Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients with REM behavior disorder whose nocturnal symptoms were markedly improved by treatment with the acetylcholinesterase inhibitor donepezil are reported. Donepezil may have a role in the treatment of REM behavior disorder, possibly through its actions on cholinergic pathways in the brainstem.
 ...
PMID:Treatment of REM sleep behavior disorder with donepezil: a report of three cases. 1099 12

Previous research in younger individuals has shown that acetylcholinesterase inhibitors may enhance REM sleep. The present study indicates that in the elderly, donepezil, an acetylcholinesterase inhibitor, also exerts a marked effect on REM sleep parameters--percentage of REM sleep and REM density were increased whereas REM latency was reduced. In addition, we also found a correlation between memory performance and REM sleep. Based on these findings, we conclude that there is an interrelationship between cognitive performance and amount of REM sleep in elderly humans as has been previously shown in animals and young adults.
 ...
PMID:Donepezil-induced REM sleep augmentation enhances memory performance in elderly, healthy persons. 1122 48

The cholinesterase inhibitor physostigmine (PHYS) was investigated in a double-blind, placebo-controlled, randomized, crossover trial of 10 male patients with moderate to severe obstructive sleep apnea. PHYS (0.12 microg/minute/kg, 7-hour infusion) reduced mean apnea/hypopnea index (AHI) by 13.6 (95% confidence interval [CI], 2.2-25.1) corresponding to 21.4% (95% CI, -5.5 to 47.9) and increased minimum SaO2 by 8.7% (95% CI, -0.3 to 17.7) corresponding to 23.2% (95% CI, 4.8-41.3). During the last third of the night, coinciding with predicted plasma concentration steady state, non-REM sleep AHI decreased by 19.2 (95% CI, 0.1-38.3) or 14.9% (95% CI, -43.6 to 77.7) and REM AHI by 33.8 (95% CI, 13.7-54.0) or 67.5% (95% CI, 49.7-85.3). Mean total sleep time was reduced by 74 minutes (95% CI, 33.9-114.9), but patients with the least pronounced sleep shortening had the largest reduction of AHI (r = 0.73, p < 0.02). The nocturnal decline in heart rate was reduced by PHYS. Moreover, resting (early-night placebo heart rate) was positively correlated with proportional reduction of REM apnea index (r = 0.69, p < 0.02). Body mass index was negatively correlated with reduction of REM AHI (r = 0.77, p < 0.02). This, predominantly REM-related, reduction of obstructive sleep apnea after PHYS may provide a new treatment option if the effects are maintained in long-term studies.
 ...
PMID:Reduction of sleep-disordered breathing after physostigmine. 1295 52

Dementia of the Alzheimer type (DAT) has been linked to losses of cholinergic function in the brain. The acetylcholinesterase inhibitors donepezil, rivastigmine and galantamine improve cognitive performance in manifest dementia. These substances, however, also influence the quality of sleep, and particularly the quality and amount of dreams. We therefore investigated the influence of the time point of donepezil intake on the occurrence of nightmares. We observed a clear-cut relationship between the occurrence of nightmares and an evening dose of donepezil in eight patients with DAT. None of these patients reported nightmares when donepezil was taken in the morning. We suggest that the activation of the visual association cortex during REM sleep is enhanced by donepezil, a mechanism most likely facilitating the development of nightmares in patients with DAT.
 ...
PMID:[Nightmares in patients with Alzheimer's disease caused by donepezil. Therapeutic effect depends on the time of intake]. 1563 Jun

