Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders

Abstract

Objective:To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiological data from a large multicenter consortium of patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB).Methods:Supine and orthostatic blood pressure and structural magnetic resonance imaging data were extracted from PD and DLB patients evaluated at eight tertiary-referral centers in the USA, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm/Hg within 3 minutes of standing from the supine position (severe, ≥30/15 mm/Hg) and SH as a BP ≥140/90 mmHg with normal sitting blood pressure. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy, as well as WMH were appraised using validated semi-quantitative rating scales.Results:A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n= 170) had OH, including 24.7% (n= 42) with severe OH, and 41.7% (n= 71) with SH. OH was associated with global brain atrophy (p=0.004) and regional atrophy involving the anterior-temporal (p= 0.001) and medio-temporal (p=0.001) regions, greater in severe vs. non-severe OH (p=0.001). The WMH burden was similar in those with and without OH (p=0.49). SH was not associated with brain atrophy (p=0.59) or WMH (p=0.72).Conclusions:OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH were associated with WMH.

Differential impact of individual autonomic domains on clinical outcomes in Parkinson’s disease

“…In this context, we observed a higher incidence of dementia in patients with nOH and concomitant SH, suggesting a possible role of SH in promoting additional brain injury. However, this association should be interpreted with caution given our small sample size and contrasting results in the existing literature [26,29]. Furthermore, managing individuals that have nOH and concomitant SH often presents a clinical dilemma given the narrow therapeutic window for blood pressure targets -since treating nOH can worsen SH and vice versa [30].…”

“…Several theories exist to explain the pathophysiological mechanisms of this association. The "causative hypothesis" [25] posits that repeated episodes of cerebral hypoperfusion, often associated with increased BP variability and/ or hypertensive events, damage the brain cumulatively, which causes cortical damage [26]. The causative hypothesis is supported by animal models of neurodegenerative dementia, where it has been suggested that hypoperfusion could impair regional brain microcirculation, reducing the delivery of energy substrates needed for proper neuronal function.…”

Cognitive profile in idiopathic autonomic failure: relation with white matter hyperintensities and neurofilament levels

“…Association between cardiovascular AF, WMH load and cognitive impairment has never been described in patients with IAF. Many studies showed a relation between WMH load, cerebral hypoperfusion and different cognitive deficits in PD or DLB patients 39–41 and older populations, 42,43 others failed to show any significant association 44–49 . Recently, Palma et al.…”

“…Many studies showed a relation between WMH load, cerebral hypoperfusion and different cognitive deficits in PD or DLB patients [39][40][41] and older populations, 42,43 others failed to show any significant association. [44][45][46][47][48][49] Recently, Palma et al examined the single impact of SH on patients with PD, MSA or IAF reporting a close relation between SH and higher burden of target organ damage including cerebral WMH volume. 38 Although cognitive functions were not a primary endpoint of the study, the authors observed lower cognitive performances in patients with SH and higher burden of WMH, but without finding any significant correlations between WMH volume and cognitive scores.…”

“…Many studies showed a relation between WMH load, cerebral hypoperfusion and different cognitive deficits in PD or DLB patients 39 , 40 , 41 and older populations, 42 , 43 others failed to show any significant association. 44 , 45 , 46 , 47 , 48 , 49 Recently, Palma et al. examined the single impact of SH on patients with PD, MSA or IAF reporting a close relation between SH and higher burden of target organ damage including cerebral WMH volume.…”