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Region Hovedstaden - en del af Københavns Universitetshospital

Autonomic Function in Neurodegenerative Diseases

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandling


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Neurodegenerative diseases are highly debilitating and often lead to severe morbidity and even death. Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. According to the Braak staging study, the progressionof PD starts in the medulla oblongata, which includes the cardiac centre and controls autonomic functions, and therefore autonomic dysfunction may be experienced early in the disease course.
Sleep disturbances are also common non-motor complications of PD, and therefore PD patients undergo polysomnography at the Danish Center for Sleep Medicine to assess the sleep disturbances. The aim of this PhD dissertation was to: 1) Develop a method to investigate autonomic changes during sleep in neurodegenerative diseases, and apply this method on PD, iRBD and narcolepsy patients to evaluate the autonomic function in these diseases. 2) Validate the method by applying standardized methods to measure the autonomic function based on heart rate variability (HRV) measures.
3) Based on the results, assess the validity of autonomic dysfunction as an early marker of a neurodegenerative disease. 4) Evaluate the influence of hypocretin loss in narcolepsy patients on autonomic function and on the sleep transition rate.
The results showed an attenuated heart rate response (HRR) in PD patients compared to controls and early PD (iRBD patients). Also iRBD patients had an attenuated HRR compared to control subjects, and the method to measure the HRR may be a possible screening tool to identify a neurodegenerative disease early in the disease course. Based on the HRV measures, when validating the method, it was found that sympathetic activity was attenuated in iRBD patients which was further pronounced in PD patients.
Parasympathetic activity, emanating from the nucleus ambiguus, may be relatively preserved in patients with PD. The progressive reduction of sympathetic nervous activity is in line with the postganglionic sympathetic nervous dysfunction seen in early PD and may represent an early manifestation of a neurodegenerative process involving brain stem areas, which is consistent with the Braak hypothesis.
In the narcolepsy patients, it was shown that a reduced HRR to arousals was primarily predicted by hypocretin deficiency in both rapid-eye-movement (REM) and non-REM sleep, independent of cataplexy and other factors. The results confirm that hypocretin deficiency affects the autonomic nervous system of patients with narcolepsy and that the hypocretin system is important for proper heart rate modulation at rest.Furthermore, it was shown that hypocretin deficiency and cataplexy are associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches. The increased frequency of transitions may cause increased sympathetic activity during sleep and thereby increased heart rate, or the increased heart rate could be caused by decreased
parasympathetic activity due to the lack of hypocretin signalling.
StatusUdgivet - 2013

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