Cognitive and Autonomic Dysfunction in Multiple System Atrophy Type P and C: A Comparative Study

Abstract

Multiple System Atrophy (MSA) is a rare neurodegenerative disease, clinically defined by a combination of autonomic dysfunction and motor involvement, that may be predominantly extrapyramidal (MSA-P) or cerebellar (MSA-C). Although dementia is generally considered a red flag against the clinical diagnosis of MSA, in the last decade the evidence of cognitive impairment in MSA patients has been growing. Cognitive dysfunction appears to involve mainly, but not exclusively, executive functions, and may have different characteristics and progression in the two subtypes of the disease (i.e., MSA-P and MSA-C). Despite continued efforts, combining in-vivo imaging studies as well as pathological studies, the physiopathological bases of cognitive involvement in MSA are still unclear. In this view, the possible link between cardiovascular autonomic impairment and decreased cognitive performance, extensively investigated in PD, needs to be clarified as well. In the present study, we evaluated a cohort of 20 MSA patients (9 MSA-P, 11 MSA-C) by means of a neuropsychological battery, hemodynamic assessment (heart rate and arterial blood pressure) during rest and active standing and bedside autonomic function tests assessed by heart rate variability (HRV) parameters and sympathetic skin response (SSR) in the same experimental session. Overall, global cognitive functioning, as indicated by the MoCA score, was preserved in most patients. However, short- and long-term memory and attentional and frontal-executive functions were moderately impaired. When comparing MSA-P and MSA-C, the latter obtained lower scores in tests of executive functions and verbal memory. Conversely, no statistically significant difference in cardiovascular autonomic parameters was identified between MSA-P and MSA-C patients. In conclusion, moderate cognitive deficits, involving executive functions and memory, are present in MSA, particularly in MSA-C patients. In addition, our findings do not support the role of dysautonomia as a major driver of cognitive differences between MSA-P and MSA-C.

Characteristics of Mild Cognitive Impairment and Associated Factors in MSA Patients

“…The impaired spontaneous immediate verbal recall is a main feature of MSA-P [ 5 , 14 ], which was similar to the pattern of Parkinson’s disease. However, reports exist on a more prominent impairment of memory, executive functions, and attention deficit in MSA-C [ 9 , 30 , 31 ]. Fabian Maass et al [ 32 ] showed that MSA-C patients presented poor performance in language items compared with MSA-P patients.…”

Cardiac autonomic control in Rett syndrome: Insights from heart rate variability analysis

“…HRV is closely regulated by the central autonomic network involving brainstem, prefrontal cortex, limbic system, and other higher-order brain structures. To note, a shift of the autonomic balance toward a sympathetic predominance has been associated with a higher risk of mortality ( Tsuji et al, 1996 ; Malliani and Montano, 2002 ), and highlighted as a prognostic marker of adverse clinical outcome in cardiopulmonary ( Tobaldini et al, 2020 , 2021 ), neurodegenerative ( Carandina et al, 2022 ; Lazzeri et al, 2022 ) and autoimmune ( Rodrigues et al, 2019 , 2022 ) diseases. In recent years, the study of HRV has found increasingly wide applications, opening up fascinating research fields in various neurological and neuropsychiatric disturbances.…”