The neuropsychiatry of Parkinson's disease (PD) and its correlates are reviewed. Dementia occurs in up to 30% and can be treated with cholinesterase inhibitors. Cognitive impairments involve executive, visuospatial, attentional, and memory dysfunctions. Apathy may respond to dopamine agonists or cholines-terase inhibitors. Cognitive impairment, psychosis, and depression predict quality of life. Visual hallucinations and paranoia are common, and respond to low dose clozapine. Depression is common and predicts caregiver burden and depression. The best data suggest the efficacy of nortriptyline and the safety of SSRIs. Anxiety disorders occur in 40% of patients, especially off-period panic attacks and specific phobias. Bromazepam has proven useful for anxiety in PD, but buspirone has only diminished drug-induced dyskinesias to date. Sleep disorders occur in up to 94% of patients. Insomnia is common and is treated by dopaminergic agent dose reduction, nocturnal dosing, treatment of depression, or use of short half-lived hypnotics, depending on etiology. Parasomnias include REM behavior disorder and vivid dreams and nightmares. Excessive daytime somnolence occurs in at least 15% of patients. Sleep attacks are common and patients should be warned about driving when taking dopamine agonists. Sexual disorders occur in most patients. Paraphilias are associated with dopamine agonists, and clozapine may be useful in their treatment. Surgical therapies are associated with a wide variety of neuropsychiatric features, and vigilance for suicide attempts with subthalamic nucleus stimulation seems warranted. Neuropsychiatric disorders are important determinants of quality of life and caregiver burden in PD. More clinical research is needed to establish effective treatments.
 ...
PMID:The neuropsychiatry of Parkinson's disease. 1617 59

Experimental approaches to manipulate REM sleep within the cognitive neuroscience of sleep are usually based on sleep deprivation paradigms and focus on younger adults. In the present study, a traditional selective REM sleep deprivation paradigm as well as two alternative manipulation paradigms targeting REM sleep augmentation were investigated in healthy older adults. The study sample consisted of 107 participants, male and female, between the ages of 60 and 82 years, who had been randomly assigned to five experimental groups. During the study night, a first group was deprived of REM sleep by selective REM sleep awakenings, while a second group was woken during stage 2 NREM sleep in matched frequency. Physiological REM sleep augmentation was realized by REM sleep rebound after selective REM sleep deprivation, pharmacological REM sleep augmentation by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Deprivation and augmentation paradigms manipulated REM sleep significantly, the former affecting more global measures such as REM sleep minutes and percentage, the latter more organizational aspects such as stage shifts to REM sleep, REM latency, REM density (only pharmacological augmentation) and phasic REM sleep duration. According to our findings, selective REM sleep deprivation seems to be an efficient method of REM sleep manipulation in healthy older adults. While physiological rebound-based and pharmacological cholinergic REM sleep augmentation methods both failed to affect global measures of REM sleep, their efficiency in manipulating organizational aspects of REM sleep extends the traditional scope of REM sleep manipulation methods within the cognitive neuroscience of sleep.
 ...
PMID:Manipulating REM sleep in older adults by selective REM sleep deprivation and physiological as well as pharmacological REM sleep augmentation methods. 1628 71

There is increasing evidence that acetylcholinesterase (AChE) may have various specific developmental roles in brain development. Nevertheless, specific effects of AChE inhibition during early brain development have not been adequately described. Therefore, methanesulfonyl fluoride (MSF), an irreversible AChE inhibitor that shows high selectivity for the CNS was used to produce AChE inhibition in utero to study subsequent adult behaviors, sleep, and cholinergic markers. Rats exposed to MSF in utero showed a deficit in spatial learning tasks using appetitive motivation but, surprisingly, they performed equally well or better than controls when aversive motivation was used. One hypothesis was that MSF treatment in utero affected the response to stress. Tests of anxiety however showed no differences in basal levels of anxiety. Studies of sleep behavior, however, indicated a higher level of REM sleep which is only seen during the light phase of male rats exposed to MSF in utero as compared to controls. No differences in cholinergic markers in the brains of adults were found except that females exposed to MSF in utero had a higher level of ChAT activity in the synaptosomal fraction of the hippocampus. Even so, whether cholinergic alterations accompany the in utero MSF exposure remains to be determined. The failure to find widespread changes in cholinergic markers in the adult brains suggests changes in behaviors should be further investigated by testing the participation of postsynaptic mechanisms, measuring of cholinergic markers during earlier development periods and the possible participation of other neurotransmitter systems to clearly reveal the role of the cholinergic system following in utero MSF exposure.
 ...
PMID:In utero methanesulfonyl fluoride differentially affects learning and maze performance in the absence of long-lasting cholinergic changes in the adult rat. 1792 Jan 11

