlook hidden nonlinear and structural features embedded in foot clearance patterns. We evaluated Topological Data Analysis (TDA) as a complementary tool for Parkinsonism classification using foot clearance time series. Persistent homology produced Betti curves, persistence landscapes, and silhouettes, which were used as features for a Random Forest classifier. The dataset comprised 15 controls (CO), 15 idiopathic Parkinson's disease (IPD), and 14 vascular Parkinsonism (VaP). Models were assessed with leave-one-out cross-validation (LOOCV). Betti-curve descriptors consistently yielded the strongest results. For IPD vs VaP, foot clearance variables minimum toe clearance, maximum toe late swing, and maximum heel clearance achieved 83% accuracy and AUC=0.89 under LOOCV in the medicated (On) state. Performance improved in the On state and further when both Off and On states were considered, indicating sensitivity of the topological features to levodopa related gait changes. These findings support integrating TDA with machine learning to improve clinical gait analysis and aid differential diagnosis across parkinsonian disorders.

Freezing of Gait (FOG) is a debilitating motor symptom commonly experienced by individuals with Parkinson's Disease (PD) which often leads to falls and reduced mobility. Timely and accurate prediction of FOG episodes is essential for enabling proactive interventions through assistive technologies. This study presents a reinforcement learning-based framework designed to identify optimal pre-FOG onset points, thereby extending the prediction horizon for anticipatory cueing systems. The model implements a Double Deep Q-Network (DDQN) architecture enhanced with Prioritized Experience Replay (PER) allowing the agent to focus learning on high-impact experiences and refine its policy. Trained over 9000 episodes with a reward shaping strategy that promotes cautious decision-making, the agent demonstrated robust performance in both subject-dependent and subject-independent evaluations. The model achieved a prediction horizon of up to 8.72 seconds prior to FOG onset in subject-independent scenarios and 7.89 seconds in subject-dependent settings. These results highlight the model's potential for integration into wearable assistive devices, offering timely and personalized interventions to mitigate FOG in PD patients.

Discrepancies between clinical diagnoses and omics profiles within a characterized cohort may reflect misdiagnosis, hidden subgroups or prodromal disease states. We propose MLASDO, a tool to detect and characterize such discrepancies before downstream analyses. MLASDO (1) detects outliers using two unsupervised methods, thereby flagging potential poor-quality samples; and (2) identifies and characterizes anomalous samples (ASs), i.e., individuals whose molecular profile resembles the opposite clinical class. We applied MLASDO to the Parkinson's Progression Markers Initiative (PPMI) and Parkinson's Disease Biomarkers Program (PDBP) Parkinson's disease (PD) cohorts. In PPMI, it detected 26 outliers and 12 ASs: 5 anomalous healthy controls (AHCs) and 7 anomalous PD cases (APDs). AHCs exhibited higher cerebrospinal fluid (CSF) A\b{eta}1-42 levels than controls (P < 0.0396), suggesting resistance to cognitive decline. AHC-specific genes were enriched for the MAPK pathway (P<0.0145), implicated in PD pathogenesis. One AHC later received a different neurological disorder, three months after enrollment. In PDBP, it identified 10 outliers and 8 ASs: 2 AHCs and 6 APDs. One AHC exhibited 24 clinical features consistent with a PD-like phenotype, including severe motor impairment. Results are compiled in an interactive report for inspection and querying, highlighting clinically meaningful individuals otherwise overlooked in conventional analyses.

Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD) and a common cause of injurious falls. Recent advances in wearable-based human activity recognition (HAR) have enabled FOG detection, but bias and fairness in these models remain understudied. Bias is defined as a systematic error leading to unequal outcomes, while fairness refers to consistent performance across subject groups. Biased models could systematically underserve patients with specific FOG phenotypes or demographics, widening care disparities. We evaluated the bias and fairness of state-of-the-art HAR models for FOG detection across FOG phenotypes and patient demographics using 4 public wearable datasets (145 subjects and 59.8 hours of recording) with multiple on-body sensor locations and temporal annotations on FOG episodes across various behavioral test protocols. Four mitigation approaches were assessed: conventional methods (threshold optimization and adversarial debiasing) and two transfer learning-based approaches (multi-site transfer and fine-tuning pre-trained models). Fairness was primarily quantified using the demographic parity ratio (DPR) and the equalized odds ratio (EOR). HAR models exhibited substantial bias (DPR & EOR < 0.8) across age, sex, disease duration, and critically, FOG phenotype. This phenotype-specific bias is particularly concerning as tremulous and akinetic FOG may require different clinical management. Conventional methods failed: threshold optimization (DPR=-0.126, EOR=+0.063) and adversarial debiasing (DPR=-0.008, EOR=-0.001). In contrast, multi-site transfer learning improved fairness (DPR=+0.037, p<0.01; EOR=+0.045, p<0.01) and performance (F1-score=+0.020, p<0.05), though neither metric reached 0.8. Transfer learning across diverse datasets may partially mitigate these disparities, helping wearable-based FOG monitoring benefit all individuals with PD.