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)

Many therapeutic effects of benzodiazepines are mediated by neuronal high-affinity binding sites, i.e. benzodiazepine receptors (BR), located on GABAA receptors. Recently, endogenous BR ligands have partially been identified which, as agonists, either increase or, as inverse agonists, decrease GABAergic inhibition in the brain. BR antagonists, previously described as intrinsically inactive, induce effects in animals and humans under particular circumstances emphasizing a functional relevance of endogenous BR ligands. Several brain disorders, e.g. anxiety, insomnia, epilepsy, spasticity, alcoholism, coma, dementia, may be associated with a disequilibrium of opposing endogenous BR ligands changing the excitability of neurons implicated in aforementioned diseases. It is proposed that, depending on the relative role endogenous BR ligands play in the pathophysiology of these disorders, BR antagonists might demonstrate a variable efficacy in improving their symptomatology. In fact, such therapy would restore the homeostatic balance among various endogenous BR ligands being disturbed during an illness.
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PMID:Involvement of endogenous benzodiazepine receptor ligands in brain disorders: therapeutic potential for benzodiazepine antagonists? 747 87

Alzheimer's disease (AD) primarily results in memory impairment and cognitive deficits in areas such as language, visuospatial function, calculation, praxis and judgement. However, over 30% of patients with dementia develop a group of secondary behavioural disturbances, including depression, hallucinations and delusions, agitation, insomnia and wandering. Because these secondary symptoms impair patients' function, increase their need for supervision, and often influence the decision to institutionalise them, the control of these symptoms is a priority in managing AD. Psychotropic drugs, particularly antipsychotics (neuroleptics), have been a mainstay in treating many of these symptoms, but carry a high risk of adverse effects. Patients with AD may be particularly vulnerable to adverse effects of medications because of changes in pharmacokinetics and neurotransmitter systems, related to both AD and aging. At present, treating secondary symptoms of AD is more of an art than a science. For virtually every group of symptoms, older and newer classes of medications are available, with proven efficacy in patients without dementia and less clear results in AD patients. We review current treatment options and suggest preferences for each symptom complex, based on a trade-off between efficacy and adverse effects. New agents, such as selective serotonin reuptake inhibitors and atypical antipsychotics, may herald the arrival of symptom- (and receptor-) specific drugs with minimal adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adjunctive therapy in patients with Alzheimer's disease. A practical approach. 757 86

Several factors have been reported to predict death and institutionalization in demented patients, even if the results of the studies are often conflicting. We conducted a study on a group of 86 consecutive noninstitutionalized probable Alzheimer disease (AD) patients, to evaluate clinical and social factors predicting mortality and institutionalization 1 year after discharge from the Alzheimer Dementia Unit at 'Sacro Cuore Fatebenefratelli' Hospital, Brescia, Italy. The 1-year mortality rate was 13.9% and the 1-year rate of admission to a nursing home was 34%. Our data indicate that the number of lost functions on the Activity of Daily Living scale is the most important predictor of short-term mortality, independently of the degree of cognitive impairment, the duration of the dementia, the age of the patients and the number of chronic diseases. Our data also demonstrate that, in a short period of observation, behavioral disturbances (and in particular insomnia) and availability of social services play a major role in the decision to institutionalize AD patients.
Dementia
PMID:Predictors of mortality and institutionalization in Alzheimer disease patients 1 year after discharge from an Alzheimer dementia unit. 760 78

Originally described by Lugaresi et al. in 1986 (ref. 1), fatal familial insomnia (FFI) is a rare inherited neurological disease characterized by the subacute progression of intractable insomnia and other autonomic abnormalities, cerebellar and pyramidal signs, myoclonus and dementia; neuropathologically, the major feature is severe neuronal loss with associated gliosis in the ventral and mediodorsal thalamic nuclei. The disease has been related to the group of spongiform encephalopathies by virtue of the presence of low levels of proteinase-resistant amyloid protein (PrPres) in the brain, and of a pathogenic single-allele mutation at codon 178 of the PRNP gene that encodes PrPres (refs 2, 5). Here we report the successful transmission of the disease to experimental animals, placing FFI within the group of infectious cerebral amyloidoses.
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PMID:First experimental transmission of fatal familial insomnia. 763 Apr 20

We report a 42-year-old man who, for 8 months, had intermittent motor abnormalities and mild difficulty falling asleep. A diagnosis of fatal familial insomnia (FFI) became evident over the next 6 months when he developed progressive insomnia, myoclonus, sympathetic hyperactivity, and dementia. The amyloid or prion protein (PrP) genotype showed features typically seen in FFI, with a 178Asn mutation and a 129Met polymorphism. There was also a deletion of one octapeptide repeat, suggesting that the association of 178Asn mutation with the 129Met polymorphism is not due to "founder effect." Western immunoblot showed a trace of protease-resistant PrP in the thalamus--which had the most significant neuronal loss and gliosis--a moderate amount of PrP in the fronto-temporal area, and no detectable protein elsewhere in the brain. Endocrine studies showed that a circadian modulation of hormonal levels could be maintained despite a near-total absence of sleep. Administration of gamma-hydroxybutyrate induced a remarkable increase in slow-wave sleep.
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PMID:Clinical and genetic studies of fatal familial insomnia. 778 65

