Clinical heterogeneity of Pisa syndrome across Lewy body disorders: a multicenter comparison of Parkinson's disease and dementia with Lewy bodies.

BACKGROUND

Pisa syndrome (PS) is well recognized in Parkinson's disease (PD) but has been less studied in dementia with Lewy bodies (DLB), and direct comparisons are scarce. The aim of this study is to compare the clinical expression of PS across PD and DLB.

METHODS

In this multicenter cross-sectional study, patients were classified as PD without PS (n = 50), PD with PS (n = 41), DLB without PS (n = 45), or DLB with PS (n = 35). Standardized assessments covered cognition, neuropsychiatric symptoms, caregiver burden, motor severity, gait, falls, daily function. Two-way models, disease-specific logistic regression, and mediation analyses were performed.

RESULTS

In both disorders, PS was associated with longer disease duration, worse daily functioning, and more recurrent falls. Significant disease × PS interactions were observed across cognitive, neuropsychiatric, gait, and fall outcomes. DLB-PS carried the heaviest cognitive and neuropsychiatric burden, whereas PD-PS showed the greatest motor and gait impairment. In PD, PS was independently associated with disease duration, MDS-UPDRS-III score, gait symmetry, and stride length. In DLB, PS was independently associated with lower attention and visuospatial/executive scores, greater hallucination severity, and a higher CDR stage. Attention/visuospatial dysfunction partly mediated the association between PS and recurrent falls in DLB, whereas gait asymmetry/stride impairment partly mediated the same association in PD.

CONCLUSION

PS is not a uniform phenotype across Lewy body disorders. Our findings suggest that it behaves relatively more like a cognition-neuropsychiatry-associated axial syndrome in DLB, whereas in PD, it shows stronger associations with motor and gait features. The effect sizes are modest, indicating that PS is a multifactorial clinical sign rather than a strong predictor of any single domain.