Cholinesterase Inhibitors In Patients Research Articles

Efficacy of Acetylcholinesterase Inhibitors in the Logopenic Variant of Primary Progressive Aphasia

Introduction: For over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer’s disease (AD). Several meta-analyses have supported their effectiveness in various neurocognitive, functional, and behavioral aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA), also named language variant AD, are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their evolution on the MMSE, and other functional and behavioral parameters, to that of treated amnestic AD patients. Methods: A retrospective chart review was performed in 45 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar in terms of age, level of education, and onset of symptoms. Drug history and MMSE scores, as well as functional (activities of daily living [ADLs] and instrumental activities of daily living [IADLs]), neurocognitive and neuropsychiatric symptoms were collected on several time points before and after the introduction of ChEIs. Data were analyzed using ANOVA and a generalized linear mixed model. Results: Patients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs up to 12–24 months after the introduction of ChEIs. There was a significant impact on ADLs but not IADLs and neuropsychiatric symptoms remained stable over time. Conclusion: This study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients, hence reassuring patients and their physicians.

Postoperative Gastrointestinal Dysfunction After Neuromuscular Blockade Reversal With Sugammadex Versus Cholinesterase Inhibitors in Patients Undergoing Gastrointestinal Surgery: A Systematic Review and Meta-Analysis.

Postoperative gastrointestinal dysfunction (POGD) commonly occurs following gastrointestinal (GI) surgery and is associated with specific anesthetic agents. Cholinesterase inhibitors employed for reversing neuromuscular blockade have been implicated in development of POGD. Sugammadex, a novel reversal agent, is linked with reduced POGD. However, there is a lack of comprehensive comparative review between these agents regarding their impact on POGD following GI surgery. This study aims to systematically review the effects of sugammadex on POGD compared to cholinesterase inhibitors following GI surgery. MEDLINE, EMBASE, and CENTRAL were searched as of July 2022 to identify articles comparing sugammadex with cholinesterase inhibitors in patients undergoing gastrointestinal surgery, specifically in relation to POGD. Secondary endpoints included length of hospital stay, readmission rates, pulmonary complications, and postoperative morbidity. From 198 citations, 2 randomized controlled trials (RCTs) and 3 retrospective cohorts with 717 patients receiving sugammadex and 812 patients receiving cholinesterase inhibitors were included. Significantly lower rates of prolonged postoperative ileus (OR .44, 95% CI .25-.77, P < .05, I2 = 56%, low certainty evidence) was observed with sugammadex. No significant difference in any other outcome was observed. Narrative review of readmission data demonstrated no significant difference. The use of sugammadex following gastrointestinal surgery is associated with significantly lower rates of prolonged postoperative ileus compared to cholinesterase inhibitors. However, these do not translate into a significant reduction in length of stay, morbidity, or postoperative nausea and vomiting. Results are limited by the numer of studies included and missing data, more robust RCTs are needed before recommendations can be made.

Study on the effectiveness of acetylcholinesterase inhibitors in the treatment of primary progressive logopenic aphasia

AbstractBackgroundFor over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer’s disease (AD). Several meta‐analyses have supported their effectiveness in various neurocognitive aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA) are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their longitudinal MMSEs to that of treated amnestic AD patients.MethodA retrospective chart review was performed on 48 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar with respect to age, level of education, and onset of symptoms. Drug history and MMSE scores were collected on several time points before and after the introduction of ChEIs.ResultsPatients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs (both WORLD and 100‐7) up to twelve months after the introduction of ChEIs (Figure 1 and 2).ConclusionThis study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients.

Electrocardiographic Effects of Cholinesterase Inhibitors in Patients with Alzheimer’s Disease

Electrocardiographic Effects of Cholinesterase Inhibitors in Patients with Alzheimer’s Disease

Electrocardiographic Effects of Cholinesterase Inhibitors in Patients with Alzheimer’s Disease

Electrocardiographic Effects of Cholinesterase Inhibitors in Patients with Alzheimer’s Disease

Cholinesterase Inhibitor Use in Patients With Dementia Admitted to a Palliative Care Unit.