The discovery of the presynaptic histamine H3 receptors confirmed the idea that histamine is a neurotransmitter in the mammalian brain. The H3 receptors (autoreceptors) regulate the release and synthesis of histamine. The H3 receptors also modulate the other neurotransmitters (heteroreceptors). Subclasses of H3 antagonist binding sites were found in the brain (H3A and H3B). The regulation of noradrenaline release is reported to be mediated by H3A rather than H3B. The H3 binding site belongs to the class of receptors coupled to G-proteins. Besides the molecular data, this review focuses on the functional roles of H3 receptors in the brain and discusses the possible use of H3 ligands for neurobehavioral disorders. The pharmacological data of H3 ligands may provide clinical candidates for CNS disorders in which histamine plays important roles in mental and behavioral functions. Especially, H3 antagonists may be useful for CNS disorders such as narcolepsy, dementia, epilepsy, and obesity, while H3 agonists may provide for anxiety, insomnia, migraine. However, these suggestions are still preliminary and further clinical research is needed, although potent and safe novel H3 ligands are being developed.
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PMID:[Possible roles of brain histamine H3 receptors and the pharmacology of its ligands]. 779 25

The follow-up of an important number of patients during the last three decades has shown a substantial difference between the clinical description of pellagra in the 40's (the triad: dermatitis, diarrhea, dementia) and its clinical aspects today: sun-exposed teguments revealing erythema and rapidly becoming pigmented and parchment like, dried, parched lips, angular stomatitis, lead like sclera fine cornea vascularization; gastro-intestinal disturbances: constipation, unjustified diarrhea, strange migratory abdominal feelings accompanied by ubiquitous dysesthesias. Other characteristics of this form of disease are: unexpressive look, continuously concerned, thoughtful, anxious or frowning, labile mind, headaches, insomnia. Villager's neurosis sometimes may be considered, in an appropriate clinical context, as a facet of nutritional deficiency. It is considered that the "classical" features of pellagra have changed due to: protein ingestion slightly below the lowest normal limit, decrease of strenuous physical activity and some associated diseases (frequently gastrointestinal disorders, chronic alcoholism).
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PMID:Particular features of clinical pellagra. 792 Mar 32

Comprehensive treatment of patients with parkinson's disease demands that not only motoric dysfunctions but also psychosocial aspects have to be considered. The scope of this review is to cover not only the frequent dementia and depressive states associated with this disease, but also the drug-induced behavioral abnormalities, insomnia, conflicts with those providing care and implications for professional activities. The fundamental pathophysiological and psychopathological mechanisms are explained and illustrated by examples.
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PMID:[Mental suffering IN patients with parkinsonism]. 793 73

As part of a case-control study, the psychiatric symptoms and behavioral problems of 61 multi-infarct dementia (MID) cases and 86 multi-infarct controls without dementia were compared to determine the prevalence of psychiatric symptoms and to clarify psychiatric predictors of dementia associated with cerebral infarcts. Ninety-two percent of the cases and 85% of the controls were African American. Cases were generally older, less well educated, and had a greater number of strokes and more neurologic deficits than controls. The most frequent psychiatric symptoms as reported by caregivers of patients with MID were irritability (57.3%), apathy (44.4%), insomnia (43.6%), agitation (40.7%), impatience (37%), and emotional lability (28.3%). In multivariate analysis, apathy and irritability were independent predictors of dementia associated with cerebral infarcts unless tests of cognitive function were added to the model. Our findings suggest that psychiatric symptoms are common in African-American vascular dementia patients, and cognitive impairment may be associated with psychiatric symptoms, behavioral problems, and personality changes. As there is a paucity of information about the prevalence of psychiatric symptoms in African Americans with vascular dementia, additional studies are needed to validate these findings. A better understanding of psychiatric symptoms in vascular dementia could lead to improved diagnosis and treatment of this disorder.
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PMID:Psychiatric symptoms in dementia associated with stroke: a case-control analysis among predominantly African-American patients. 796 34

Sleep problems in older adults are so common that nearly half of all hypnotic prescriptions written are for persons over 65 years old. Although normal aging affects sleep, the practitioner should evaluate the many factors that cause insomnia: medical illness, psychiatric illness, dementia, alcohol and/or polypharmacy, restless legs syndrome, periodic leg movements, and sleep apnea syndrome. Nonpharmacologic treatment of sleep disorders is preferred. The nurse practitioner can assess and manage elderly patients with sleep disorders, but they need to refer those who can benefit from evaluation to a sleep disorder center.
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PMID:Sleep problems in the elderly. 800 65


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