Use Of Cholinesterase Inhibitors Research Articles

Early-onset dementia and risk of hip fracture and major osteoporotic fractures.

There is limited knowledge about early-onset dementia (EOD) on fracture risk. Individuals ages 50 to 64 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (2012 to 2019). The association between EOD and fractures and the association between cholinesterase inhibitors for EOD and fractures were evaluated using logistic regression analyses. We identified 13,614 EOD patients and 9,144,560 cognitively healthy individuals. The analysis revealed that EOD was associated with an increased risk of hip fractures (adjusted odds ratio, 95% confidence interval: 8.79, 7.37-10.48), vertebral fractures (1.73, 1.48-2.01), and major osteoporotic fractures (2.05, 1.83-2.30) over 3 years. The use of cholinesterase inhibitors was significantly associated with a reduction in hip fractures among EOD patients (0.28, 0.11-0.69). EOD patients have a higher risk of osteoporotic fractures than cognitively healthy individuals. The use of cholinesterase inhibitors may reduce the risk of hip fracture among EOD patients. It is unknown whether early-onset dementia (EOD) increases the risk of fractures. We identified 13,614 individuals with EOD using a nationwide administrative database. Patients with EOD have a higher risk of hip, vertebral, and major osteoporotic fractures. The use of cholinesterase inhibitors may reduce hip fracture among patients with EOD.

Differences in the treatment needs of patients with dementia with Lewy bodies and their caregivers and differences in their physicians’ awareness of those treatment needs according to the clinical department visited by the patients: a subanalysis of an observational survey study

BackgroundWe investigated whether the treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers, along with their attending physicians’ perception of those treatment needs, differ according to the clinical department visited by the patients.MethodsThis was a subanalysis of a multicenter, cross-sectional, observational survey study. Data from the main study were classified according to the clinical department visited by the patient: psychiatric group (P-group), geriatric internal medicine group (G-group), and neurology group (N-group). The treatment needs of patients and caregivers were defined as “the symptom that causes them the most distress”, and the frequency of each answer was tabulated.ResultsThis subanalysis included 134, 65, and 49 patient–caregiver pairs in the P-, G-, and N-groups, respectively. Statistically significant differences in patient background characteristics such as patient age; initial symptom domains; use of cholinesterase inhibitors, levodopa, antipsychotics, and Yokukansan; and total scores of the Mini-Mental State Examination, Neuropsychiatric Inventory-12, and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Parts II and III were shown among the three subgroups. While there were no differences in patients’ treatment needs among the subgroups, residual analysis showed that in the N-group, parkinsonism was more of a problem than other symptom domains (p = 0.001). There were significant differences in caregivers’ treatment needs among the three subgroups (p < 0.001). The patient–physician concordance rates for the symptom domains that caused patients the most distress were: P-group, 42.9% (kappa coefficient [κ] = 0.264); G-group, 33.3% (κ = 0.135), and N-group, 67.6% (κ = 0.484). The caregiver–physician concordance rates for the symptom domains that caused the caregivers the most distress were: P-group, 54.8% (κ = 0.351), G-group, 50.0% (κ = 0.244), and N-group, 47.4% (κ = 0.170).ConclusionThis subanalysis revealed differences in the treatment needs of patients with DLB and their caregivers according to the clinical department they attended. There might be a lack of awareness of those treatment needs by the attending physicians, regardless of their specialty.Trial registrationUMIN Clinical Trials Registry UMIN000041844.

Cumulative Anticholinergic Burden and its Predictors among Older Adults with Alzheimer's Disease Initiating Cholinesterase Inhibitors.

