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.  

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.

Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

2019 ◽  
Vol 15 (4) ◽  
pp. 373-382 ◽  
Author(s):  
Ralph C. Gomes ◽  
Renata P. Sakata ◽  
Wanda P. Almeida ◽  
Fernando Coelho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Population Aging ◽  
Acetylcholinesterase Inhibitors ◽  
Acetylcholinesterase Activity ◽  
Docking Study ◽  
Biological Properties ◽  
Ache Inhibitor ◽  
Molecular Docking Study

Background: The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease. Methods: The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase. Results: Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Conclusion: We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.

Different Morphology of Neuritic Plaques in the Archicortex of Alzheimer’s Disease with Comorbid Synucleinopathy: A Pilot Study

2020 ◽  
Vol 17 ◽  
Author(s):  
Nikol Jankovska ◽  
Tomas Olejar ◽  
Jaromir Kukal ◽  
Radoslav Matej
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Time Course ◽  
Clinical Course ◽  
Lewy Bodies ◽  
Dystrophic Neurites ◽  
Neuritic Plaques ◽  
Structural Differences ◽  
Lewy Body Variant

Background: Bulbous neuritic changes in neuritic plaques have already been described, and their possible effect on the clinical course of the disease has been discussed. OBJECTIVE: In our study, we focused on the location and density of these structures in patients with only Alzheimer’s disease (AD) and patients with AD in comorbidity with synucleinopathies. Methods: Utilizing immunohistochemistry and confocal microscopy, we evaluated differences of neocortical and archicortical neuritic plaques and the frequency of bulbous changes in the archicortex of 14 subjects with Alzheimer’s disease (AD), 10 subjects with the Lewy body variant of Alzheimer's disease (AD/DLB), and 4 subjects with Alzheimer's disease with amygdala Lewy bodies (AD/ALB). Also, the progression and density of neuritic changes over the time course of the disease were evaluated. Results: We found structural differences in bulbous dystrophic neurites more often in AD/DLB and AD/ALB than in pure AD cases. The bulbous neuritic changes were more prominent in the initial and progressive phases and were reduced in cases with a long clinical course. Conclusion: Our results indicate that there is a prominent difference in the shape and composition of neocortical and archicortical neuritic plaques and, moreover, that bulbous neuritic changes can be observed at a higher rate in AD/DLB and AD/ALB subjects compared to pure AD subjects. This observation probably reflects that these subacute changes are more easily seen in the faster clinical course of AD patients with comorbidities.

Evaluating Thrombin Inhibition in Alzheimer’s Disease (The BEACON Trial): Protocol for a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Cláudia Yang Santos ◽  
Christine Getter ◽  
John Stoukides ◽  
Brian Ott ◽  
Stephen Salloway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Cognitive Performance ◽  
Thrombin Inhibitor ◽  
Placebo Control ◽  
Open Label ◽  
Double Blind ◽  
Thrombin Inhibition ◽  
Approved Drugs

BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multicenter, delayed-start, pilot study evaluating thrombin inhibition in people with biomarker-confirmed MCI probably due to AD or mild AD. 40 - 60 participants will be recruited between 50 - 85 years old. In the initial 9-months of study, either dabigatran or placebo will be orally administered to patients at a dose of 150 mg per day. After 9 months of the placebo-control (Phase I), the placebo arm will cross-over to an active, open-label (Phase II) where all patients will be treated with a 150 mg daily dose of dabigatran orally for an additional 12 months. A 3-month non-treatment follow-up period will assess duration of effects. RESULTS Beginning in July 2019, and concluding in August 2022, this study is expected to publish final results in January 2023. CONCLUSIONS BEACON is a first-in-kind randomized clinical trial targeting thrombin activation in AD therapeutics. This trial will stimulate translational investigations of an FDA-approved drugs in a newly defined therapeutic areas. CLINICALTRIAL Clinicaltrials.gov NCT03752294

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