scholarly journals Therapies for Prevention and Treatment of Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
J. Mendiola-Precoma ◽  
L. C. Berumen ◽  
K. Padilla ◽  
G. Garcia-Alcocer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitors ◽  
Pharmacological Treatments ◽  
Blood Brain Barrier Disruption ◽  
Important Health ◽  
Brain Barrier Disruption ◽  
Important Health Issue ◽  
Nonpharmacological Treatments

Alzheimer’s disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-βpeptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists and etiology-based treatments such as secretase inhibitors, amyloid binders, and tau therapies. Strategies for prevention of AD through nonpharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. AD is an important health issue on which all people should be informed so that prevention strategies that minimize the risk of its development may be implemented.

scholarly journals The effect of insomnia on development of Alzheimer’s disease

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Shaghayegh Sadeghmousavi ◽  
Mahsa Eskian ◽  
Farzaneh Rahmani ◽  
Nima Rezaei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Potential Role ◽  
Neurodegenerative Disorder ◽  
Memory Deficits ◽  
Information Recall ◽  
Important Health ◽  
Important Health Issue

Abstract Alzheimer’s disease (AD) is the most common type of dementia and a neurodegenerative disorder characterized by memory deficits especially forgetting recent information, recall ability impairment, and loss of time tracking, problem-solving, language, and recognition difficulties. AD is also a globally important health issue but despite all scientific efforts, the treatment of AD is still a challenge. Sleep has important roles in learning and memory consolidation. Studies have shown that sleep deprivation (SD) and insomnia are associated with the pathogenesis of Alzheimer’s disease and may have an impact on the symptoms and development. Thus, sleep disorders have decisive effects on AD; this association deserves more attention in research, diagnostics, and treatment, and knowing this relation also can help to prevent AD through screening and proper management of sleep disorders. This study aimed to show the potential role of SD and insomnia in the pathogenesis and progression of AD.

Oxidative Stress Targeting Amyloid Beta Accumulation and Clearance in Alzheimer’s Disease: Insight into Pathological Mechanisms and Therapeutic Strategies

2020 ◽  
Vol 9 (1) ◽  
pp. 22-42
Author(s):  
Sunpreet Kaur ◽  
Puneet Kumar ◽  
Shamsher Singh
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitors ◽  
The Elderly ◽  
Biochemical Alterations ◽  
App Trafficking ◽  
Copper Aluminum

Background: Alzheimer’s disease is the most common neurodegenerative disorder affecting the elderly population and emerges as a leading challenge for the scientific research community. The wide pathological aspects of AD made it a multifactorial disorder and even after long time it’s difficult to treat due to unexplored etiological factors. Methods: The etiogenesis of AD includes mitochondrial failure, gut dysbiosis, biochemical alterations but deposition of amyloid-beta plaques and neurofibrillary tangles are implicated as major hallmarks of neurodegeneration in AD. The aggregates of these proteins disrupt neuronal signaling, enhance oxidative stress and reduce activity of various cellular enzymes which lead to neurodegeneration in the cerebral cortex, neocortex and hippocampus. The metals like copper, aluminum are involved in APP trafficking and promote amyloidbeta aggregation. Similarly, disturbed ubiquitin proteasomal system, autophagy and amyloid- beta clearance mechanisms exert toxic insult in the brain. Result and conclusion : The current review explored the role of oxidative stress in disruption of amyloid homeostasis which further leads to amyloid-beta plaque formation and subsequent neurodegeneration in AD. Presently, management of AD relies on the use of acetylcholinesterase inhibitors, antioxidants and metal chelators but they are not specific measures. Therefore, in this review, we have widely cited the various pathological mechanisms of AD as well as possible therapeutic targets.

scholarly journals In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors Against Alzheimer’s Disease

2018 ◽  
Vol 17 (1) ◽  
pp. 54-68 ◽  
Author(s):  
Kanzal Iman ◽  
Muhammad Usman Mirza ◽  
Nauman Mazhar ◽  
Michiel Vanmeert ◽  
Imran Irshad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Neurodegenerative Disorder ◽  
In Silico Analysis ◽  
Acetylcholinesterase Inhibitors ◽  
Binding Energies ◽  
Therapeutic Interventions ◽  
Ache Inhibitors