Current guidelines suggest that patients with severe dementia on cholinesterase inhibitors (CHEIs) should discontinue their CHEIs by taper. This study aims to define the prevalence of patients admitted to a palliative care unit (PCU) with dementia on a CHEI and to determine whether these patients were tapered off their CHEIs according to current deprescribing guidelines. This is a descriptive retrospective chart review that examined patients admitted to a PCU with dementia on a CHEI from January 2015 to June 2019. Individuals admitted to the PCU with a primary or comorbid diagnosis of dementia were identified. Their corresponding CHEI dose, frequency and discontinuation pattern were identified. Data were analyzed using descriptive statistics. A total of 36 patients were admitted to the PCU with dementia on a CHEI (prevalence of 2.3%). The median length of stay was 21 days. For 31 of these patients, their CHEI was discontinued, only 9 of which had a taper. Of the 24 patients who discontinued their CHEI suddenly, 10 patients had an order to discontinue their CHEI in the last 2 days before their date of death. This study suggests that although patients admitted to a PCU with dementia have their CHEI discontinued, the discontinuation was done without a taper. In many cases the CHEIs were continued through the active stage of dying. Future work should explore reasons why PCU physicians are mostly late to taper CHEIs for patients admitted with dementia.

Potential synergistic effect between Fortasyn Connect and cholinesterase inhibitors in patients with early stages (very mild and mild) of dementia due to Alzheimer disease in common medical practice: An observational, non‐interventional study

AbstractBackgroundDetails implementation of an innovative care program or practice: Fortasyn connect medical food, approved for early stages of Alzheimer dementia, can have a synergistic effect with cholinesterase inhibitors drugs.ObjectivesTo analyse the possible synergistic effect between Fortasyn Connect medical food and Cholinesterase Inhibitors drugs in Alzheimer disease patients in a common medical practice.Patients and Methods60 patients at early stages of dementia due to Alzheimer disease were followed. CDR (Clinical Dementia Rating) scale was administered at the beginning and at the end of the follow‐up period. The rate of change of CDR‐SB (sum of Blocks) was chosen as a efficacy criteria. Informed Consent was aquired. An approval of the Ethical Committee of the protocol was obtained. SSPS (v20) was used as a Statistical Software.ResultsThe combination therapy with Fortasyn Connect and Cholinesterase inhibitors was well tolerated. There were no significative advers effect. The patients were distribute at the final visit in 4 groups: Those who had taken both Fortasyn Connect and Cholinesterase inhibitors (Group 1), those who had taken Fortasyn Connect and no Cholinesterase inhibitors (Group 2), those who had taken Cholinesterase inhibitors and non Fortasyn Connect (Group 3), those who had not taken neither Fortasyn Connect nor Cholinesterase inhibitors (Group 4). There was a statistical difference between the Group 1 with the Group 3 and Group 4, indicating a potential synergistic effect between both therapies.ConclusionsThe combination therapy with Fortasyn Connect medical food and Cholinesterase inhibitors was well tolerated. It seem to be a potential synergistic efect between Fortasyn Connect medical food and Cholinesterase inhibitors Drugs. An statistical difference between the Group 1 (Fortasyn Connect medical food and Cholinesterase inhibitors therapy) with the Group 3 (Cholinesterase Inhibitor alone) and Group 4 (Fortasyn Connect medical food and Cholinesterase inhibitors therapy), indicating a potential synergistic effect between both therapies. Due to the limitations of this preliminary study (non‐blinded, non randomized, small sample of patients, non placebo control), more studies are needed.

Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer's Dementia Are Frequently Below the Recommended Levels.

BackgroundAcetylcholinesterase inhibitors (AChE-I) are recommended for the treatment of cognitive symptoms but also of behavioral and psychological symptoms in dementia. They are widely used not only in Alzheimer's disease, but also in other forms of dementia. Efficacy of treatment might depend on serum concentration of the respective AChE-I.ObjectiveIn patients with mild to moderate Alzheimer's dementia, we measured serum concentrations of hepatically metabolized donepezil and renally excreted rivastigmine and investigated possible modifiers. Additionally, we looked at correlations between serum concentrations and efficacy for both drugs.MethodsSerum concentrations of donepezil and rivastigmine were measured by liquid chromatography – tandem mass spectrometry (LC-MS/MS). Real-time quantitative polymerase chain reaction (PCR). Allele specific PCR were performed to determine CYP2D6 genotype and gene dose. Clinical efficacy was assessed by changes of the subtest wordlist delayed recall of the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB).ResultsSixty-seven patients treated with a stable dosage of donepezil 10 mg (n=41) or rivastigmine 9.5 mg (n=26) were included. Mean serum concentration of donepezil and rivastigmine were 41.2 and 6.5 ng/ml, respectively. Serum concentrations were below the recommended range in 73% of the subjects in the donepezil group and in 65% of the participants in the rivastigmine group. When applying a dose-related reference, ranges 63% of patients in the donepezil group and 32% in the rivastigmine group had concentrations below the expected range. Gene dose, sex, and duration of treatment significantly predicted donepezil serum concentration (p=0.046, p=0.001, p=0.030 respectively). Only for rivastigmine did the serum concentration significantly contribute to the regression model predicting changes on the subtest word list delayed recall (β=0.472; p=0.019).ConclusionsSerum concentrations of about two thirds of the patients were below the recommended range. When not looking at absolute values but at the dose-related reference ranges, these numbers improved but still 32%, respectively 63% of patients had low serum concentrations. High serum concentrations of rivastigmine predicted clinical response to cognition. Therapeutic drug monitoring might help to identify the cause of poor clinical response to cognition and behavioral and psychological symptoms in patients with AChE-I treatment.

