Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia
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ABSTRACT:
SUBMITTER: Parsons C
PROVIDER: S-EPMC8094886 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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Project description:Background and purposeThis clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer's disease (AD) and other types of dementia.MethodsUsing the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.ResultsThree main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson's disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.ConclusionsThis guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.
| S-EPMC11813556 | biostudies-literature
Project description:Background and objectiveAs dementia progresses, people living with dementia may take high-risk, unnecessary, or ineffective medicines. Cholinesterase inhibitors (ChEIs) may have benefit in some people with dementia; however, up to one third are continued when no longer necessary or safe. Our aim was to co-design a consult patient decision aid (CPtDA) to support shared decision making between healthcare professionals and consumers about continuing or deprescribing ChEIs.MethodsA systematic process was employed to design and test the CPtDA prototype. First, a steering group composed of healthcare professionals and a consumer representative was assembled. Guided by the International Patient Decision Aids Standards, the steering group defined the CPtDA's purpose, scope, and target audience and drafted the prototype for further testing. Interviews with consumers and healthcare professionals were conducted to gain feedback on the content, format, structure, comprehensibility and usability of the CPtDA prototype.ResultsAfter the steering group developed the CPtDA prototype, interviews were conducted with 11 consumers and six healthcare professionals. The content and format of the decision aid were improved iteratively over three rounds after consolidating the feedback at each round. The main changes included rewording the purpose of the decision aid and simplifying its layout and format. Participants reported that the decision aid is comprehensible and may be useful in practice.ConclusionsLimited available resources guide shared decision making about deprescribing. This study resulted in a co-designed and alpha-tested CPtDA for people living with dementia and carers to help them review the ongoing need for their ChEIs. Further research is needed to explore using the CPtDA in practice to support people living with dementia and their carers engage in the shared decision-making process about continuing or deprescribing their ChEIs. Our co-designed CPtDA could help people living with dementia and their carers review their goals of care alongside their healthcare professional. This may prompt conversations about appropriately using ChEIs and increase the uptake of deprescribing.
| S-EPMC11480166 | biostudies-literature
Project description:BACKGROUND:Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). There is an understanding that an increase in L-glutamate contributes to the pathogenesis of cerebral ischemias and AD. Memantine acts as an antagonist of N-methyl-D-aspartate (NMDA) type receptors, which is thought to reduce abnormal activation of glutamate neurotransmission. It binds with a low affinity to the NMDA receptor and so should not prevent learning and the formation of memory. Memantine can improve cognitive function and slow the decline of AD in the general population over time, and is the subject of this review. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population. OBJECTIVES:To determine the effectiveness and safety of memantine for people with DS who develop AD. SEARCH STRATEGY:CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of memantine, as well as experts in the field, to ask about reports of unpublished or ongoing trials. SELECTION CRITERIA:Randomised controlled trials of participants with DS and AD in which treatment with memantine was administered compared with a placebo group. DATA COLLECTION AND ANALYSIS:No study was identified which met the inclusion criteria for this review. MAIN RESULTS:No study was identified which met inclusion criteria for this review, however there is an on-going randomised controlled study being conducted in the UK and data are expected in 2009. AUTHORS' CONCLUSIONS:As there are no included trials, recommendations cannot be made about memantine for AD in DS. Well-designed, adequately powered studies are required.
| S-EPMC7197456 | biostudies-literature
Project description:ObjectivesTo assess the clinical characteristics and course of patients with mild cognitive impairment (MCI) and mild Alzheimer disease (AD) treated with cholinesterase inhibitors (ChEIs) and memantine hydrochloride.DesignCohort study.SettingThe 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative (ADNI).ParticipantsOutpatients with MCI and AD in ADNI.Main outcome measuresThe AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and Functional Activities Questionnaire (FAQ).ResultsA total of 177 (44.0%) of 402 MCI patients and 159 (84.6%) of 188 mild-AD patients were treated with ChEIs and 11.4% of MCI patients and 45.7% of AD patients with memantine at entry. Mild-cognitive-impairment patients who received ChEIs with or without memantine were more impaired, showed greater decline in scores, and progressed to dementia sooner than patients who did not receive ChEIs. Alzheimer-disease patients who received ChEIs and memantine took them longer, were more functionally impaired, and showed greater decline on the MMSE and CDR (but not on the ADAS-cog or FAQ) than those who received ChEIs only.ConclusionsAcademic physicians frequently prescribe ChEIs and memantine earlier than indicated in the US Food and Drug Administration-approved labeling to patients who are relatively more severely impaired or who are rapidly progressing toward cognitive impairment. The use of these medications in ADNI is associated with clinical decline and may affect the interpretation of clinical trial outcomes.Study registrationclinicalTrials.gov Identifier: NCT00106899.
