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[Anti-dementia drugs for Alzheimer disease in present and future].

Alzheimer disease(AD) is characterized as neurodegenerative disease showing impairment of cognitive function, death of neuronal cells, numerous numbers of senile plaques and tangle of neurofilaments. There are two different hypotheses that neurotoxicity of aggregated amyloid beta protein(A beta) and hyperphosphorylation of tau protein are the causes of AD. The dysfunction of cholinergic neuronal system is observed in the early stage of AD. Therefore, the strategy to increase of acetylcholine (ACh) level in brain by using ACh esterase inhibitor is mainstream in the present. We have tacrine, donepezil, rivastigmine and galantamine. Tacrine, the first drug for AD, is replaced by other drugs, because of its hepatic toxicity. Galantamine binds allosteric sites of nicotine receptor and stimulates it in addition to its inhibitory effect on ACh esterase. Metamantine was approved in EU in 2002. It is non-competitive inhibitor of NMDA receptors, and dopamine releaser, which has neuroprotective effect. All of the above drugs improve cognitive function of patients, and they could delay hospitalization for 7 months or more. In the present anti-inflammatory drugs, anti-oxidative drugs and estrogen are under investigation. As anti-A beta therapy, inhibitors of beta -and gamma-secretase, A beta aggregation inhibitors, A beta degradation stimulators and A beta vaccination are possible strategies. The inhibitors of tau protein phosphorylation and activators of phosphates could be that of anti-tau protein phosphorylation. Additionally, it is expected to have the strategies such as neuroregeneration by neurotorophic factors and immunopyline ligands, and supply of neuronal cells by gene therapy and human ES cells.

Acetylcholine↗

Alzheimer's disease: emerging noncholinergic treatments.

With population trends skewing toward a larger percentage of elderly, Alzheimer's disease is projected to afflict many millions in the United States and around the world in the next 50 years. In terms of cost and psychological burden, the anticipated burden of this disease on caregivers and society at large is staggering. It is hoped that, with the development of new insights into the processes of this devastating illness and the development of new medications that may interrupt those processes, the projected incidence and impact of AD may be modified in the near future.

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[Early diagnosis and treatment of Alzheimer's disease. Implementation in the doctor's office].

The efficacy of antidemential agents proven in comprehensive studies and by clinical experience, now justifies an active and positive approach by the general physician to the diagnosis and treatment of patients with dementia. The proposals on how to implement diagnostic and therapeutic measures in the doctor's office comply both with medical quality criteria and the requirements for appropriateness of treatment and considerations of economy stipulated by German law. They therefore provide the basis for a modern diagnostic work-up and treatment strategy, which will also meet economical demands.

Aged↗

Therapy of Morbus Parkinson and radical-induced neurotoxicity in the rat--in vivo voltammetric studies.

In vivo pulse voltammetry was used to study the effect of anti-parkinsonian drugs and of neurotoxins in rat striatum. It could be demonstrated that besides the well-known changes of total dopamine (DA) concentrations the applied drugs affected also the extraneuronal DA metabolism in the living rat. In addition, neurotoxin-treated rats can be used as a model to study some aspects of the Parkinson syndrome.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The search for better noncholinergic treatment options for Alzheimer's disease.

Alzheimer's disease is a biological process that involves the disruption of multiple neurochemical pathways. Current treatments for Alzheimer's disease focus on deficits in the cholinergic neurochemical pathway. While newer generation cholinergic agents have a more favorable side effect profile, only a limited, but consistent, degree of efficacy is seen. Treatments are emerging that focus on other areas of neurochemical activity such as oxidative damage, inflammation, glutamatergic neurotransmissions, and serotonergic and dopaminergic pathways. These treatments, supplemented with current cholinergic therapies, may help to ease patients' suffering and caregiver distress.

Alzheimer Disease↗

The influence of antiserotonergic agents on the action of dopaminergic drugs.

The effect of drugs blocking serotonin receptors: cyproheptadine, methysergide, and methergoline, and of serotonin synthesis inhibitor, p-chlorophenylalanine on the stereotyped behavior and number of rearings of the rats receiving apomorphine, amphetamine, nomifensine and 1,3-dimethyl-5-aminoadamantane was investigated. The blockade of serotonin receptors potentiates behavioral effects of dopamine agonists. It is concluded that central serotonin may play an inhibitory role, antagonistic to that of catecholamines.

Animals↗

[Current therapy of patients with dementia].

In recent years, the efficacy of symptomatic treatment in patients with Alzheimer's disease has repeatedly been demonstrated in a number of multicenter studies. Such treatment aims both to improve the patient's cognitive abilities and to preserve his or her quality of life and ability to cope with the activities of daily life. In this way the burden on relatives and caregivers is reduced, and the need for home or institutionalized care delayed. Causally effective therapeutic strategies resulting in a cure or the delaying of pathophysiological progression are currently not available, but are being investigated in ongoing clinical and experimental studies. Presently available treatments should be initiated early on, and applied as long as needed, which requires the earliest possible clinical diagnosis by the primary-care physician. The results of initial studies reveal an effect of antidementia agents also in mixed Alzheimer's and vascular dementia, as well as vascular and lewy-body dementia. Efforts to obtain approval for these indications are underway.

Activities of Daily Living↗

Diagnosis and management of Alzheimer's disease.

Alzheimer's disease is a progressive neurological condition that usually presents with short-term memory impairment, and then progresses to profound cognitive and physical disability. The diagnosis is based primarily on clinical findings with a definitive diagnosis only being possible with pathological examination of brain tissue. Alzheimer's disease causes distress to patients, families and caregivers. Most patients with advanced Alzheimer's disease need 24-hour supervision, often provided in a long-term care setting. Although no cure is available, with a variety of treatments, modest but measurable benefits are available. Research is being conducted to find more effective treatments and hopefully in time a cure or means of prevention. All physicians whose practice includes older patients need to possess some familiarity with the diagnosis and management of Alzheimer's disease.

Aged↗