Cholinesterase inhibitors in patients with diabetes mellitus and dementia: an open-cohort study of ~23 000 patients from the Swedish Dementia Registry

ObjectiveCholinesterase inhibitors (ChEIs) and memantine are the only approved pharmacological treatments for Alzheimer’s disease (AD). Recent literature suggests reductions in cardiovascular burden and risk of stroke in ChEI users. However,...

P.776 Effects of the CYP2D6 polymorphism and concurrent medications on plasma concentrations of cholinesterase inhibitors in patients with dementia

The avionics system organization is a systemic structured organization. The application task layer, system function layer, and physical equipment layer have independent organization, operation and management modes, supporting system tasks, functions and equipment operation and management, and providing overall system organization and management capabilities. By building an avionics system application task layer, system function layer, and physical equipment layer integrated organization and management, the avionics system integration constructs system application tasks, function processing, and physical resources integration operation process to achieve system application tasks, function processing, and physics resource integration optimization goals.Chapter 7 can be divided into five sections. Section 1 introduces the system applications, capabilities, and equipment components. Section 2 describes the flight application mission, system function capabilities, and equipment physical resources integration mode. For the system integration organization, Section 3 describes the system task composition and organization process oriented to the target requirements of flight applications, the system function structure and organization process oriented to application task operation requirements, and the equipment resource composition and organization process oriented to system function processing requirements. Section 4 describes the system function mode of system applications, functions, and equipment. Finally, Section 5 describes the comprehensive technical organization architecture of system application tasks, system functions, and equipment resources.

Detection of severity in Alzheimer's disease (AD) using computational modeling.

The prevalent cause of dementia - Alzheimer's disease (AD) is characterized by an early cholinergic deficit that is in part responsible for the cognitive deficits (especially memory and attention defects). Prolonged AD leads to moderate-to-severe AD, which is one of the leading causes of death. Placebo-controlled, randomized clinical trials have shown significant effects of Acetyl cholin esterase inhibitors (ChEIs) on function, cognition, activities of daily living (ADL) and behavioral symptoms in patients. Studies have shown comparable effects for ChEIs in patients with moderate-to-severe or mild AD. Setting a fixed measurement (e.g. a Mini-Mental State Examination score, as a 'when to stop treatment limit) for the disease is not clinically rational. Detection of changed regional cerebral blood flow in mild cognitive impairment and early AD by perfusion-weighted magnetic resonance imaging has been a challenge. The utility of perfusion-weighted magnetic resonance imaging (PW-MRI) for detecting changes in regional cerebral blood flow (rCBF) in patients with mild cognitive impairment (MCI) and early AD was evaluated. We describe a computer aided prediction model to determine the severity of AD using known data in literature. We designed an automated system for the determination of AD severity. It is used to predict the clinical cases and conditions with disagreements from specialist. The model described is useful in clinical practice to validate diagnosis.

Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer's Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients.

Background:We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer’s disease.Methods:A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework.Results:Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65).Conclusion:While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer’s disease.

Early Therapeutic Intervention by Cholinesterase Inhibitors in Patients with Alzheimer’s Disease

Early Therapeutic Intervention by Cholinesterase Inhibitors in Patients with Alzheimer’s Disease

Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias.

(Reprinted with permission from American Psychiatric Association, http://psychiatryonline.org/guidelines).

