Aim: To understand why autonomic failures, a common non-motor symptom of Parkinson's disease (PD), occur earlier than typical motor disorders.
Methods: Vagal application of DOPAL (3,4-dihydroxyphenylacetaldehyde) to simulate PD-like autonomic dysfunction and understand the connection between PD and cardiovascular dysfunction. Molecular and morphological approaches were employed to test the time-dependent alternation of α-synuclein aggregation and the ultrastructure changes in the heart and nodose (NG)/nucleus tractus solitarius (NTS).
Results: Blood pressure (BP) and baroreflex sensitivity of DOPAL-treated rats were significantly reduced accompanied with a time-dependent change in orthostatic BP, consistent with altered echocardiography and cardiomyocyte mitochondrial ultrastructure. Notably, time-dependent and collaborated changes in Mon-/Tri-α-synuclein were paralleled with morphological alternation in the NG and NTS.
Conclusion: These all demonstrate that early autonomic dysfunction mediated by vagal application of DOPAL highly suggests the plausible etiology of PD initiated from peripheral, rather than central site. It will provide a scientific basis for the prevention and early diagnosis of PD.
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http://dx.doi.org/10.1111/cns.13589 | DOI Listing |
J Neurol
January 2025
Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.
Background And Objective: Non-motor symptoms frequently develop throughout the disease course of Parkinson's disease (PD), and pose affected individuals at risk of complications, more rapid disease progression and poorer quality of life. Addressing such symptom burden, the 2023 revised "Parkinson's disease" guideline of the German Society of Neurology aimed at providing evidence-based recommendations for managing PD non-motor symptoms, including autonomic failure, pain and sleep disturbances.
Methods: Key PICO (Patient, Intervention, Comparison, Outcome) questions were formulated by the steering committee and refined by the assigned authors.
Alzheimers Dement
December 2024
Queen Mary University of London, London, United Kingdom.
Background: Alzheimer's disease (AD) is associated with a range of non-cognitive symptoms that can be early or even presenting features. Better recognition of pre-diagnostic symptoms of AD would support improved early detection and diagnosis.
Method: To identify possible prodromal symptoms of AD, we systematically searched three electronic databases for prospective longitudinal studies to March 2023, that reported the risk of AD diagnosis associated with non-cognitive symptoms.
Alzheimers Dement
December 2024
ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Research Consortium, CA, USA.
Background: Autonomic dysfunction has been linked to empathy deficits in symptomatic frontotemporal degeneration (FTD), but less is known about pre-symptomatic FTD mutation carriers (preFTD+). Our prior work found that increasing resting heart rate (RHR) over time predicts decline in emotional empathy in preFTD+. Here, we replicate previous findings in a large, multi-site consortium sample and assess relationships between RHR and empathy loss across disease stages.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Banner Sun Health Research Institute, Sun City, AZ, USA.
Background: Lewy body (LB) diseases can present with overlapping prodromal, cognitive, motor, autonomic or neuropsychiatric symptoms. Intuitively, greater symptom severity should correlate with greater pathological burden, but this has not been consistently shown. LB pathology does not translate to clinical expression in Incidental LB disease.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Case Western Reserve University, Cleveland, OH, USA.
Background: A patient presented to movement disorder clinic with cognitive complaints, imbalance and prior diagnosis of NPH. The patient underwent ventriculoperitoneal shunt in the past with minimal improvement, a detailed history is suggestive of REM sleep behavioral disorder, autonomic dysfunction including orthostatic hypotension and urinary incontinence.
Method: Clinical evaluation was notable for bradykinesia, rigidity, truncal and cervical dystonia, shuffling steps, reduced arm swing bilaterally and pink, dusky skin of both hands.
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