Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with dementias, such as Alzheimer's disease (AD), often have nocturnally disrupted sleep. Clinically, this may present as agitation during the nighttime hours, which may affect as many as a quarter of AD patients during some stage of their illness. Sleep disturbance in AD may be multifactorial and involve sleep-disordered breathing and disrupted chronobiology, both often characterized by excessive daytime napping. Polysomnographically, AD patients show decreased rapid eye movement (REM) sleep in proportion to the extent of their dementia; some evidence suggests that cholinesterase inhibitors, commonly used pharmacologic agents for cognitive loss in AD, may increase REM sleep measures. Unfortunately, such agents may also induce insomnia and vivid dreams. There have been no randomized clinical trials of sedative-hypnotic medications specifically targeted at AD patients with sleep problems. Evidence suggests that sedative-hypnotics, such as benzodiazepine site-specific agonists, may have a role in some cases, whereas atypical antipsychotics may be necessary in other cases. There are also reports of successful interventions with nonpharmacologic options (eg, exercise, illumination). The utility of melatonin as a hypnotic in this population appears equivocal.
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PMID:Sleep disorders in Alzheimer's disease and other dementias. 1525 36

Doppel (Dpl) is a prion-like protein encoded by the gene PRND, which has been found downstream of the prion gene PRNP in several species. The present study examines by immunohistochemistry Dpl expression in brain samples from 10 patients with Alzheimer's disease (AD), three patients with Pick's disease, four patients with Parkinson's disease, eight patients with diffuse Lewy body disease (DLBD), six patients with sporadic Creutzfeldt-Jakob disease (CJD) methionine/methionine at the codon 129, two patients with sporadic CJD methionine/valine at the codon 129 and numerous kuru plaques in the cerebellum, one patient with fatal familial insomnia (FFI), and 10 age-matched controls. In the adult human brain, Dpl immunoreactivity was restricted to scattered granule cells of the cerebellum and scattered small granules in the cerebral cortex. Dpl immunoreactivity was seen around betaA4 amyloid deposits in neuritic plaques, but not in diffuse plaques, AD and the common form of DLBD. Neurofibrillary tangles, Pick bodies and Lewy bodies were not stained with anti-Dpl antibodies. No modifications in Dpl immunoreactivity were observed in CJD excepting those associated with accompanying senile plaques. No Dpl-positive deposits were seen in FFI. Whether Dpl in neuritic plaques may attenuate amyloid-induced oxidative stress and participate in the glial response around amyloid cores is discussed in light of the few available data on Dpl functions.
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PMID:Selective PrP-like protein, doppel immunoreactivity in dystrophic neurites of senile plaques in Alzheimer's disease. 1530 78

Daytime sedation is a common and potentially dose-limiting side effect of the opiate analgesics. The psychostimulants, such as methylphenidate, are frequently prescribed to treat this problem, but their use may be limited by side effects, such as weight loss, anxiety, or insomnia, or tolerance to their antisedative effects. Medications which enhance intracerebral cholinergic activity may offer an alternative treatment approach, since functional deficits of acetylcholine may, in part, account for the sedative and mind-dulling effects of opiates. Preliminary studies with donepezil, a centrally acting acetylcholinesterase (AChE) inhibitor approved for use in Alzheimer's disease, have suggested at least short-term benefit in treating opiate-related sedation. In a retrospective study, we reviewed the results of donepezil treatment in 40 patients, 37 of whom had cancer, which in most cases was in an advanced stage. All patients were receiving chronic opiate treatment, and the majority were on a stable opiate dose in the 2 weeks preceding the initiation of donepezil. The average opiate dose was 844 mg in oral morphine equivalents. Seventy-three percent of the patients experienced moderate or greater improvement on the Clinical Global Improvement Scale. Evaluations on the Epworth Sleepiness Scale (ESS; 0-24), visual analog sleepiness scale (VAS; 0-100), and average pain levels (0-100), before and after donepezil treatment, were obtained on 19 patients. Prior to donepezil, ESS, VAS, and pain scores were 18.5, 76.3, and 47.4. After an average of 21 days of donepezil treatment, scores were 9.5 (P < 0.001), 39.5 (P < 0.001), and 36.6 (P = 0.07), respectively. The mean total duration of treatment for patients was 54.4 days, with most patients stopping donepezil due to progression to a terminal state. Patients were generally started on 5 mg/ day, but 17 patients required higher doses to achieve or maintain efficacy, the average treatment dose being 9.13 mg/day. We concluded from this study that centrally acting AChE inhibitors are promising agents in the treatment of sedation,and perhaps of other neuropsychological side effects associated with the use of opiate analgesics.
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PMID:Treatment of opiate-related sedation: utility of the cholinesterase inhibitors. 1535 44

Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug-drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients. Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors. There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use. Data from single- and multiple-dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both in vitro and clinical studies have shown that donepezil is not associated with drug-drug interactions. The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia and other sleep disorders have been reported following administration of donepezil, lengthening the time period before increasing the dose of donepezil from 5 to 10 mg day(-1) or switching to morning dosing can reduce these events to the levels of placebo-treated patients. Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.
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PMID:The safety and tolerability of donepezil in patients with Alzheimer's disease. 1549 17

In clinical trials, short-term galantamine treatment produces consistent positive effects on global ratings, cognitive tests, and assessments of activities of daily living and behavior in patients with mild-to-moderate Alzheimer's disease (AD), providing the rationale for longer-term, open-label treatment. In this continuation trial following enrollment in previous 12-month trials, patients received galantamine 24 mg/day for a total of 24 months (total exposure up to 36 months). Primary efficacy measures were the ADAS-cog/11 and DAD. Adverse events (AEs) were coded to WHO preferred terms, including AEs begun in previous trials. Initial improvement in cognitive function was followed by a gradual decline, as measured by increased ADAS-cog/11 scores. At 36 months, ADAS-cog/11 scores increased by a mean (SEM) of 12.4 (0.80) points (P < 0.001) versus a projected 22-point increase for untreated patients. Functional abilities, as measured by the DAD, had decreased significantly at each time point versus baseline (P < 0.001). The most common treatment-emergent AEs were agitation (16.1%), insomnia (12.4%), fall (11.2%), and urinary tract infection (10.2%). AEs were mainly mild to moderate, appropriate for an elderly population, with few judged treatment related. Galantamine 24 mg/day is safe and effective for long-term treatment of mild-to-moderate AD. Potential exists for prolonged benefit with galantamine therapy versus lack of treatment for the long-term.
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PMID:Long-term efficacy and safety of galantamine in patients with mild-to-moderate Alzheimer's disease: multicenter trial. 1552 94

In case a pre-senile patient presented subacutely progressive dementia, secondary dementia, such as paraneoplastic neurological syndrome (PNS), hypothyroidism, confusion, early phase of primary degenerative dementia and prion diseases are to be considered. It is a case of pathologically confirmed, and clinico-pathologically assessed limbic encephalitis with cerebellar degeneration. The patient was a 63-year old male, with a well followed up medical history of gastric cancer 8 years earlier. Four weeks after he presented himself at our hospital his memory and disorientation progressively declined. A neurological examination revealed gaze nystagmus, with potential secondary dementia. However, no abnormal findings were detected from systemic radiological examination, or from chemical analyses. Two months later, after the onset of the disease, he presented additional symptoms, including seizure, gait disturbance, and insomnia. On admission, neurological examinations revealed gaze nystagmus and progression of dementia; however, his thought process was relatively preserved. No paroxysmal synchronized discharge was seen on electroencephalogram. Chest X-rays showed an inflammatory infiltration. In spite of anti-biotic medication, he died due to respiratory failure. The autopsy was limited to the brain. Histologically, limited lymphocytic infiltration into the hippocampus through the entorhinal cortex, with marked neuronal loss and gliosis was observed. Neuronophagia, microglial nodules, and perivascular lymphocytic infiltration were also seen. Additionally, most of the Purkinje cells in the cerebellum were lost, with Bergmann's gliosis and sparse lymphocytic infiltration. No tumor was observed in the brain. Pathological findings of the brain were compatible with paraneoplastic limbic encephalitis and cerebellar degeneration, though no neoplasm, clinically or pathologically, was detected in this patient. Consequently, it is suggested that when a senile patient presents sub-acute onset of progressive dementia, with a variety of neurological symptoms, paraneoplastic syndrome is to be taken into consideration, even if a tumor or an auto-antibody is not detected since the resection of the tumor is still the best therapeutic means. Otherwise immuno-suppressive and steroid therapies should be used.
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PMID:A pre-senile case of limbic encephalitis and cerebellar degeneration, with subacute onset of progressive dementia. 1567 63

