Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Management of the most common type of dementia--Alzheimer's disease--is becoming increasingly sophisticated. Differentiation of Alzheimer's disease from vascular dementia has become therapeutically important, since the choice of treatments depends on the diagnosis. Two cholinesterase inhibitors, donepezil and tacrine, are labeled for use in patients with Alzheimer's disease. Other therapies, such as estrogen, nonsteroidal anti-inflammatory drugs and vitamin E, are sometimes used and show promise in delaying the progression of this dementia. Behavior problems, which often accompany the disease, can be managed using environmental modification, alterations in caregiving and medication. In the terminal phase of the illness, quality care involves implementing advance directives, communicating with the family, individualizing care and attending to patient comfort.
...
PMID:Advances in the treatment of Alzheimer's disease. 982 56

Alzheimer's disease (AD) is characterized in the brain by the deposition of amyloid protein outside the neuron, resulting in the formation of plaques, and inside the neuron with neurofibrillary tangles. It is not yet known what causes these pathologic changes, although age and genetics are major risk factors. The cholinesterase inhibitors tacrine and donepezil block acetylcholinesterase and therefore preserve the neurotransmitter acetylcholine. Three other investigational cholinesterase inhibitors are rivastigmine, metrifonate, and galanthamine. Existing therapies being studied for use in AD include vitamin E, estrogen preparations, and anti-inflammatory agents. The physician's role is to care for both the AD patient and the family, which are profoundly affected by this disease.
...
PMID:Alzheimer's disease: seeking new ways to preserve brain function. Interview by Alice V. Luddington. 1002 72

Previous experimental data indicate the involvement of Ca(2+)-related excitotoxic processes, possibly mediated by N-Methyl-D-Aspartate (NMDA) receptors, in beta-amyloid (beta A) neurotoxicity. On the other hand, other lines of evidence support the view that free radical generation is a critical step in the beta A-induced neurodegenerative cascade. In the present study, therefore, a neuroprotective strategy was applied to explore the contributions of each of these pathways in beta A toxicity. beta A(1-42) was injected into the magnocellular nucleus basalis of rats, while neuroprotection was achieved by either single or combined administration of the NMDA receptor antagonist MK-801 (2.5 mg/kg) and/or a vitamin E and C complex (150 mg/kg). The degree of neurodegeneration was determined by testing the animals in consecutive series of behavioral tasks, including elevated plus maze, passive avoidance learning, small open-field and open-field paradigms, followed by acetylcholinesterase (AChE), choline-acetyltransferase (ChAT), and superoxide dismutase (SOD) biochemistry. beta A injected in the nucleus basalis elicited significant anxiety in the elevated plus maze, derangement of passive avoidance learning, and altered spontaneous behaviors in both open-field tasks. A significant decrease in both AChE and ChAT accompanied by a similar decrement of MnSOD, but not of Cu/ZnSOD provided neurochemical substrates for the behavioral changes. Each of the single drug administrations protected against the neurotoxic events, whereas the combined treatment failed to ameliorate beta A toxicity.
...
PMID:N-Methyl-D-aspartate receptor antagonist MK-801 and radical scavengers protect cholinergic nucleus basalis neurons against beta-amyloid neurotoxicity. 1034 26

