Pharmacological Interventions On Central Cholinergic Mechanisms In Senile Dementia Alzheimers Disease

The need for effective therapy to treat Alzheimer’s disease is greater than ever, but there is still no drug therapy that can stop or reverse the progression of the disease. There is, however, a great deal of anticipation over the imminent development of effective therapies as a result of the identification of promising targets for drug development. This book investigates these targets and examines ongoing strategies to develop effective therapies for this devastating neurodegenerative condition.

Alzheimer's disease is one the foremost health problems facing every society fortunate enough to attain a level of medical care that ensures an average lifespan of over 70 years of age. The cause of the disease remains unknown, and no single therapeutic approach has yet been found highly efficacious. Indeed, as the complexity of its effects on brain neuronal systems becomes elucidated, the concept emerges that Alzheimer's disease may be an umbrella term for multiple Alzheimer's-type syndromes that can be differentiated based on etiology (hereditary versus sporadic), neurochemical deficits, and extent of pathology. Whether one or more disease processes is involved, it seems increasingly unlikely that any single drug will provide efficacious relief across the broad spectrum of symptoms reflected in large subject populations. Rational therapeutic approaches may yield long term amelioration of many symptoms in selected groups of patients; and individual symptoms may be ameliorated in larger populations. Multiple approaches may be combined to optimize therapeutic effects. For example, a variety of approaches remain focused on restoration of cholinergic neurodegeneration and enhancing cholinergic neurotransmission, whereas other approaches attempt to retard the of the brain that occurs during Alzheimer's disease. Chapters cover continuous degeneration topics from growth factor secretion of proteases, which could modify amyloid processing, to neuronal gene delivery using viral vectors. The breadth and thoroughness of the chapters truly embrace a broad spectrurn of models, pathological mechanisms and therapeutic approaches.

Alzheimer’s disease is the most prevalent form of dementia. Although it was discovered about a century ago, the first drugs applied in treatment were only introduced in therapy in the last 30 years. This book focuses on the clinical pharmacology of drugs that aim to delay the progression of Alzheimer’s disease, such as anticholinesterases and glutamate receptor antagonists, as well as treatment for the behavioral changes caused by the progression of the disease: antidepressants, antipsychotics, anxiolytics, and mood stabilizers. In addition, it describes important information about the pathophysiology and diagnostic methods of Alzheimer’s disease, emergency situations conditioned by the dementia process, and presents new perspectives for the treatment of Alzheimer’s disease. The ten chapters cover topics such as mechanism of action, dosage regimen, adverse reactions, drug interactions, toxicity profiles, among other information of clinical relevance. The work comprises evidence-based studies, providing a valuable resource for analyzing, prescribing and monitoring patients being treated for Alzheimer’s disease. Written by experts with solid professional experience, this book will appeal to pharmacologists, geriatricians, neurologists, psychiatrists, biomedical clinicians, and other healthcare professionals.

Since the apoE4 allele is a risk factor or susceptibility gene in late-onset familial and sporadic AD, the mechanism of disease expression may involve metabolic effects that are isoform specific. Isoform-specific interactions of apoE therefore become critical in the mechanism of AD pathogenesis. Detailed characterization of the binding of the apoE isoforms with proteins and peptides relevant to the pathology of the disease may be critical in understanding disease pathogenesis. These critical isoform-specific interactions of apoE may involve interactions with proteins and pep tides in the defining neuropathologic lesions of the disease, the neurofibrillary tangle and senile plaque. Other possible critical isoform-specific interactions include the mechanism of internalization, intracellular trafficking, and subsequent metabolism. In addition, differential post-translational modifications of apoE isoforms may determine differences in metabolism contributing to the pathogenesis of the disease. Oxidation of apoE may confer several isoform-specific, biochemically distinct properties. Since {3A peptide binds apoE in the lipoprotein binding domain of the protein and not in the receptor-binding domain, apoE could target bound {3A4 peptide to neurons via the LRP receptor. Internalization of the apoEI {3A peptide complex into the cell, by the same route as the apoE-containing lipoproteins, would result in incorporation into primary lysosomes and pH dependent dissociation. The demonstration of apoE in the cytoplasm of neurons, with isoform-specific interactions of apoE with the microtubule-binding protein tau demonstrated in vitro, suggest additional, testable hypotheses of disease pathogenesis.

This thorough guide details clinical trials, the drugs currently available and the expectations of the doctor, family and carer

In this book, the four leading experts on the ACE inhibitors donepezil, galantamine, and rivastigmine and the NMDA receptor antagonist memantine explain the practical pharmacology of these symptomatic drugs with the aim of providing a sound basis for their clinical use in patients with Alzheimer’s disease. In addition, an introductory chapter considers the basic theory of pharmacology for Alzheimer’s disease and the book closes with an overview of the ways in which symptomatic drugs for dementia are used. The wide acceptance of the amyloid cascade hypothesis has led to vigorous development of disease-modifying drugs for Alzheimer’s disease, such as amyloid vaccinations and gamma- or beta-secretase inhibitors. The failure of clinical trials of these drugs to yield satisfactory results has, however, meant that for the time being patients continue to be treated only with symptomatic drugs. There is accordingly a need to become more proficient in the use of symptomatic medicines, and it is against the background of this quest that Practical Pharmacology for Alzheimer’s Disease will be of wide interest.

Frontiers in Clinical Drug Research - Alzheimer Disorders is a book series concerned with Alzheimer's disease (AD), a disease that causes dementia, or loss of brain function. This disease affects parts of the brain that affect memory, thought and language. Chapters in each volume focus on drug research with special emphasis on clinical trials, research on drugs in advanced stages of development and cure for Alzheimer’s disease and related disorders. Frontiers in Clinical Drug Research - Alzheimer Disorders will be of particular interest to readers interested in drug therapy of this specific neurodegenerative condition and related brain disorders as the series provides relevant reviews written by experts in the field of Alzheimer’s disease research. The eighth volume of this series features chapters covering critical discussions on new therapies for AD. The reviews in this volume include: - Novel Molecular Targets of Tauopathy; Therapeutic and Diagnostic Applications - The Therapy of Alzheimer’s Disease: Towards a New Generation of Drugs - Could Antibiotics Be Therapeutic Agents in Alzheimer’s Disease? - Use of Antipsychotics in Patients with Alzheimer’s Disease - Approaches Based on Cholinergic Hypothesis and Cholinesterase Inhibitors in the Treatment of Alzheimer's Disease - Potential Biological Mechanisms with Prophylactic Action in Rapid Cognitive Impairment in Late-Onset Alzheimer's Disease