Topological descriptors of foot clearance gait dynamics improve differential diagnosis of Parkinsonism

Participant-disjoint cross-validation prevents direct participant overlap, but it may still produce optimistic estimates when acquisition site and diagnosis are structurally dependent. We examined Parkinson's disease classification using 159 pressure-walkway summary features from 133 WearGait-PD participants, including 65 participants with Parkinson's disease and 68 controls. The cohort was non-factorial: two sites contained only one diagnostic group, whereas VA-Seattle was the only site containing both groups. In repeated participant-level nested cross-validation, site alone achieved an area under the receiver operating characteristic curve (AUC) of 0.955 plus or minus 0.003, exceeding the gait-feature model (0.882 plus or minus 0.014). Under the evaluated logistic-regression pipelines, adding gait features to site, age, and sex produced no measurable improvement in pooled discrimination. More site-controlled evaluations produced lower and imprecise estimates: VA-Seattle same-site AUC was 0.668 (95% bootstrap confidence interval 0.477 to 0.836), and the JHOC + Bayview-to-VA-Seattle transport stress test achieved 0.576 (0.375 to 0.770). Supporting within-diagnosis site-prediction and site-conditioned permutation analyses showed that the gait representation retained substantial acquisition-site structure. These findings indicate that participant-disjoint pooled validation did not isolate disease-related discrimination from site-associated variation. They encourage careful examination of site-label dependence and, where possible, support for pooled results through within-site or independent validation before broader claims are made about generalization across institutions.

Parkinson's disease alters gait and bilateral coordination, but machine-learning performance also depends on how continuous gait signals are represented. This study investigates whether preserving anterior-posterior center-of-pressure (AP-COP) information at fixed locations across normalized stance provides a compact and informative representation of plantar-force gait signals. Bilateral vertical ground reaction force recordings from 165 participants in the Gait in Parkinson's Disease Database were evaluated using repeated fully nested participant-level cross-validation. We propose AP-COP10, comprising AP-COP position and bilateral asymmetry across five stance windows. AP-COP10 achieved an AUC of 0.894 and outperformed three harmonized literature-derived COP representations under the same evaluation pipeline. The complementary 25 non-AP-COP descriptors alone achieved an AUC of 0.856, while the complete 35-feature representation achieved 0.908. Removing AP-COP10 from the complete representation produced a statistically supported loss in discrimination, whereas adding the complementary descriptors to AP-COP10 yielded only a small, unsupported improvement. Feature competition indicated that the most informative stance-indexed descriptors were concentrated in early and early-mid stance, while source-study holdout and sensor-perturbation analyses supported the robustness of the representation. These findings indicate that stance-indexed AP-COP retains discriminative information that is not readily recovered by broader engineered gait descriptors, supporting compact and interpretable representations for machine-learning analysis of pathological gait.

Dynamic Time Warping (DTW) is the dominant approach for measuring similarity between time series, yet standard practice discards the optimal warping path after computing a single distance value, losing local alignment information most relevant to clinical diagnosis. We introduce DiaSeg, a framework that extracts diagonal segments from DTW paths with controlled breaks, characterizing each segment by five geometric features (effective length, interruption count, cost variation, temporal position, and path context), and enabling unsupervised pattern discovery without domain-specific feature engineering. Validated on 91 subjects across six clinical conditions (healthy aging, Parkinson's, Huntington's, ALS, brain tumor, and stroke), three findings emerge. First, diagonal segments form consistent unsupervised patterns (silhouette 0.33) aligned with biomechanical phase annotations, with label-based validation confirming near-perfect separation of healthy and pathological gait (ARI up to 0.986). Second, segments discriminate pathology at 69% (supervised) and 75% (patient-level clustering), with pathology manifesting through distributional shifts in segment length; combining segment and cycle-level features further improves classification to 91.7%. Third, while cycle-based methods achieve higher accuracy (91%), diagonal segments provide phase-specific interpretability unavailable in global representations, localizing where coordination breaks down within the gait cycle. DiaSeg thus transforms DTW from a black-box distance into a source of interpretable temporal features for neurodegenerative disease assessment.