Pharmacological treatment of Alzheimer’s disease

2017 ◽  
Author(s):  
Krishna Chinthapalli
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pharmacological Treatment ◽  
Daily Living ◽  
Disease Process ◽  
Acetylcholinesterase Inhibitors ◽  
Underlying Disease ◽  
Global Function ◽  
Glutamate Antagonist ◽  
The Brain

Pharmacological treatment of Alzheimer’s disease is an important part of management of the condition. There are only four drugs available for treatment of the disease and none halt the disease process, however they have a benefit on cognition, behaviour, activities of daily living, and global function. Acetylcholinesterase inhibitors are thought to work by enhancing cholinergic transmission in the brain and are particularly effective in mild and moderate AD, with recent evidence suggesting donepezil is also effective in severe AD. Memantine is the only glutamate antagonist that is available for AD and is limited for use in moderate or severe AD. The choice of drug depends on route of administration, adverse effects, and medical comorbidities. There is intense research on alternative treatments especially those that may stop the underlying disease process.

Measuring Disease Modification in Alzheimer's Disease

CNS Spectrums ◽  
2007 ◽  
Vol 12 (S1) ◽  
pp. 11-14
Author(s):  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immunoglobulin A ◽  
Disease Process ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Modification ◽  
Amyloid Disease ◽  
Therapeutic Modalities ◽  
Disease Modifying

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β -amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.

Introduction: Amyloid-Based Interventions in Alzheimer's Disease

CNS Spectrums ◽  
2007 ◽  
Vol 12 (S1) ◽  
pp. 2-3 ◽  
Author(s):  
Gary J. Kennedy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immunoglobulin A ◽  
Disease Process ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Amyloid Disease ◽  
Therapeutic Modalities ◽  
Reductase Inhibitors ◽  
Disease Modifying

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β-amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.

2',6'-dihydroxy-4'-methoxy dihydrochalcone improves the cognitive impairment of Alzheimer's disease: a structure-activity relationship study

2021 ◽  
Vol 21 ◽  
Author(s):  
Ana E. Gonçalves ◽  
Ângela Malheiros ◽  
Camila A. Cazarin ◽  
Lara de França ◽  
David L. Palomino-Salcedo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Acetylcholinesterase Inhibitors ◽  
Inhibitory Avoidance ◽  
Symptomatic Treatment ◽  
Memory Test ◽  
Object Recognition Test ◽  
Docking Simulations ◽  
The Brain

Background: Chalcones and dihydrochalcones present potent inhibition of acetylcholinesterase, which is currently considered the most efficient approach for symptomatic treatment of Alzheimer’s disease. Objective: The present study aimed to explore the potential benefits of 2',6'-dihydroxy-4'-methoxy dihydrochalcone on the cognitive deficits of animals submitted to the streptozotocin-induced Alzheimer's model, as well as to evaluate the possible mechanisms of action. Methods: Learning and memory functions of different groups of animals were submitted to the streptozotocin-induced Alzheimer's model (STZ 2.5 mg/mL, i.c.v.) and subsequently treated with 2',6'-dihydroxy-4'-methoxy dihydrochalcone (DHMDC) administered at doses 5, 15, and 30 mg/kg (p.o.), rivastigmine (0,6 mg/kg, i.p.) and vehicle were evaluated in aversive memory test (inhibitory avoidance test) and spatial memory test (object recognition test). Molecular docking simulations were performed to predict the binding mode of DHMDC at the peripheral site of AChE to analyze noncovalent enzyme-ligand interactions. DFT calculations were carried out to study well-known acetylcholinesterase inhibitors and DHMDC. Results: DHMDC markedly increased the learning and memory of mice. STZ caused a significant decline of spatial and aversive memories in mice, attenuated by DHMDC (15 and 30 mg/kg). Furthermore, STZ conspicuously increased lipid peroxidation and compromised the antioxidant levels in mice brains. DHMDC pretreatment significantly increased GSH activity and other oxidative stress markers and decreased TBARS levels in the brain of STZ administered mice. AChE activity was significantly decreased by DHMDC in the brain of mice. Conclusion: The results together point that DHMDC may be a useful drug in the management of dementia.