| S-EPMC3259850 | biostudies-literature
Project description: Not available
| S-EPMC1557932 | biostudies-literature
Project description:To compare the risk of pneumonia in older adults receiving donepezil, galantamine, or rivastigmine for dementia.Retrospective cohort study.Nationally representative 5% sample of Medicare databases.Medicare beneficiaries aged 65 and older who newly initiated cholinesterase inhibitor therapy between 2006 and 2009.Pneumonia, defined as the presence of a diagnosis code for pneumonia as the primary diagnosis on an inpatient claim or on an emergency department claim followed by dispensing of appropriate antibiotics. Cox proportional hazards models were used to estimate the risk of pneumonia. Subgroup analyses and sensitivity analyses were conducted using alternative pneumonia definitions and adjustments using high-dimensional propensity scores to test the robustness of the results.The mean age of 35,570 new users of cholinesterase inhibitors (30,174 users of donepezil, 1,176 users of galantamine, 4,220 users of rivastigmine) was 82; 75% were women, and 82% were white. The cumulative incidence of pneumonia was 51.9 per 1,000 person-years. The risk of pneumonia for rivastigmine users was 24% lower than that of donepezil users (hazard ratio (HR)=0.75, 95% confidence interval (CI)=0.60-0.93). Risk in galantamine users (HR=0.87, 95% CI=0.62-1.23) was not significantly different from risk in donepezil users. Results of subgroup and sensitivity analyses were similar to the primary results.The risk of pneumonia was lower in individuals receiving rivastigmine than in those receiving donepezil. Additional studies are needed to confirm the findings of pneumonia risk between the oral and transdermal forms of rivastigmine and in users of galantamine.
| S-EPMC5569896 | biostudies-other
Project description:ImportanceDiscontinuing cholinesterase inhibitors when initiating memantine in patients with dementia may be reasonable to reduce treatment burden, costs, and the risk of adverse drug events.ObjectiveTo assess the association of cholinesterase inhibitor discontinuation on long-term care institutionalization among older adults with dementia who initiate memantine.Design, setting, and participantsThis retrospective propensity score-matched cohort study used Medicare claims data from January 2014 to December 2019. Participants included fee-for-service Medicare beneficiaries with dementia. Data were analyzed from September 2021 to August 2024.ExposuresDiscontinuation vs continuation of cholinesterase inhibitor.Main outcomes and measuresThe primary outcome was 1-year long-term care institutionalization-free days. Secondary outcomes include all-cause death and adverse drug events over 1 year. We performed subgroup analyses based on age, sex, dementia type (Alzheimer disease vs other), frailty, and dementia severity (mild vs moderate or severe) based on claims-based algorithms. The primary outcome was analyzed using nonparametric restricted mean survival time analysis.ResultsAmong 16 292 beneficiaries who initiated memantine, 1820 (11.2%) discontinued cholinesterase inhibitors. In the propensity score-matched cohort of 3612 beneficiaries, the mean (SD) age was 80.7 (6.7) years, 2261 (62.6%) were female, and 1989 (55.0%) had a diagnosis of Alzheimer disease. Over 1 year, long-term care institutionalization occurred in 51 of 1806 beneficiaries (2.8%) who discontinued cholinesterase inhibitors (3.4 per 100 person-years) and 62 of 1806 beneficiaries (3.4%) who continued (4.1 per 100 person-years). There was no statistically significant difference in the 1-year mean institutionalization-free days between discontinuation and continuation groups (360.6 [95% CI, 359.3 to 362.0] days vs 359.1 [95% CI, 357.5 to 360.6] days; mean difference, 1.5 [95% CI,-0.5 to 3.6] days). The mean difference in the long-term care institutionalization-free days did not differ by age category, sex, dementia type, frailty, or dementia stage. Individuals who discontinued had a lower rate of fall-related injury (0.9 vs 2.0 per 100 person-years; hazard ratio [HR], 0.47 [95% CI, 0.25 to 0.88]). There was no difference between the discontinuation and continuation groups in all-cause death (10.4 vs 11.6 per 100 person-years; HR, 0.89 [95% CI, 0.72 to 1.10]).Conclusions and relevanceIn this study, discontinuing cholinesterase inhibitors upon memantine initiation was not associated with an increased risk of long-term care institutionalization but with a lower risk of fall-related injury among older adults with dementia. These findings offer valuable insights for clinicians aiming to reduce treatment burden in this population.