PURPOSE: To monitor progression of cerebral blood flow deterioration, this study used consecutive surface SPECT to evaluate the feasibility of brain surface displays (BSD) to follow Alzheimer's disease (AD) to determine whether overtime is a consistent feature of the disease. METHODS: Eighteen men (mean age, 75.7 years) with probable Alzheimer's disease (AD), with moderate to profound dementia indicated by the Mini-Mental State Examination (MMSE; median score, 10; range, 0 to 19), underwent brain Tc-99m ethyl cysteinate dimer SPECT. Brain SPECTs were obtained using a three-head gamma camera. Brain surface displays (BSD) were reconstructed from transaxial data using a threshold of 55% of the maximum pixel count. A second series of SPECTs were obtained after 5 to 23 months (except for one, which was done after 60 months). Each BSD was graded semiquantitatively, by visual interpretation, from zero to 8 (normal = 0, mild = 2, moderate = 4, severe = 6, and profound = 8) depending on the extent of the perfusion defects in the frontal, temporal, or parietal (or all of these) pattern of AD. MMSE scores were used to calculate "time index" values for estimating severity at the time of the SPECTs. RESULTS: The initial BSD scores correlated significantly with dementia severity (r = 0.71, P < 0.001). All 18 patients had decreased blood flow on consecutive SPECTs. Scores for BSD progressed at a rate of 2.5 +/- 1.7 points per year and correlated significantly with the time interval between the scans (r = 0.71; P < 0.001). CONCLUSIONS: The BSDs of SPECT scan data have considerable objective discriminatory power for assessing the severity and progression of AD-related hypoperfusion, particularly in the moderate to profound dementia ranges, and is potentially more reliable than the MMSE. Consecutive BSDs simplify SPECT image interpretation for measuring loss of brain function over time and could be useful for assessing the efficacy of therapeutic interventions for AD patients such as vitamin E and cholinesterase inhibitors.
...
PMID:Consecutive brain SPECT surface three-dimensional displays show progression of cerebral cortical abnormalities in Alzheimer's disease 1051 3

This paper sets a research agenda for the prediction and prevention of future onset of Alzheimer's disease (AD). From a MEDLINE review of the literature, the authors found age to be a predictor of AD. The literature also indicates that memory and attentional impairments predict AD, although the relative risk is relatively low. Late-onset depression may also predict AD, but these data are limited by a lack of cohort studies. Studying cognitively impaired subjects with late-onset depression may identify a high-risk group, facilitating prevention trials. Characteristics of an "ideal" preventive agent are suggested. There is a biologic rationale, and preliminary evidence, that non-steroidal anti-inflammatory drugs (including ASA), estrogen and vitamin E may play a preventive role in AD. Other compounds (such as acetylcholinesterase inhibitors) are also promising, but costs, side effects, and lack of other health benefits may preclude their use in all but very high-risk groups.
...
PMID:The prediction and prevention of Alzheimer's disease--towards a research agenda. 1058 31

Alzheimer disease (AD) involves neuronal degeneration with impaired cholinergic transmission in the cerebral cortex and hippocampus in areas of the brain particularly associated with memory and higher intellectual functioning. Other neurotransmitter deficits also occur, but the mechanisms underlying the widespread impairment of synaptic functions remain uncertain. Research on the molecular basis of AD has elucidated a pathogenic pathway from which a range of rational pharmacological interventions has emerged. Although at least 3 cholinesterase inhibitors (tacrine hydrochloride, donepezil, and rivastigmine tartrate) are now available and provide patients with modest relief, the most promising strategy involves approaches to retarding, halting, or preventing the formation or accumulation of beta-amyloid (Abeta) plaques. Estrogen is believed to have antioxidant or other anti-Abeta effects, as hormonal replacement therapy in women with menopause is associated with a reduced risk or delayed onset of AD. The association between nonsteroidal anti-inflammatory drugs and a reduced risk of AD has not yet been confirmed, but these agents may protect the brain from the reactive glial and microglial responses associated with Abeta deposition. Also, recent studies suggested that antioxidants, such as vitamin E taken alone or in combination with selegiline hydrochloride, can delay the progression of AD. Despite these encouraging results, no current therapy has been shown to halt or reverse the underlying disease process. The proof of the principle that anti-Abeta drugs will work in the transgenic models of AD is eagerly awaited with the expectation that they will eventually prove successful in humans.
...
PMID:Prospects for pharmacological intervention in Alzheimer disease. 1076 17

At present pharmacotherapy of Alzheimer's disease (AD) is limited to acetylcholinesterase inhibitors. These drugs produce small, but consistent improvements of memory and global function, some are also positively influencing activities of daily living. This therapeutic approach neglects the complexity of AD and the fact that most of the degenerating neurons are not cholinergic. Acetylcholinesterase inhibitors are symptomatic drugs, with no influence on disease progression. There is a need for disease modifying compounds, or preventive drugs. Data are indicating that vitamin E has some ability to influence the disease progression. The potency of non-steroidal anti-inflammatory drugs (NSAIDs) or estrogen as preventive agents has to be explored further in prospective clinical studies. The initial hope in the use of naturally occurring neurotrophic factors, like nerve growth factor, to rescue cholinergic neurons from degeneration and to restore cognitive function has been disappointed in first, small clinical studies. The peptidergic drug Cerebrolysin exhibiting neurotrophic stimulation, neuroimmunotrophic regulation and induction of BBB glucose transporter expression, might be able to address the pathological changes of AD at different levels simultaneously. In addition to an impressive preclinical database, results from 3 placebo-controlled, double-blind studies demonstrate significant improvements of cognitive performance, global function and activities of daily living in AD patients. In all studies persisting improvements, up to 6 months after drug withdrawal, indicate a powerful disease modifying activity.
...
PMID:Approach towards an integrative drug treatment of Alzheimer's disease. 1096 42

