Cognitive symptoms of Alzheimer’s disease: clinical management and prevention

BMJ ◽  
2019 ◽  
pp. l6217 ◽  
Author(s):  
Elizabeth Joe ◽  
John M Ringman

ABSTRACTAlzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid β in the form of extracellular plaques and by intracellular neurofibrillary tangles, with eventual neurodegeneration and dementia. There is currently no disease-modifying treatment though several symptomatic medications exist with modest benefit on cognition. Acetylcholinesterase inhibitors have a consistent benefit across all stages of dementia; their benefit in mild cognitive impairment and prodromal AD is unproven. Memantine has a smaller benefit on cognition overall which is limited to the moderate to severe stages, and the combination of a cholinesterase inhibitor and memantine may have additional efficacy. Evidence for the efficacy of vitamin E supplementation and medical foods is weak but might be considered in the context of cost, availability, and safety in individual patients. Apparently promising disease-modifying interventions, mostly addressing the amyloid cascade hypothesis of AD, have recently failed to demonstrate efficacy so novel approaches must be considered.

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.


2000 ◽  
Vol 2 (2) ◽  
pp. 101-110 ◽  

Alzheimer's disease (AD) is a disorder of two pathologies- plaques and tangles. The former have as a key constituent amyloid protein and the latter the microtubule-associaied protein tau. Genetics has demonstrated that changes in either protein are sufficient to cause dementia. The amyloid cascade hypothesis proposes that plaque-related changes precede tangle-related changes and positions amyloid as central to the degeneration of AD. All the evidence suggests this is correct, including evidence that presenil ins alter the processing of the amyloid precursor protein and evidence that disrupting the normal properties of tau underlies the related froniotemporal dementias. The amyloid cascade hypothesis has provided the basis for nearly a decade of intensive basic science - the skeleton of that hypothesis can now be fleshed out, and confidence is growing that this will result in useful disease-modifying therapies in the future.


2021 ◽  
pp. 107385842110164
Author(s):  
Isabela F. L. Mota ◽  
Larissa S. de Lima ◽  
Bruna de M. Santana ◽  
Giovanna de A. M. Gobbo ◽  
João V. M. L. Bicca ◽  
...  

Alzheimer’s disease (AD) is the main cause of dementia in the world and its etiology is not yet fully understood. The pathology of AD is primarily characterized by intracellular neurofibrillary tangles and extracellular amyloid-β plaques. Unfortunately, few treatment options are available, and most treat symptoms, as is the case of acetylcholinesterase inhibitors (IAChE) and N-methyl-d-aspartate receptor antagonists. For more than 20 years pharmaceutical research has targeted the “amyloid cascade hypothesis,” but this has not produced meaningful results, leading researchers to focus now on other characteristics of the disease and on multitarget approaches. This review aims to evaluate some new treatments that are being developed and studied. Among these are new treatments based on peptides, which have high selectivity and low toxicity; however, these compounds have a short half-life and encounter challenges when crossing the blood-brain barrier. The present review discusses up-and-coming peptides tested as treatments and explores some nanotechnological strategies to overcome the downsides. These compounds are promising, as they not only act on the symptoms but also aim to prevent progressive neuronal loss.


2020 ◽  
Vol 74 (4) ◽  
pp. 1309-1317 ◽  
Author(s):  
Timothy Daly ◽  
Marion Houot ◽  
Anouk Barberousse ◽  
Yves Agid ◽  
Stéphane Epelbaum

2020 ◽  
Vol 21 (3) ◽  
pp. 884 ◽  
Author(s):  
Youngjae Jeon ◽  
Jae Ha Lee ◽  
Byoungyun Choi ◽  
So-Yoon Won ◽  
Kyoung Sang Cho

Alzheimer’s disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to abnormal accumulation of the amyloid β (Aβ) protein. Despite decades of intensive research, the mechanisms underlying AD remain elusive, and the only available treatment remains symptomatic. Molecular understanding of the pathogenesis and progression of AD is necessary to develop disease-modifying treatment. Drosophila, as the most advanced genetic model, has been used to explore the molecular mechanisms of AD in the last few decades. Here, we introduce Drosophila AD models based on human Aβ and summarize the results of their genetic dissection. We also discuss the utility of functional genomics using the Drosophila system in the search for AD-associated molecular mechanisms in the post-genomic era.


Author(s):  
Prativa Sadhu ◽  
◽  
Srijani Sen ◽  
Catherine Vanlalhriatpuii ◽  
◽  
...  

Neurodegenerative disorders are marked by the loss of brain neuron activity, resulting in gradual cognitive impairment. The effects of neurodegenerative diseases are severe in terms of pathology and the cost of patient care. The aged, in general, are the most vulnerable. Alzheimer's disease (AD) is a brain ailment that causes cell degradation and is the leading cause of dementia, identified by a loss of thinking ability and independence in daily tasks. The amyloid cascade hypothesis, which attributes clinical signs/symptoms to an abundance of amyloid-beta (Aβ) peptides, enhanced deposition into amyloid plaques, and eventually neuronal destruction, is one theory for pathogenesis AD. The use of acetylcholinesterase inhibitors in AD treatment is based on their favorable effects on the disease's functional, cognitive and behavioral symptoms. However, their involvement in AD pathogenesis is uncertain. This comprehensive review will provide an overview of AD, including the pathophysiology, causes, treatments, and future treatment.


Sign in / Sign up

Export Citation Format

Share Document