scholarly journals The Creatine Kinase/Creatine Connection to Alzheimer's Disease: CK Inactivation, APP-CK Complexes and Focal Creatine Deposits

2006 ◽  
Vol 2006 ◽  
pp. 1-11 ◽  
Author(s):  
Tanja S. Bürklen ◽  
Uwe Schlattner ◽  
Ramin Homayouni ◽  
Kathleen Gough ◽  
Margaret Rak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Creatine Kinase ◽  
Energy State ◽  
Energy Levels ◽  
Disease Process ◽  
Direct Interaction ◽  
Early Time ◽  
Cellular Energetics ◽  
The Brain

Cytosolic brain-type creatine kinase (BB-CK), which is coexpressed with ubiquitous mitochondrial uMtCK, is significantly inactivated by oxidation, in Alzheimer's disease (AD) patients. Since CK has been shown to play a fundamental role in cellular energetics of the brain, any disturbance of this enzyme may exasperate the AD disease process. Mutations in amyloid precursor protein (APP) are associated with early onset AD and result in abnormal processing of APP, and accumulation of Aβpeptide, the main constituent of amyloid plaques in AD brain. Recent data on a direct interaction between APP and the precursor of uMtCK support an emerging relationship between AD, cellular energy levels and mitochondrial function. In addition, recently discovered creatine (Cr) deposits in the brain of transgenic AD mice, as well as in the hippocampus from AD patients, indicate a direct link between perturbed energy state, Cr metabolism and AD. Here, we review the roles of Cr and Cr-related enzymes and consider the potential value of supplementation with Cr, a potent neuroprotective substance. As a hypothesis, we consider whether Cr, if given at an early time point of the disease, may prevent or delay the course of AD-related neurodegeneration.

A Clinical Overview of Cholinesterase Inhibitors in Alzheimer's Disease

2002 ◽  
Vol 14 (S1) ◽  
pp. 93-126 ◽  
Author(s):  
Martin Farlow
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Symptomatic Relief ◽  
Disease Process ◽  
Lewy Body Dementia ◽  
Underlying Disease ◽  
Research Experience ◽  
Behavioral Disturbances ◽  
The Individual ◽  
Che Inhibitors

This review provides an overview of the three most widely used cholinesterase (ChE) inhibitors: donepezil, rivastigmine, and galantamine. Differences in pharmacologic profiles will be discussed, and consideration will be given to how such differences may relate to and influence the clinical efficacy and tolerability of the various agents. In addition to providing cognitive benefits in patients with Alzheimer's disease (AD), growing clinical evidence also suggests that ChE inhibitors can produce favorable and clinically relevant effects on neuropsychiatric/behavioral disturbances and activities of daily living. Furthermore, recent data indicate that these agents may be effective at all levels of disease severity and for all rates of disease progression. The clinical utility of ChE inhibitors in a wider spectrum of dementias which share a common cholinergic deficit, such as Lewy body dementia, Parkinson's disease dementia, and vascular dementia, is currently under investigation. Beyond symptomatic relief, data suggest that ChE inhibitors may also slow the underlying disease process. As clinical and research experience with these agents continues to accumulate, the differences in their effects will become more apparent and will help physicians tailor ChE inhibition treatment to the needs of the individual patient.

