Role of cholinesterase inhibitors in dementia care needs rethinking.
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ABSTRACT:
SUBMITTER: Pelosi AJ
PROVIDER: S-EPMC1557932 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: Not available
| S-EPMC8985413 | biostudies-literature
Project description:IntroductionWe investigated whether cholinesterase inhibitors (ChEIs) benefit cognitive outcomes in mild cognitive impairment due to Alzheimer disease (MCI-AD) and in mild AD dementia (ADdem).MethodsData from 2242 individuals, clinically diagnosed with MCI-AD [Clinical Dementia Rating (CDR), 0 or 0.5] or with mild ADdem (CDR, 0.5 or 1), were available from the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS). General linear mixed models were used to examine the annual change in the CDR Sum of Boxes (CDR-SB) and in neuropsychological performance. We compared slopes before and after ChEI initiation among ChEI users, and also compared the change in scores of ChEI users versus nonusers.ResultsThirty-four percent of 944 MCI-AD and 72% of 1298 ADdem participants were ChEI users. Cognitive decline was greater after ChEI initiation in MCI-AD and ADdem groups (eg, MCI-AD, CDR-SB: 0.03 points/y before initiation; 0.61 points/y after initiation, P<0.0001). Both MCI-AD and ADdem groups had faster decline after ChEI initiation than nonusers (eg, MCI-AD, CDR-SB: 0.61 points/y, ChEI users; 0.24 points/y, nonusers, P<0.0001).DiscussionThis study suggests that ChEI use may not improve the cognitive course in MCI-AD and mild ADdem.
| S-EPMC6542289 | biostudies-literature
Project description: Not available
| S-EPMC8094886 | biostudies-literature
Project description: Not available
| S-EPMC7492068 | biostudies-literature
Project description: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.
| S-EPMC7253642 | biostudies-literature
Project description:Non-communicable chronic diseases (NCCDs) are the main cause of morbidity and mortality globally. Demographic aging has resulted in older populations with more complex healthcare needs. This necessitates a multilevel rethinking of healthcare policies, health education and community support systems with digitalization of technologies playing a central role. The European Innovation Partnership on Active and Healthy Aging (A3) working group focuses on well-being for older adults, with an emphasis on quality of life and healthy aging. A subgroup of A3, including multidisciplinary stakeholders in health care across Europe, focuses on the palliative care (PC) model as a paradigm to be modified to meet the needs of older persons with NCCDs. This development paper delineates the key parameters we identified as critical in creating a public health model of PC directed to the needs of persons with NCCDs. This paradigm shift should affect horizontal components of public health models. Furthermore, our model includes vertical components often neglected, such as nutrition, resilience, well-being and leisure activities. The main enablers identified are information and communication technologies, education and training programs, communities of compassion, twinning activities, promoting research and increasing awareness amongst policymakers. We also identified key 'bottlenecks': inequity of access, insufficient research, inadequate development of advance care planning and a lack of co-creation of relevant technologies and shared decision-making. Rethinking PC within a public health context must focus on developing policies, training and technologies to enhance person-centered quality life for those with NCCD, while ensuring that they and those important to them experience death with dignity.
| S-EPMC7503185 | biostudies-literature
Project description:Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the compounds demonstrated insignificant toxicity. All the compounds showed rather moderate inhibitory effect against AChE; benzyl (2S)-2-[(2-chlorophenyl)carbamoyl]pyrrolidine-1-carboxylate (IC50 = 46.35 μM) was the most potent agent. On the other hand, benzyl (2S)-2-[(4-bromophenyl)-] and benzyl (2S)-2-[(2-bromophenyl)carbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity (IC50 = 28.21 and 27.38 μM, respectively) comparable with that of rivastigmine. The ortho-brominated compound as well as benzyl (2S)-2-[(2-hydroxyphenyl)carbamoyl]pyrrolidine-1-carboxylate demonstrated greater selectivity to BChE. The in silico characterization of the structure-inhibitory potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties was provided using comparative molecular surface analysis (CoMSA) and principal component analysis (PCA). Moreover, the systematic space inspection with splitting data into the training/test subset was performed to monitor the statistical estimators performance in the effort to map the probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile revealed potentially relevant structural and physicochemical features that might be essential for mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the reaction site by the substituent in the 3'-/4'-position of the phenyl ring. In addition, the investigation was completed by a molecular docking study of recombinant human AChE.
| S-EPMC6150311 | biostudies-literature
Project description:OBJECTIVES:This study explored the process of care for persons living with dementia (PLWDs) in various care settings across a tertiary care system and considers challenges and opportunities for change. DESIGN:Aimed at quality improvement, qualitative interviews were conducted with key stakeholders in dementia care across geriatric outpatient clinics, medical and psychiatric emergency departments, and the main hospital in 2016. SETTING AND PARTICIPANTS:Forty-nine interactive interviews were conducted with a purposive and snowball sampling of health care professionals (physicians, nurses, social workers, administrators) and families in a large, academic health care system. MEASURES:Qualitative interview guides were developed by the study team to assess the process of care for PLWDs and strengths and challenges to delivering that care. RESULTS:Key themes emerging from the interviews in each care setting are presented. The outpatient setting offers expertise, a multidisciplinary clinic, and research opportunities, but needs to respond to long waitlists, space limitations, and lack of consensus about who owns dementia care. The emergency department offers a low nurse/patient ratio and expertise in acute medical problems, but experiences competing demands and staff turnover; additionally, dementia does not appear on medical records, which can impede care. The hospital offers consultative services and resources, yet the physical space is confined and chaotic; sitters and antipsychotics can be overused, and placement outside of the hospital for PLWDs can be a challenge. CONCLUSIONS AND IMPLICATIONS:Five key recommendations are provided to help health systems proactively prepare for the coming boom of PLWD and their caregivers, including outpatient education, a dementia care management program to link services, Internet-based training for providers, and repurposing sitters as Elder Life specialists.
| S-EPMC6768732 | biostudies-literature
Project description:Background/objectivesPeople with dementia (PwD) frequently use emergency care services. To mitigate the disproportionately high rate of emergency care use by PwD, an understanding of contributing factors driving reliance on emergency care services and identification of feasible alternatives are needed. This study aimed to identify clinician, caregiver, and service providers' views and experiences of unmet needs leading to emergency care use among community-dwelling PwD and alternative ways of addressing these needs.DesignQualitative, employing semistructured interviews with clinicians, informal caregivers, and aging service providers.SettingWisconsin, United States.ParticipantsInformal caregivers of PwD (n = 4), emergency medicine physicians (n = 4), primary care physicians (n = 5), geriatric healthcare providers (n = 5), aging service providers (n = 6), and community paramedics (n = 3).MeasurementsDemographic characteristics of participants and data from semistructured interviews.FindingsFour major themes were identified from interviews: (1) system fragmentation influences emergency care use by PwD, (2) informational, decision-making, and social support needs influence emergency care use by PwD, (3) emergency departments (EDs) are not designed to optimally address PwD and caregiver needs, and (4) options to prevent and address emergency care needs of PwD.ConclusionParticipants identified numerous system and individual-level unmet needs and offered many recommendations to prevent or improve ED use by PwD. These novel findings, aggregating the perspectives of multiple dementia-care stakeholder groups, serve as the first step to developing interventions that prevent the need for emergency care or deliver tailored emergency care services to this vulnerable population through new approaches. J Am Geriatr Soc 67:711-718, 2019.
| S-EPMC6458085 | biostudies-literature