There is a hypothesis that dangerous diseases such as bovine spongiform encephalopathy, Creutzfeldt-Jakob, Alzheimer's, fatal familial insomnia, and several others are induced by propagation of wrong or misfolded conformations of some vital proteins. If for some reason the misfolded conformations were acquired by many such protein molecules it might lead to a "conformational" disease of the organism. Here, a theoretical model of the molecular mechanism of such a conformational disease is proposed, in which a metastable (or misfolded) form of a protein induces a similar misfolding of another protein molecule (conformational autocatalysis). First, a number of amino acid sequences composed of 32 aa have been designed that fold rapidly into a well defined native-like alpha-helical conformation. From a large number of such sequences a subset of 14 had a specific feature of their energy landscape, a well defined local energy minimum (higher than the global minimum for the alpha-helical fold) corresponding to beta-type structure. Only one of these 14 sequences exhibited a strong autocatalytic tendency to form a beta-sheet dimer capable of further propagation of protofibril-like structure. Simulations were done by using a reduced, although of high resolution, protein model and the replica exchange Monte Carlo sampling procedure.
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PMID:Theoretical model of prion propagation: a misfolded protein induces misfolding. 1591 70

This work describes the reasons and emotional responses of healthy descendants after counseling for presenilin mutations in early-onset familial Alzheimer's disease (EOFAD), tau mutations in familial frontotemporal dementia (FTD), and prion mutations in fatal familial insomnia (FFI). A multidisciplinary protocol following Huntington's disease counseling guidelines and a post-test follow-up program were developed to counsel healthy descendants of affected families. The psychological consequences, anxiety levels, and depression status were assessed through validated scales before and after disclosing the information. Nine people from three different families, one with EOFAD, another with FTD, and the other with FFI came for counseling. Their main reason for testing was to initiate early treatment in the future. Disclosing the information decreased anxiety in two carriers, increased it temporarily in one, and had no effect in another. All noncarriers felt relieved. Overall, after a mean of 30 months of follow-up, no negative psychological reactions were observed. All participants positively valued the program. Although preliminary, our observations suggest that predictive testing in EOFAD, FTD, and FFI is safe and may be of benefit when performed with a delicate approach under strict pretest counseling protocols and post-test follow-up programs. The emotional reactions were similar, although the diseases, their phenotype, and mutation characteristics were different.
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PMID:Emotional reactions to predictive testing in Alzheimer's disease and other inherited dementias. 1613 47

Western medicine was introduced to Taiwan in 1865 when Dr. James L. Maxwell, a missionary doctor of the English Presbyterian Church, established a hospital in nowadays Tainan. The period of the missionary medicine lasted for over 30 years until Japanese took over. During this period, however, official records of diseases in Taiwan that were based on Western medicine were scanty or not available. Fortunately, port surgeons stationing respectively in Tamsui and Kelung in the north and in Takow and Taiwan-fu in the south reported semi-annually diseases seen in the ports, foreign communities and missionary hospitals that they volunteered to work. The diseases reported by port surgeons were either cases or summary of cases with classification and statistics. Their medical reports covered from 1871 to 1900. The data show that neurological diseases and/or disorders in the late 19th century Taiwan were uncommon, comprising only 2-3% of total diseases. The data further show that common neurological diseases were leprosy, opium smoking, syphilitic dementia (GPI), paralysis, hysteria, neuralgia, epilepsy, mania, sciatica, meningitis and ataxia. Stroke was uncommon while Parkinson's disease and Alzheimer's disease were not mentioned, indicating that neurological diseases related to old age and neurodegeneration were not yet a threat to health. Similarly, headache, insomnia, anxiety and depression, hallmark of functional disorders of the modern society, were also not mentioned, suggesting that these disorders were indeed rare or did not cause sufficient concern for patients to seek help from doctors of Western medicine.
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PMID:[Neurological diseases in late 19th century Taiwan--medical reports of the Chinese Imperial Maritime Customs]. 1642 51

Prion diseases for the most part affect individuals older than 60 years of age and share features with other diseases characterized by protein deposits in the brain, such as Alzheimer's disease and Parkinson's disease. The international conference "Prion 2005: Between Fundamentals and Society's Needs," organized by the German Transmissible Spongiform Encephalopathies Research Platform, aimed to integrate and coordinate the research efforts of participants to better achieve prevention, treatment, control, and management of prion diseases, including Creutzfeldt-Jakob disease and fatal familial insomnia in humans. Several main topics were discussed, such as the molecular characteristics of prion strains, the cell biology of cellular and pathogenic forms of the prion proteins, the pathogenesis of the diseases they cause, emerging problems, and promising approaches for therapy and new diagnostic tools. The presentations at the Prion 2005 conference provided new insights in both basic and applied research, which will have broad implications for society's needs.
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PMID:Prion 2005: Between Fundamentals and Society's Needs. 1643 84


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