Pharmacological treatment of Alzheimer disease.
ABSTRACT To review the different pharmacological approaches to the cognitive, functional, and behavioural manifestations of Alzheimer disease (AD).
We searched and critically analyzed the most recent relevant literature on pharmacological treatment of AD.
The current pharmacological approach to AD treatment is based on vascular prevention and symptomatic therapy with cholinesterase inhibitors (ChEIs) and memantine, an N-methyl-d-aspartic acid antagonist. Clinical trials of 6- to 12-month duration have shown statistically significant benefits with ChEIs and memantine on cognitive, global, functional, and behavioural outcome measures. In general, these benefits are modest. However, they are dose-dependent and reproducible across studies. Most importantly, these benefits are symptomatic as they do not alter disease course. According to the third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, these agents are considered standard treatment options in AD. We will discuss practical issues related to current pharmacological management, such as setting realistic expectations, management of side effects, switching ChEIs, and the decision to discontinue treatment. The results of clinical trials studying potentially disease-modifying approaches in AD will also be reviewed. Unfortunately, although there remains much promise and enthusiasm, none of these agents has shown consistent benefits, and none are available for use in clinical practice.
Pharmacological options are presently available for the symptomatic treatment of AD. These treatments provide mild but sustained benefits. Before disease-modifying approaches become available, optimizing the use of the available treatment options is crucial.
- SourceAvailable from: Siddhartha Mondragon-Rodriguez[show abstract] [hide abstract]
ABSTRACT: Glycogen synthase kinase 3 (GSK3) has been implicated in neurological disorders; therefore, it is not surprising that there has been an increased focus towards developing therapies directed to this kinase. Unfortunately, these current therapies have not taken into consideration the physiological role of GSK3 in crucial events like synaptic plasticity. With this in mind we will discuss the relationship of synaptic plasticity with GSK3 and tau protein and their role as potential targets for the development of therapeutic strategies. Finally, we will provide perspectives in developing a cocktail therapy for Alzheimer's treatment.International journal of Alzheimer's disease. 01/2012; 2012:276803.
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ABSTRACT: Inhibitors of acetylcholine breakdown by acetylcholinesterase (AChE) constitute the main therapeutic modality for Alzheimer's disease. In the search for natural products with inhibitory action on AChE, this study investigated the activity of saffron extract and its constituents by in vitro enzymatic and molecular docking studies. Saffron has been used in traditional medicine against Alzheimer's disease. Saffron extract showed moderate AChE inhibitory activity (up to 30%), but IC(50) values of crocetin, dimethylcrocetin, and safranal were 96.33, 107.1, and 21.09 μM, respectively. Kinetic analysis showed mixed-type inhibition, which was verified by in silico docking studies. Safranal interacts only with the binding site of the AChE, but crocetin and dimethylcrocetin bind simultaneously to the catalytic and peripheral anionic sites. These results reinforce previous findings about the beneficial action of saffron against Alzheimer's disease and may be of value for the development of novel therapeutic agents based on carotenoid-based dual binding inhibitors.Journal of Agricultural and Food Chemistry 06/2012; 60(24):6131-8. · 2.91 Impact Factor
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ABSTRACT: Increasing evidence is emerging that vascular disease and its risk factors play a role in the development of Alzheimer's disease (AD) and affect the probability of an adverse outcome. The aims of this review are to explore the relationship between vascular risk factors and AD and to discuss the potential use of vascular markers in the clinical approach to cognitive impairment. Moreover, we present evidence about the potential use of ultrasonographic and neuroradiologic markers of cognitive impairment in order to establish possible treatment strategies in subjects with a clinical profile at risk of developing AD.Journal of Alzheimer's disease: JAD 08/2012; · 4.17 Impact Factor