Relationship between cardiovascular autonomic failure and cognitive performance in the ?-synucleinopathies: preliminary cross-sectional analysis of the Natural History Study of Synucleinopathies (NHSS) registry

Cardiovascular autonomic failure, presenting with neurogenic orthostatic hypotension (nOH) and supine hypertension (SH), is a common non-motor feature of the α-synucleinopathies. High blood pressure (BP) variability may foster end-organ damage and promote cognitive impairment. Nevertheless, the interplay between cardiovascular dysautonomia and cognitive performance in α-synucleinopathies is yet unclear. We therefore analyzed data from 76 Parkinson´s Disease (PD), 282 Multiple System Atrophy (MSA) and 133 stable pure autonomic failure (PAF) patients enrolled in the Natural History Study of Synucleinopathies (NHSS). The Montreal Cognitive Assessment (MoCA) was used to test patients’ baseline cognitive performance. Orthostatic hypotension (OH), neurogenic OH (nOH) and SH were defined based on supine-to-standing heart rate and BP measurements contemporary to cognitive testing. In PD, 36% of patients (n=26) had no OH, 15% (n=11) non-neurogenic OH, 11% (n=8) nOH and 38% (n=28) both nOH and SH. In PAF 8% of patients (n=9) showed no OH, 21% (n=24) non-neurogenic OH, 12% (n=14) nOH and 58% (n=66) both nOH and SH. In MSA, 25% of patients (n=65) had no OH, 17% (n=45) non-neurogenic OH, 16% (n=43) nOH and 42% (n=114) both nOH and SH. In our cross-sectional analysis, median MoCA scores did not differ across PD (p=0.108) and PAF (p=0.453) patients with and without baseline orthostatic BP dysregulation. In MSA, the nOH subgroup showed higher median MoCA scores (p=0.036) compared to the other groups but different clinical-demographic features may account for this observation. The longitudinal analysis of MoCA score changes according to baseline BP dysregulation will clarify the impact of cardiovascular dysautonomia on the progression of cognitive impairment in the α-synucleinopathies