LAUSR

With great interest we read the article recently published by Dadar and colleagues in Movement Disorders Clinical Practice. They report that in patients with early untreated de novo Parkinson’s disease (PD), the interplay between dysautonomia and the burden of white matter hyperintensities (WMH) results in pronounced and accelerated cognitive decline. Although their results are of critical significance to help understand pathophysiological changes underlying cognitive decline and to address dysautonomia as a potential therapeutic target, we consider that there is 1 situation that has remained understudied in PD: cerebral vasomotor reactivity (CVR). CVR is a measure of cerebral dynamic autoregulation: the capacity to maintain constant cerebral blood flow despite sudden or abrupt changes in perfusion, such as orthostatic hypotension or supine hypertension. In PD, studies have reported impaired CVR in 34% to 70% of patients (depending on the definition used) and unrelated to the presence of orthostatic hypotension, age, gender, disease duration, severity, or levodopa use. However, it has been suggested that chronic changes in perfusion (manifested as orthostatic hypotension or supine hypertension) exceed the autoregulatory capacity of the cerebral dynamic autoregulation, leading to abnormal adaptative responses that might present as WMH. Thus emphasizing the need of longitudinal studies evaluating the effect of CVR and WMH in cognition, along with its association to clinical manifestations of PD. Available studies to date have not resolved whether impairment of CVR is intrinsic to PD or is part of a compensatory mechanism for autonomic failure.. Involvement of neuroanatomical substrates behind intrinsic neurogenic mechanisms that regulate CVR could explain its impairment in PD because some of these structures are also involved in the pathophysiology of PD and other synucleinopathies. We believe that patients with PD might exhibit an excessive vulnerability to injury during increased demands on the cerebral vasculature—such as orthostatic hypotension or supine hypertension—attributed to an impaired functional reserve or an abnormal compensatory mechanism of cerebral dynamic autoregulation. Further studies evaluating CVR in PD are warranted to confirm its association with WMH, cognition, and dysautonomia and to provide a more comprehensive understanding of the mechanisms underlying cognitive decline in PD.