Sleep deprivation disrupts various vital biological and metabolic processes that are necessary for health. The present study was designed to investigate the possible mechanisms of sleep deprivation-induced memory dysfunction by using different behavioral, biochemical and neurochemical parameters. Male Wistar rats were sleep deprived for 72 h using a grid suspended over water. Elevated plus maze, passive avoidance and Morris water maze tests were used to assess memory retention in 72-h sleep-deprived animals. Various electrophysiological (sleep-wake cycle), biochemical (lipid peroxidation, reduced glutathione, nitrite, catalase, acetylcholinesterase) and neurochemical parameters (norepinephrine, dopamine and serotonin) were also assessed. Sleep deprivation resulted in memory dysfunction in all the behavioral paradigms, alteration in the sleep-wake cycle (delayed sleep latency, shortening of rapid eye movement [REM] and non-REM [NREM] sleep and increased waking period) and oxidative stress (increased lipid peroxidation and nitrite levels, depletion of reduced glutathione and catalase activity). In addition, increased levels of acetylcholinesterase (AChE; the enzyme responsible for the degradation of acetylcholine) and reduction in norepinephrine and dopamine levels were seen in 72-h sleep-deprived animals. In conclusion, sleep deprivation-induced memory deficits may possibly be due to the combined effect of oxidative damage and alterations in neurotransmitter levels.
 ...
PMID:Possible mechanism involved in sleep deprivation-induced memory dysfunction. 1898 81

Alzheimer's disease (AD) is the most common cause of dementias. Mild cognitive impairment (MCI) indicates the situation that a person has memory complaints and mild objective cognitive impairment but no evidence of dementia. Sleep disturbance, one of the behavioral and psychological symptoms of dementia (BPSD), frequently occurs in patients with AD or MCI. The alteration of sleep architectures in AD patients remains inconclusive. In this study, we conducted the polysomnography. (PSG) examination among patients with mild AD with cholinesterase inhibitors (N=10) or MCI (N=12) and age-matched nondemented controls (N=13). The results showed sleep efficiency, which was one of the important parameters for sleep quality was significantly lower in patients with MCI and AD (N=22), 79.14 +/- 11.06 % vs. 67.07 +/- 19.10 %, p=0.046. There were no statistic differences of sleep architecture but a trend of REM insufficiency in patients with MCI or AD. The mean scores of geriatric depression score (GDS) and Epworth sleepiness scale (ESS) did not differ among the three groups. Our study implicated maintenance of sleep was impaired in patients with cognitive impairment and it was independent with depressive symptoms.
 ...
PMID:Low sleep efficiency in patients with cognitive impairment. 1967 60

We report the case of an 88-year-old man with Alzheimer's disease (AD) of 8 years duration (emerging shortly after the de novo onset of sleeptalking) who developed REM sleep behavior disorder (RBD) after increasing the nightly dose of rivastigmine, an acetylcholinesterase inhibitor, from 1.5 mg to 3 mg (total daily dose, 4.5 mg), as therapy for his dementia. His family then became aware of recurrent nocturnal episodes arising from sleep of his leaving bed, and he sustained multiple abrasion injuries from falling down. Polysomnography (PSG), utilizing a seizure montage with fast paper speed, conducted with the patient taking rivastigmine 3 mg at bedtime, documented 3 abrupt episodes of bilateral arm-waving with moaning and shouting that emerged exclusively during each of the 3 REM sleep periods, with the duration of the episodes lasting 8 to 25 seconds. No epileptiform discharge appeared with the onset of these REM sleep behaviors. Therapy with clonazepam, 0.5 mg at bedtime (with ongoing 3 mg bedtime and 4.5 mg total daily rivastigmine therapy), fully suppressed the sleep-related events, with prompt relapse whenever clonazepam was not taken. This is the second reported case (both males with AD) of rivastigmine-induced RBD, and the oldest reported case of RBD; and it represents reversible, medication-induced, acute RBD.
 ...
PMID:Rivastigmine-induced REM sleep behavior disorder (RBD) in a 88-year-old man with Alzheimer's disease. 2041 99


<< Previous 1 2 3 Next >>