IDALOPIRDINE, A 5-HT6 ANTAGONIST IN PHASE III DEVELOPMENT AS ADJUNCTIVE THERAPY TO CHOLINESTERASE INHIBITORS IN PATIENTS WITH MILD-TO-MODERATE ALZHEIMER’S DISEASE: BASELINE DATA FROM THE ONGOING STARSHINE STUDY

IDALOPIRDINE, A 5-HT6 ANTAGONIST IN PHASE III DEVELOPMENT AS ADJUNCTIVE THERAPY TO CHOLINESTERASE INHIBITORS IN PATIENTS WITH MILD-TO-MODERATE ALZHEIMER’S DISEASE: BASELINE DATA FROM THE ONGOING STARSHINE STUDY

A 5-HT6 Antagonist as Adjunctive Therapy to Cholinesterase Inhibitors in Patients with Mild-to-Moderate Alzheimer’s Disease: Idalopirdine in Phase III (PL02.006)

A 5-HT6 Antagonist as Adjunctive Therapy to Cholinesterase Inhibitors in Patients with Mild-to-Moderate Alzheimer’s Disease: Idalopirdine in Phase III (PL02.006)

Poster Number: NR 16 - A 5-HT6 Antagonist as Adjunctive Therapy to Cholinesterase Inhibitors in Patients with Mild-to-Moderate Alzheimer's Disease: Idalopirdine in Phase III

Poster Number: NR 16 - A 5-HT6 Antagonist as Adjunctive Therapy to Cholinesterase Inhibitors in Patients with Mild-to-Moderate Alzheimer's Disease: Idalopirdine in Phase III

Idalopirdine, a 5-HT6 antagonist in Phase III development as adjunctive therapy to cholinesterase inhibitors in patients with mild-to-moderate Alzheimer’s disease: the observed case analyses of the Phase II study

Idalopirdine, a 5-HT6 antagonist in Phase III development as adjunctive therapy to cholinesterase inhibitors in patients with mild-to-moderate Alzheimer’s disease: the observed case analyses of the Phase II study

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer's disease: a Bayesian network meta-analysis.

BackgroundComparative evidence for efficacy and safety of second‐generation cholinesterase inhibitors (ChEIs) is still sparse.ObjectivesThe purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild‐to‐moderate Alzheimer's disease (AD).MethodsWe conducted a systematic review for published articles and included randomised, double‐blind, placebo‐controlled trials and head‐to‐head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS‐Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview‐Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta‐analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions.ResultsAmong the 21 trials included, network meta‐analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS‐Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety.ConclusionsOur analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild‐to‐moderate AD.

Treatment of Mild Cognitive Impairment.

It is increasingly evident that early identification of cognitive impairment in older adults presents opportunities for interventions that aim to mitigate the impact of cognitive symptoms on daily function and that attempt to delay (or ultimately prevent) progression from mild cognitive impairment (MCI) to dementia. To date, no intervention has proven protective in ultimately preventing conversion to dementia. However, several lifestyle, dietary, and pharmacologic interventions have suggested symptomatic benefit for those having MCI. A number of diet and lifestyle recommendations have been associated with decreased risk of dementia both in cognitively intact older adults and in those having mild cognitive impairment. Thus, these recommendations may be appropriate for both people presenting with subjective cognitive concerns and for those having objective evidence of memory problems. It remains less certain whether adopting these lifestyle habits in later life confers the benefits seen in epidemiological cohorts (where people have likely practiced them for many years). Discussion of starting on a cholinesterase inhibitor is appropriate for those having MCI, particularly those in whom the MCI is thought to have a vascular etiology or to represent the prodromal stage of a neurodegenerative disease. Recent meta-analyses exploring the use of cholinesterase inhibitors in patients having MCI have concluded that there is no evidence to support this practice. Although meta-analytic techniques seemingly strengthen the confidence in a recommendation via the incorporation of a large number of subjects analyzed, the technique is not capable of overcoming any inherent weaknesses of the individual studies included in the analysis. It is arguable whether studies in MCI may have employed endpoints poorly adapted to investigating effect of cholinesterase inhibitors. Most studies have used cognitive screening examinations, all of which stretch their detection ability to identify subjects with MCI, let alone discriminate subtle differences between them. Some have used conversion from MCI to dementia as an endpoint, which may not be the best measure for a symptomatic treatment. Further, once conversion to dementia has occurred, a cholinesterase inhibitor would be started in most (if not all) clinical settings, a reality not well reflected in most study designs. Additionally, several large studies have not permitted subject stratification by APOE carrier status, another important defect in assessing outcome. In clinical practice, our center typically does recommend cholinesterase inhibitors for patients having MCI. Despite the modest effect size, many patients do wish to start on treatment. It appears that this is a generally accepted practice and experience, as most clinical trials for prodromal Alzheimer's disease specify that participants should be taking a cholinesterase inhibitor.