Objective and Background: Inhibition of acetylcholinesterase (AChE) has gained much importance since the discovery of the involvement of peripheral anionic site as an allosteric regulator of AChE. Characterized by the formation of β-amyloid plaques, Alzheimer's disease (AD) is currently one of the leading causes of death across the world. Progression in this neurodegenerative disorder causes deficit in the cholinergic activity that leads towards cognitive decline. Therapeutic interventions in AD are largely focused upon AChE inhibitors designed essentially to prevent the loss of cholinergic function. The multifactorial AD pathology calls for Multitarget-directed ligands (MTDLs) to follow up on various components of the disease. Considering this approach, other related AD targets were also selected. Structure-based virtual screening was relied upon for the identification of lead compounds with anti-AD effect. Method: Several chemoinformatics approaches were used in this study, reporting four multi-target inhibitors: MCULE-7149246649-0-1, MCULE-6730554226-0-4, MCULE-1176268617-0-6 and MCULE-8592892575-0-1 with high binding energies that indicate better AChE inhibitory activity. Additional in-silico analysis hypothesized the abundant presence of aromatic interactions to be pivotal for interaction of selected compounds to the acetyl-cholinesterase. Additionally, we presented an alternative approach to determine protein-ligand stability by calculating the Gibbs-free energy change over time. Furthermore, this allows to rank potential hits for further in-vitro testing. Results and Conclusion: With no predicted indication of adverse effects on humans, this study unravels four active multi-target inhibitors against AChE with promising affinities and good ADMET profile for the potential use in AD treatment.

scholarly journals Deficiency in Mural Vascular Cells Coincides with Blood-Brain Barrier Disruption in Alzheimer's Disease

2012 ◽  
Vol 23 (3) ◽  
pp. 303-310 ◽  
Author(s):  
Jesse D. Sengillo ◽  
Ethan A. Winkler ◽  
Corey T. Walker ◽  
John S. Sullivan ◽  
Mahlon Johnson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Vascular Cells ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

scholarly journals Evaluación de una intervención logopédica en pacientes con la enfermedad de Alzheimer en tratamiento colinérgico: Un estudio piloto

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Miguel López-Zamora ◽  
Miriam Cánovas-Cano ◽  
Lourdes Aranda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Alzheimer Disease ◽  
Speech Therapy ◽  
Therapeutic Option ◽  
Acetylcholinesterase Inhibitors ◽  
Pharmacological Therapy ◽  
Cognitive Deterioration ◽  
Pharmacological Treatments

Abstract: Evaluation of a speech therapy in patients with Alzheimer's disease under cholinergic treatment: A pilot study. The intervention on Alzheimer's disease (AD) has shown that pharmacological treatments with acetylcholinesterase inhibitors are highly beneficial. There is not much evidence if other treatments are effective, because it is difficult to find patients who are not medicated. In the present study a logopedic intervention in patients with AD in the mild phase, with and without pharmacological treatment, was verified. The results show that logopedic intervention slows the deterioration of the disease. The combination of logopedic intervention and pharmacological therapy is confirmed as the therapeutic option that most benefits the patient, while patients who only received one of the treatments show a more pronounced cognitive deterioration. The conclusions indicate that the pharmacological approach is necessary but insufficient, and that a logopedic intervention may be an adequate and effective complement in AD.Keywords: Alzheimer disease; Speech therapy; Acetylcholinesterase inhibitors. Resumen: Al intervenir en pacientes con la enfermedad de Alzheimer (EA) se ha comprobado que los tratamientos farmacológicos con inhibidores de acetilcolinesterasa resultan altamente beneficiosos, pero existen pocas evidencias sobre la efectividad de otros tratamientos debido a que es difícil encontrar pacientes que no estén medicados. En el presente estudio piloto se comprueba la efectividad de una intervención logopédica en enfermos con EA en fase leve, con y sin tratamiento farmacológico. Los resultados muestran que la intervención logopédica frena el deterioro de la enfermedad. La combinación de intervención logopédica y terapia farmacológica es la opción terapéutica que más beneficios reporta al paciente, mientras que los enfermos que sólo recibieron uno de los tratamientos muestran un deterioro cognitivo más pronunciado. Las conclusiones indican que la aproximación farmacológica es necesaria pero insuficiente, y que una intervención logopédica puede ser un complemento adecuado y eficaz de la EA.Palabras clave: Enfermedad de Alzheimer; Intervención logopédica; Inhibidores de acetilcolinesterasa.  