Current insights into the pathophysiology of Alzheimer's disease: selecting targets for early therapeutic intervention

2012 ◽  
Vol 24 (S1) ◽  
pp. S10-S17 ◽  
Author(s):  
Harald Hampel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Investigation ◽  
Disease Process ◽  
Predictive Biomarkers ◽  
Underlying Disease ◽  
Disease Stage ◽  
Drug Candidates ◽  
Surrogate Outcome ◽  
Models Of Disease

ABSTRACTThe development of therapies for Alzheimer's disease (AD) presents numerous challenges for physicians, researchers, and the pharmaceutical industry, with many drug candidates showing promise at one stage of clinical research only to fall at the next hurdle. A great number of drugs with a variety of targets and clusters of mechanisms are currently in various stages of basic and clinical investigation. However, these hypothesis-derived agents may be tested much too late in the chronically progressive disease process to demonstrate meaningful effects or outcomes, mirroring the clinical syndromal scenario in which the underlying pathophysiological disease condition is frequently diagnosed extremely late. Moreover, the complexity of the disease calls for developments and improvements in study designs and methods modeled for different target populations and disease stages (e.g. asymptomatic to prodromal to syndromal). New integrated concepts and models of disease pathophysiology, use of validated and qualified biomarkers, outcomes and endpoints, particularly the development of a surrogate outcome, may allow targeting of characteristic mechanism-derived therapies of specifically affected biological systems at different time-points in the disease process, providing increasing opportunities for early and preventative intervention. A core set of feasible diagnostic and predictive biomarkers is already validated and in the process of standardization; however, continued and intensified research efforts will likely reveal a variety of novel biomarkers that grasp the complexity of the underlying disease process. In the future, trials of drugs to modify and prevent AD may embrace enrichment strategies and maybe be stratified by disease stage, genetic factors as well as by disease endophenotypes.

scholarly journals Natural products and their derived compounds inhibitors of the enzyme acetylcholinesterase

2020 ◽  
pp. 149-160
Author(s):  
Maha Z. Rizk ◽  
Hanan F. Aly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Secondary Metabolites ◽  
Plant Extracts ◽  
Elderly Population ◽  
Acetylcholinesterase Inhibitors ◽  
The Elderly ◽  
Neurodegenerative Pathology ◽  
The Brain

Alzheimer’s disease (AD) is a progressive, neurodegenerative pathology that primarily affects the elderly population, and is estimated to account for 50-60% of dementia cases in persons over 65 years of age. The main characteristics connected with AD implicate the dysfunction of cognitive role, mainly loss of memory. While, the main features linked with AD at later stages include deficits of language, depression and problems associated with behavior. One of the most important approaches for medication of this disease is to improve level of the acetylcholine in the brain tissues using inhibitors of acetylcholinesterase (AChE). The present work reviews the literature on natural products from plants and plant-derived compounds inhibitors of enzyme acetylcholinesterase. Keywords: Alzheimer’s disease; Acetylcholinesterase inhibitors; Secondary metabolites; Plant extracts; essential oils

scholarly journals The discovery of Alzheimer's disease

2003 ◽  
Vol 5 (1) ◽  
pp. 101-108 ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Severe Disease ◽  
Disease Process ◽  
South West ◽  
Alois Alzheimer ◽  
Memory Disturbance ◽  
The Brain ◽  
Clinical Psychiatrist ◽  
8Th Edition

On November 3, 1906, a clinical psychiatrist and neuroanatomist, Alois Alzheimer, reported "A peculiar severe disease process of the cerebral cortex" to the 37th Meeting of South-West German Psychiatrists in Tubingen, He described a 50-year-old woman whom he had followed from her admission for paranoia, progressive sleep and memory disturbance, aggression, and confusion, until her death 5 years later. His report noted distinctive plaques and neurofibrillary tangles in the brain histology. It excited little interest despite an enthusiastic response from Kraepelin, who promptly included "Alzheimer's disease" in the 8th edition of his text Psychiatrie in 1910. Alzheimer published three further cases in 1909 and a "plaque-only" variant in 1911, which reexamination of the original specimens in 1993 showed to be a different stage of the same process, Alzheimer died in 1915, aged 51, soon after gaining the chair of psychiatry in Breslau, and long before his name became a household word.

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