Use of valid diagnostic criteria is extremely important in the recognition of Alzheimer's disease (AD). Patients with mild to moderate Alzheimer's disease should be started on a cholinesterase inhibitor and possibly anti-inflammatory agents, antioxidants (vitamin E or selegiline), and estrogen replacement therapy (for postmenopausal women). Close follow-up of functioning is needed to be able to provide symptomatic relief and possibly slow down the progression of the disease. Comorbid medical conditions as well as superimposed psychiatric disturbances should be aggressively treated. Pharmacologic interventions and environmental engineering (including support for family members) should be used throughout the course of the disease. Genetic testing is not recommended in asymptomatic family members considering the enormous potential for job and insurance discrimination.
...
PMID:Alzheimer's Disease. 1109 36

Comprehensive treatment of Alzheimer's disease (AD) requires thorough caregiver support and a thoughtful and informed use of medications for cognition enhancement, neuroprotection, and the treatment of disturbed behavior. Current treatments such as the cholinesterase inhibitors donepezil and rivastigmine can slow the progression of cognitive and functional deficits in AD over the short term. Sustained improvement and possible disease modification that result from the use of these medications are being evaluated in long-term studies. Treatment with alpha-tocopherol (vitamin E) has been shown to delay the progression of nursing home admission in patients with mild-to-moderate AD. Although antioxidant, anti-inflammatory, and other treatment strategies are promising, recent studies of the treatment of AD with estrogen or prednisone have produced disappointing results. For managing the behavioral symptoms that commonly accompany AD (e.g., delusions, aggression, depression, anxiety, irritability), various antipsychotics, antidepressants, and anticonvulsants have been effective in carefully selected patients.
...
PMID:Alzheimer's disease: clinical treatment options. 1114 77

The latency of P300 "cognitive" event-related potentials changes if cholinergic activities of the central nervous system are pharmacologically manipulated. We tested the hypothesis that the new cholinesterase inhibitors donepezil (DPZ) and rivastigmine (Riv) may have an effect on the frequently abnormal P300 component in patients with Alzheimer disease (AD), thereby allowing a significant evaluation of cholinesterase inhibitors. We evaluated 60 patients with mild to moderately severe probable AD, in comparison with 60 age-matched control subjects, with P300 recordings and neuropsychologic examinations. Forty patients were randomly assigned in a double-blinded trial to 5-10 mg/d DPZ versus 2,000 IU/d vitamin E, and 20 patients were instead treated in an open trial with 1.5 to 12 mg/d Riv. In patients treated with vitamin E, we observed latency increments (7.4 +/- 3.5 msec) correlated with worsening neuropsychologic test scores. In patients treated with DPZ and Riv, we found significant P300 latency reductions (15.3 +/- 3.2 msec and 22.0 +/- 3.3 msec). Shorter P300 latencies were associated with higher Wechsler Adult Intelligence Scale scores and with lower AD Assessment Scale-cognitive subscale (ADAS-cog) scores (R = 0.72). Correlations between ADAS-cog changes and P300 changes significantly separated patients treated with DPZ and Riv from those treated with vitamin E. Administration of DPZ and Riv reduced the latencies of P300 components proportionately to neuropsychologic test improvements. Combined P300 and neuropsychologic test evaluation significantly separated DPZ-treated patients and Riv-treated patients from vitamin E-treated patients.
...
PMID:Donepezil, rivastigmine, and vitamin E in Alzheimer disease: a combined P300 event-related potentials/neuropsychologic evaluation over 6 months. 1129 Aug 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---