Abstract WMP111: Stroke and Alzheimer’s Disease: Shared Mechanisms of Vascular Disruption

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Brandon Lucke-Wold ◽  
Aric Logsdon ◽  
Afroz Mohammad ◽  
Chris Adkins ◽  
Xuefang Ren ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Fold Increase ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
Texas Red

Recent evidence suggests that Alzheimer’s disease is a vascular disorder that can be accelerated by ischemic stroke. We propose that the underlying pathophysiology accelerating degenerative changes is due to blood brain barrier disruption following ischemia. A transient middle cerebral artery occlusion suture model was used in triple-transgenic AD mice and C57/Bl6 wild type controls. A separate triple-transgenic AD mice group was used for sham control. The middle cerebral artery was occluded for 1 hour followed by reperfusion. Mice were evaluated for sickness behavior and received a modified neurologic score. 5 hours after reperfusion, blood brain barrier tracers (Texas red, IcG, and AIB1) were injected i.v. into the femoral vein and allowed to circulate for 10 minutes. H&E, Cresyl Violet, and Thioflavin were used to stain sections of the brain for areas of degeneration. Images were obtained by quantitative fluorescent and bright-field microscopy. One-way ANOVA with Tukey’s post-hoc comparison was used to compare between groups. P<0.05 was considered statistically significant. A statistically significant difference between groups was seen for blood brain barrier permeability following ischemia and reperfusion. Triple-transgenic AD mice had a 2-fold increase in Texas red and a 4-fold increase in AIB1 at 5 hours after reperfusion. No significant differences were seen in the control groups. H&E staining revealed nuclear fragmentation, chromatolysis, and vacuolization in the ipsilateral cortex of the triple-transgenic AD mice exposed to stroke. Limited areas of necrosis were seen in the C57/Bl6 controls. A significant increase in thioflavin staining was seen post-stroke in the triple-transgenic AD mice. The amyloid distribution was perivascular and significantly increased compared to the triple-transgenic AD sham mice. Triple-transgenic AD mice had a worse sickness score (avg. 13) compared to C57/Bl6 controls (avg. 17). Stroke and Alzheimer’s disease share similar vascular mechanisms related to blood brain barrier disruption. We show that blood brain barrier disruption post-stroke accelerates degenerative changes. Targeting blood brain barrier disruption as a treatment approach may prove promising and warrants continued investigation.

Auditory Dysfunction in Alzheimer's Disease

2010 ◽  
Vol 15 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Sridhar Krishnamurti
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Care Setting ◽  
Neurodegenerative Disorder ◽  
Disease Process ◽  
Clinical Protocols ◽  
Speech Language Pathologist ◽  
Auditory Dysfunction

Alzheimer's disease is neurodegenerative disorder which affects a growing number of older adults every year. With an understanding of auditory dysfunction in Alzheimer's disease, the speech-language pathologist working in the health care setting can provide better service to these individuals. The pathophysiology of the disease process in Alzheimer's disease increases the likelihood of specific types of auditory deficits as opposed to others. This article will discuss the auditory deficits in Alzheimer's disease, their implications, and the value of clinical protocols for individuals with this disease.

Acetylcholinesterase Inhibitory Potential and Antioxidant Activities of Five Cultivars of Rosa Damascena Mill. From Isparta, Turkey

2020 ◽  
Vol 18 (4) ◽  
pp. 354-359
Author(s):  
Shirin Tarbiat ◽  
Azize Simay Türütoğlu ◽  
Merve Ekingen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radical ◽  
Neurodegenerative Disorder ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Acetylcholinesterase Activity ◽  
Rosa Damascena ◽  
Free Radical Damage

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impairment of language. Alzheimer's disease is strongly associated with oxidative stress and impairment in the cholinergic pathway, which results in decreased levels of acetylcholine in certain areas of the brain. Hence, inhibition of acetylcholinesterase activity has been recognized as an acceptable treatment against Alzheimer's disease. Nature provides an array of bioactive compounds, which may protect against free radical damage and inhibit acetylcholinesterase activity. This study compares the in vitro antioxidant and anticholinesterase activities of hydroalcoholic extracts of five cultivars of Rosa Damascena Mill. petals (R. damascena 'Bulgarica', R. damascena 'Faik', R. damascena 'Iranica', R. damascena 'Complex-635' and R. damascena 'Complex-637') from Isparta, Turkey. The antioxidant activities of the hydroalcoholic extracts were tested for ferric ion reduction and DPPH radical scavenging activities. The anti-acetylcholinesterase activity was also evaluated. All rose cultivars showed a high potency for scavenging free radical and inhibiting acetylcholinesterase activity. There was a significant correlation between antioxidant and acetylcholinesterase inhibitory activity. Among cultivars, Complex-635 showed the highest inhibitory effect with an IC50 value of 3.92 µg/mL. Our results suggest that all these extracts may have the potential to treat Alzheimer's disease with Complex-635 showing more promise.

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