Cumulative anticholinergic burden refers to the cumulative effect of multiple medications with anticholinergic properties. However, concomitant use of cholinesterase inhibitors (ChEIs) and anticholinergic burden can nullify the benefit of the treatment and worsen Alzheimer's disease (AD). A literature gap exists regarding the extent of the cumulative anticholinergic burden and associated risk factors in AD. Therefore, this study evaluated the prevalence and predictors of cumulative anticholinergic burden among patients with AD initiating ChEIs. A retrospective longitudinal cohort study was conducted using the Medicare claims data involving parts A, B, and D from 2013 to 2017. The study sample included older adults (65 years and older) diagnosed with AD and initiating ChEIs (donepezil, rivastigmine, or galantamine). The cumulative anticholinergic burden was calculated based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using the defined daily dose over the 1 year follow-up period after ChEI initiation. Incremental anticholinergic burden levels were dichotomized into moderate-high (sum of standardized daily anticholinergic exposure over a year (TSDD) score ≥ 90) versus low-no (score 0-89). The Andersen Behavioral Model was used as the conceptual framework for selecting the predictors under the predisposing, enabling, and need categories. A multivariable logistic regression model was used to evaluate the predictors of high-moderate versus low-no cumulative anticholinergic burden. A multinomial logistic regression model was also used to determine the factors associated with patients having moderate and high burdens compared to low/no burdens. The study included 222,064 older adults with AD with incident ChEI use (mean age 82.24 ± 7.29, 68.9% females, 83.6% White). Overall, 80.48% had some anticholinergic burdenduring the follow-up, with 36.26% patients with moderate (TSDD scores 90-499), followed by 24.76% high (TSDD score > 500), and 19.46% with low (TSDD score 1-89) burden categories. Predisposing factors such as age; African American, Asian, or Hispanic race; and need factors included comorbidities such as dyslipidemia, syncope, delirium, fracture, pneumonia, epilepsy, and claims-based frailty index were less likely to be associated with the moderate-high anticholinergic burden. The factors that increased the odds of moderate-high burden were predisposing factors such as female sex; enabling factors such as dual eligibility and diagnosis year; and need factors such as baseline burden, behavioral and psychological symptoms of dementia, depression, insomnia, urinary incontinence, irritable bowel syndrome, anxiety, muscle spasm, gastroesophageal reflux disease, heart failure, and dysrhythmia.Most of these findings remained consistent with multinomial logistic regression. CONCLUSION: Four out of five older adults with AD had some level of anticholinergic burden, with over 60% having moderate-high anticholinergic burden. Several predisposing, enabling, and need factors were associated with the cumulative anticholinergic burden. The study findings suggest a critical need to minimize the cumulative anticholinergic burden to improve AD care.

The Availability and Use of Anti‐Dementia Drugs: An International Survey

AbstractBackgroundThere is currently no cure for dementia and few medications to help with the symptoms of dementia. However, there are acetylcholinesterase inhibitors, such as Donepezil, Rivastigmine and Galantamine, which are available to people with dementia but there is potential for inequality in their availability globally. A potential reason for this is that there is no anti dementia medication included in the World Health Organisation’s Essential Medicine List which potentially creates inequalities of access to evidence based care.MethodIn collaboration with Alzheimer’s Disease International, a global electronic survey was sent to explore the international use of cholinesterase inhibitors. Here we focus on donepezil as the most commonly prescribed first line anti‐dementia medicationResultIn total we received 73 responses from 39 different countries with all continents represented. Respondents included psychiatrists (n = 21), neurologists (n = 18), physicians (n = 8), geriatricians (n = 7), nurses (n = 4), general practitioners (n = 2), a psychologist (n = 1) and a pharmacist (n = 1). Respondents from all levels of income were included. The majority of participants (n = 66, 90.4%) did prescribe anti‐dementia medications and for the majority of these respondents (n = 50, 68.5%), Donepezil was the first line anti‐dementia medication. Nearly half of all participants (n = 31, 42.5%) reported that they would prescribe anti‐psychotic medication for dementia if they could not access anti‐dementia medication. The efficacy of anti‐dementia drugs was mainly determined by family or carer reports (n = 64, 87.7%) followed by cognitive assessment (n = 54, 74%) and then the patient’s subjective account (n = 50, 68.5%). Participants when asked about their criteria for stopping anti‐dementia medications mainly reported that it was side/adverse effects and how globally/holistically effective the medication was rather than cognitive assessment alone.ConclusionThere are concerns that without access to commonly prescribed anti‐dementia drugs, this may introduce harms to people with dementia as they could be prescribed antipsychotics instead. Emphasis should be given to find ways for all people living with dementia, regardless of geographic or socioeconomic status, to access effective and safe anti‐dementia drugs such as donepezil.

