Orthostatic Hypotension: A Prodromal Marker of Parkinson's Disease?

Abstract

Background Orthostatic hypotension is common in patients with Parkinson's disease (PD). However, it remains unknown whether orthostatic hypotension is a marker of prodromal PD or more advanced disease. The objectives of this study were to assess whether orthostatic hypotension is a prodromal marker of PD in the general population. Methods This study was embedded in the Rotterdam Study, a large prospective population‐based cohort in the Netherlands. We measured orthostatic hypotension in 6910 participants. First, we determined the relation between prevalent PD and orthostatic hypotension using logistic regression. Second, we followed PD‐free participants for the occurrence of PD until 2016 and studied the association between orthostatic hypotension and the risk of PD using Cox proportional hazards models. All models were adjusted for age and sex. Results At baseline, the mean age ± standard deviation of the study population was 69.0 ± 8.8 years, and 59.1% were women. Orthostatic hypotension was present in 1245 participants (19.8%), and 62 participants (1.0%) had PD at the time of orthostatic hypotension measurement. Participants with PD were significantly more likely to have orthostatic hypotension (odds ratio, 1.88; 95% confidence interval, 1.09–3.24). During a median (interquartile range) follow‐up of 16.1 years (8.5–22.7 years), 122 participants were diagnosed with incident PD. Orthostatic hypotension at baseline was not associated with an increased risk of PD (hazard ratio, 0.97; 95% confidence interval, 0.59–1.58). Conclusions Our study suggests that orthostatic hypotension is common in patients with PD, but that orthostatic hypotension is not associated with an increased risk of PD and thus is not a prodromal marker of PD in the general population. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Orthostatic Hypotension in Parkinson Disease

“…4 However, this field of research is not free from controversy as a recent prospective population‐based study failed to identify an association between neurogenic OH and an increased risk of developing PD. 5 Differences in study populations likely explain these contradictory findings. Patients diagnosed with PAF seen at specialized autonomic centers are more likely to be screened for other nonmotor features suggestive of a synucleinopathy (e.g., dream enactment behavior, anosmia, constipation, family history of PD) and may have more severe OH than in the general population.…”

Corneal confocal microscopy differentiates patients with Parkinson’s disease with and without autonomic involvement

“…Delayed gastric emptying can lead to impaired drug absorption with the “delayed ON” or even “no ON” phenomenon interfering with the therapeutic effect of dopaminergic medication, worsening motor function. Orthostatic hypotension can cause syncope and falls 16 and fall-related fractures, pneumonia, and even death. Some autonomic symptoms, such as constipation, can occur in the early stage of disease and may even precede the onset of motor symptoms by many years 16 , 17 .…”

“…Orthostatic hypotension can cause syncope and falls 16 and fall-related fractures, pneumonia, and even death. Some autonomic symptoms, such as constipation, can occur in the early stage of disease and may even precede the onset of motor symptoms by many years 16 , 17 . We speculate that both dopaminergic and adrenergic neurons in the nigrostriatal and peripheral nervous systems are lost progressively with the gradual worsening of motor and non-motor symptoms.…”

Probing the Pre-diagnostic Phase of Parkinson's Disease in Population-Based Studies

“…This difference in external validity might explain some common discrepancies in findings between clinical studies and population-based studies. As an illustration, while specialized clinics found a substantial increased likelihood for PD in people with neurogenic orthostatic hypotension (54,59,60), in the population-based Rotterdam study we previously found no significant association between neurogenic orthostatic hypotension and PD (61). The high external validity of population-based studies also offers several possibilities, for example to study the prevalence and trajectories of symptoms in pre-diagnostic PD, which is necessary to determine the predictive ability of these symptoms (8,31).…”