Dataset Information

Effect of ALDH2 on Sleep Disturbances in Patients with Parkinson's Disease.

ABSTRACT: Monoamine neurotransmitters play essential roles in the regulation of arousal and sleep. Impaired metabolism of monoamine neurotransmitters could result in the accumulation of neurotoxic aldehyde metabolites and, hence, neuronal degeneration. Aldehyde dehydrogenases play an important role in the metabolism of the neurotoxic aldehyde metabolites, including the aldehyde metabolites of dopamine, serotonin, and noradrenaline. Deficient aldehyde dehydrogenase 2 (ALDH2) has been suggested to result in the accumulation of these biogenic aldehydes. An ALDH2 single nucleotide polymorphism (SNP), rs671 (A), results in significantly reduced ALDH2 enzyme activity. A total of 83 Parkinson's disease (PD) patients were recruited in this study. In addition to the genotypes of rs671, the patients were assessed with the PD sleep scale-2nd version (PDSS-2) and the Epworth sleepiness scale (ESS) for symptoms of daytime and nocturnal sleep disturbances. The patients carrying rs671 (A) had more frequent dozing while lying down to rest in the afternoon (ESS item5) (F?=?7.308, p?=?0.008) than the rs671 (GG) patients. The patients with rs671 (A) reported a trend toward more frequent difficulty staying asleep than the patients with rs671 (GG). (F?=?3.278, p?=?0.074). The results indicate that patients carrying allele rs671 (A) are more likely to experience impairment in the regulation of arousal and sleep. The results also support the hypothesis that the accumulation of neurotoxic monoamine neurotransmitter aldehyde metabolites secondary to reduced ALDH2 enzyme activity may cause more severe monoaminergic neuronal loss and, hence, more severe symptoms in the regulation of wakefulness and sleep.

SUBMITTER: Lin CY

PROVIDER: S-EPMC6908732 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Effect of ALDH2 on Sleep Disturbances in Patients with Parkinson's Disease.

Lin Chia-Yen CY Yu Rwei-Ling RL Wu Ruey-Meei RM Tan Chun-Hsiang CH

Scientific reports 20191212 1

Monoamine neurotransmitters play essential roles in the regulation of arousal and sleep. Impaired metabolism of monoamine neurotransmitters could result in the accumulation of neurotoxic aldehyde metabolites and, hence, neuronal degeneration. Aldehyde dehydrogenases play an important role in the metabolism of the neurotoxic aldehyde metabolites, including the aldehyde metabolites of dopamine, serotonin, and noradrenaline. Deficient aldehyde dehydrogenase 2 (ALDH2) has been suggested to result in ...[more]

PMID: 31831791

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Project description:Background:Nocturnal symptoms are common in Parkinson's disease (PD), which greatly affect the quality of life but are often overlooked in clinical settings. Treatment strategies that provide sustained dopaminergic stimulation may have sleep benefits. Objective:To investigate the treatment effects of pramipexole (PPX) sustained release (SR) versus PPX immediate release (IR) on nocturnal symptoms in advanced PD patients with sleep disturbances. Materials and methods:In this study, the PPX clinical trial (NCT00466167) was retrospectively analyzed for PD Sleep Scale (PDSS) total and domain scores in patients with advanced idiopathic PD receiving either PPX SR or PPX IR, who experienced motor fluctuations while on stable levodopa with a baseline PDSS total score of <90, indicating sleep disturbances. Analysis of covariance test was used to compare the adjusted mean changes at week 18 from baseline between treatment groups, after adjusting for pooled country and baseline scores. Results:A total of 119 patients with PD reported sleep disturbances at baseline (PDSS <90; SR, n=59; IR, n=60). At week 18, patients receiving PPX SR reported numerically greater improvement of sleep disturbance than those receiving PPX IR, although the difference of 6.8 points was not statistically significant (adjusted mean changes in PDSS total score, SR=28.5 versus IR=21.7 points, P=0.165). Patients receiving PPX SR observed a numerically greater adjusted mean change in all PDSS domains compared with PPX IR. The overall proportions of patients with any adverse event were similar between both PPX SR and IR groups (62.7% versus 70.0%). Conclusion:Both the PPX formulations showed improvements in nocturnal symptoms in advanced PD patients with sleep disturbances and were generally well tolerated. Given the known pharmacokinetic profile of an SR formulation and numerical advantage in PDSS mean change over IR formulation, these preliminary evidences support future prospectively designed studies to investigate the effects of PPX SR for improved sleep.

Project description:OBJECTIVES:Autoimmune encephalitis (AE) is increasingly recognized as an important cause of subacute cognitive decline, seizures, and encephalopathy, with an ever-broadening clinical phenotype. Sleep disturbances are reported in AE patients, including rapid eye movement sleep behavior disorder, hypersomnia, fragmented sleep, and sleep-disordered breathing; however, the prevalence of sleep disturbances and contributions to outcomes in AE patients remain unknown. There is a need to determine the prevalence of sleep disturbances in AE patients, and to clarify the relationship between specific autoantibodies and disruptions in sleep. METHODS:Clinical history, results of serum and cerebrospinal fluid testing, electroencephalography, and neuroimaging were reviewed from 26 AE patients diagnosed and managed at our tertiary care hospital. Polysomnography was performed in patients with clinical indications, yielding data from 12 patients. RESULTS:The median age of AE patients was 53 years (range 18-83). Autoantibodies against intracellular antigens (including Ma and Hu autoantibodies) were identified in 6/26 (23%) patients, while autoantibodies against cell-surface neuronal antigens (including NMDAR and LGI1) were identified in 20/26 (77%) patients. New sleep complaints were reported by 19/26 (73%) AE patients, including gasping or snoring (9/19, 47%), dream enactment behavior (6/19, 32%), insomnia (5/19, 29%), hypersomnia (4/19, 21%), other parasomnias (4/19, 21%), and dream-wake confusional states (2/19, 11%). Dream enactment behaviors were particularly common in AE associated with LGI1 autoantibodies, reported in 4/7 (57%) patients. Polysomnography showed reduced total sleep time, stage 3 and rapid eye movement sleep, and prominent sleep fragmentation. CONCLUSION:Sleep disturbances are common in AE, warranting active surveillance in affected patients. Improved identification and treatment of sleep disorders may reduce morbidity associated with AE and improve long-term outcomes.

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Effect of ALDH2 on Sleep Disturbances in Patients with Parkinson's Disease.

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Effect of ALDH2 on Sleep Disturbances in Patients with Parkinson's Disease.

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