| S-EPMC11577138 | biostudies-literature
Project description:IntroductionWe aimed to assess the impact of cholinesterase inhibitors (ChEIs) and memantine on cognition, major adverse cardiovascular events (MACE) and mortality in dementia with Lewy bodies (DLB).MethodsA total of 1,095 incident DLB patients from the Swedish Registry on cognitive/dementia disorders were included. Using an inverse probability of treatment weighting, the effect of initiating ChEI or memantine within 90 days of DLB diagnosis and nonuse was evaluated on cognitive trajectories and risks of MACE and death.ResultsThe use of ChEIs significantly slowed cognitive decline at follow-ups (Mini-Mental State Examination [MMSE] -0.39 points/y; 95% confidence interval [CI], -0.96 to 0.18) compared to memantine (-2.49 points/y; -4.02 to -0.97) and nonuse (-2.50 points/y; -4.28 to -0.73). Treatment groups did not differ in MACE events. ChEI use was associated with lower risk of death in the first year after DLB diagnosis (adjusted hazard ratio [HR] 0.66, 95% CI 0.46, 0.94).DiscussionOur findings illuminate the potential benefits of ChEI treatment in DLB patients.HighlightsCholinesterase inhibitors slow cognitive decline over a 5-year follow-up period when compared to both memantine treatment and nonuse in patients with dementia with Lewy bodies. Cholinesterase Inhibitors reduce risk of mortality within the initial year, but this effect is not sustained after 1 year in patients with dementia with Lewy bodies.
| S-EPMC11485406 | biostudies-literature
Project description:IntroductionAlzheimer's disease (AD) is the most common neurodegenerative form of dementia. Pharmacological therapies for symptomatic treatment, such as acetylcholinesterase inhibitors (AChEIs) and memantine, have been available in the USA since 2000. Over the past decade, few studies have analyzed real-world anti-dementia treatment patterns in the USA. This study evaluated monotherapy AChEIs and memantine treatment patterns among newly diagnosed AD patients.MethodsA retrospective cohort study was conducted using Medicare data and the Minimum Data Set from 2008 to 2012. Patients aged 65-100 years with newly diagnosed AD (ICD-9 code: 331.0) and monotherapy AChEI or memantine treatment initiated after diagnosis were included. Descriptive treatment pattern analyses, including discontinuation and switch, were undertaken. Kaplan-Meier curves were developed to examine the treatment duration.ResultsA total of 9812 newly diagnosed AD patients were identified, with 56.7% (n = 5567) first receiving anti-dementia treatment after the initial AD diagnosis. Among patients initiating monotherapy AChEIs or memantine after AD diagnosis (N = 5200), 51.6% continued index treatment during the entire follow-up period (mean follow-up: 659.7 days) and 21.7% discontinued treatment. Of those who initiated monotherapy treatment with an AChEI, 11.1% received adjunct therapy with memantine. Among patients with ≥1 year of continuous treatment (mean follow-up: 834 days), 75.6% remained on the index drug, 10.2% discontinued during the remaining follow-up period, and 9.5% of the AD patients initiating AChEIs received adjunct memantine therapy during the remaining follow-up period.ConclusionIn the USA Medicare population, about 50% of the patients who initiated treatment with AChEI or memantine after diagnosis continued the index treatment, and more than 20% discontinued and were untreated afterwards over the observation period. AD patients initiating AChEIs or memantine were more likely to remain on their treatment if they were persistently treated for the first year.
| S-EPMC5447560 | biostudies-literature
Project description: Not available
| S-EPMC8985413 | biostudies-literature