Orthostatic blood pressure trajectories characterize heterogeneous disease progression in Parkinson's disease.

Two distinct latent class trajectories of orthostatic systolic blood pressure change (ΔSBP) were identified in PD patients: a low-stable trajectory and an increasing trajectory.

• A total of 1,081 PD patients were included from two independent cohorts.
• Latent class trajectory modeling was applied to delineate longitudinal ΔSBP trajectories.
• The two classes were labeled 'low-stable' and 'increasing' based on the pattern of orthostatic SBP change over time.

Patients in the increasing ΔSBP trajectory exhibited a higher risk of developing cognitive impairment compared to those in the low-stable trajectory.

• Cox proportional hazards models were used to evaluate associations between ΔSBP trajectories and cognitive impairment onset.
• The analysis was conducted across two independent cohorts to validate findings.
• The increasing trajectory group showed faster decline in visuospatial, attentional, and executive functions.

Patients in the increasing ΔSBP trajectory showed more severe motor symptoms and rapid eye movement sleep behavior disorder compared to the low-stable trajectory group.

• Linear mixed-effects models were used to evaluate associations between ΔSBP trajectories and motor progression.
• REM sleep behavior disorder was more severe in the increasing trajectory class.
• Motor symptom severity was assessed longitudinally across the two cohorts.

The increasing ΔSBP trajectory was associated with accelerated progression of autonomic dysfunction and impairment in activities of daily living.

• Autonomic dysfunction progression was faster in the increasing ΔSBP trajectory class.
• Activities of daily living impairment was also more pronounced in the increasing trajectory group.
• Both Cox proportional hazards models and linear mixed-effects models were employed to assess these associations.

Prior studies on orthostatic hypotension and PD progression have largely relied on single baseline assessments, overlooking longitudinal fluctuations in orthostatic blood pressure changes.

• This limitation motivated the use of latent class trajectory modeling to capture longitudinal ΔSBP patterns.
• The study included 1,081 PD patients from two independent cohorts to address this gap.
• Longitudinal orthostatic blood pressure patterns are proposed as a clinically relevant dimension of disease heterogeneity.