Objective: To compare cognitive performances of patients with α-synucleinopathies with or without cardiovascular dysautonomia.

Background: Cardiovascular dysautonomia is a disabling non-motor feature of the α-synucleinopathies and may foster end-organ damage. The interplay between cognitive impairment and dysautonomia is however not clear yet.

Method: We analyzed data from the Natural History Study of Synucleinopathies. The Montreal Cognitive Assessment (MoCA) was used to test cognitive function. Orthostatic hypotension (OH)¹, neurogenic OH (nOH)² and supine hypertension (SH)³ were diagnosed with supine-to-standing heart rate and blood pressure (BP) measurements at the time of cognitive testing.

Results: We included 76 Parkinson’s disease (PD), 133 stable pure autonomic failure (PAF) and 282 multiple system atrophy (MSA) patients. Baseline median MoCA score was lowest in PD (p=0.003). 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) had no OH, 21% (n=24) non-neurogenic OH, 12% (n=14) nOH and 58% (n=66) both nOH and SH. Both in PD and PAF MoCA scores did not differ across these groups (p=0.108 and 0.453, respectively). In MSA, 25% of patients (n=65) had no OH, 17% (n=45) non-neurogenic OH, 43% (n=16) nOH and 42% (n=114) both nOH and SH. The MoCA scores were higher in MSA patients with nOH (p=0.036) and in those with autonomic [28 (25; 30)] versus motor onset [26 (23; 29), p=0.015].

Conclusion: We found no differences in median MoCA scores across PD and PAF patients with or w/o any form of BP dysregulation, suggesting that the neuropathological substrate of dysautonomia and cognitive impairment may differ in neuronal α-synucleinopathies. In MSA, nOH patients showed slightly higher MoCA scores. Different clinical-demographic features across orthostatic BP patterns, e.g. autonomic vs. motor onset, might explain this result. Analysis of the longitudinal MoCA score changes according to the baseline BP phenotype will help clarifying the impact of cardiovascular dysautonomia on the progression of cognitive impairment in α-synucleinopathies.
*Preliminary results of this study were presented at: 2021 ÖPG Jahrestagung (Graz-October, 22), 2021 EFAS meeting (Virtual-November, 27), 2022 Otto Loewi Gesellschaft Jahrestagung (Innsbruck-February, 25)

References: 1 Brignole M, Moya A, de Lange FJ, et al., 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018 Jun 1;39(21):1883-1948. doi: 10.1093/eurheartj/ehy037.
2 Norcliffe-Kaufmann L, Kaufmann H, Palma JA, et al. Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Ann Neurol. 2018 Mar;83(3):522-531. doi: 10.1002/ana.25170.
3 Fanciulli A, Jordan J, Biaggioni I, et al., Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS): Endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH). Clin Auton Res. 2018 Aug;28(4):355-362. doi: 10.1007/s10286-018-0529-8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/relationship-between-cardiovascular-autonomic-failure-and-cognitive-performance-in-the-%ce%b1-synucleinopathies-preliminary-cross-sectional-analysis-of-the-nhss-registry/