Characterize demographics, comorbidities and co‐medications in newly diagnosed United States (US) Alzheimer’s Disease patients using Medicare claims

AbstractBackgroundAccess to Medicare claims provides a unique opportunity to broadly characterize diseases affecting US adults 65+ years of age. This can provide insights into real world populations and a basis of comparison to those in clinical trial populations. To this end, this study characterizes demographics, comorbidities and co‐medications in patients newly diagnosed with Alzheimer’s Disease (AD).MethodsThis study utilized Medicare Part A and B claims (Fee‐For‐Service and Medicare Advantage) limited to patients with at least one 2019 medical encounter. The study’s source population was limited to those 65+ years of age with Medicare Part D coverage and 1‐year pre‐encounter continuous enrollment. From this source population, three newly diagnosed AD cohorts were compiled; cohort 1 utilized the 1‐year Bynum‐Standard Alzheimer’s disease and related dementia (ADRD) claims algorithm, cohort 2 adapted the ADRD algorithm to include only specific AD diagnoses, and cohort 3 was selected based on new use of cholinesterase inhibitors (irrespective of ADRD diagnosis). Demographics, comorbidities, and co‐medications present in the 1‐year pre‐cohort qualification are described.ResultsFrom 53,890,958 patients with at least one 2019 medical encounter, 33,315,038 qualified for the source population. Of these patients, 861,727 (2.6%) were newly diagnosed with ADRD (cohort 1), 373,798 patients (1.1%) were newly diagnosed with AD (cohort 2), and 395,319 patients (1.2%) were new users of cholinesterase inhibitors (cohort 3). The cohorts were not mutually exclusive. Overall, the three cohorts were similar in terms of demographics (table 1) with 75.1‐85.3% of patients aged 75+ and 61.5‐66.4% female. Common comorbidities (table 2) across the 3 cohorts include cardiovascular (CV) comorbidities such as myocardial infarction (34.1‐41.9%) and heart failure (39.8‐51.4%), diabetes (38.5‐41.6%), arthritis (44.0‐46.6%), stroke (28.9‐34.4%) and anxiety/depression (48.6‐54.5%). Co‐medications received (table 3) such as anti‐hypertensives, lipid modifying drugs, anti‐diabetics, systemic corticosteroids, and anti‐depressants reflect these conditions.ConclusionExtensive understanding of a drug’s real‐world target population can inform generalizability of clinical trial results and highlight unaddressed risk. This study stresses the importance of studying new AD drugs in populations with a history of CV risk, diabetes and stroke as well as those that may be immunocompromised due to treatments with systemic corticosteroids.

A - 63 Neuropsychiatric and Cognitive Correlates of Pareidolias in Dementia with Lewy Bodies.

Pareidolias represent visual illusions of meaningful objects in ambiguous stimuli. Prior research has demonstrated phenomenological similarities between pareidolias and visual hallucinations (VH) and the potential clinical utility of pareidolias in discriminating dementia with Lewy bodies (DLB) from Alzheimer's dementia (ad). Though pareidolias have been linked with VH severity in DLB, the relationships between pareidolias and other neuropsychiatric symptoms have not been explored in large DLB samples. Individuals meeting 2017 McKeith criteria for probable DLB (n = 114) were enrolled in a multi-site systematic longitudinal study of the US DLB Consortium. Study assessments included an informant-rated psychiatric inventory (NPI), Montreal Cognitive Assessment (MoCA), and Noise Pareidolia Task (NPT). Ninety-five participants completed all clinical assessments. To examine baseline relationships between pareidolias responses (NPT) and the presence of 12 neuropsychiatric symptom dimensions (NPI), we used Poisson regression models with robust standard error estimates adjusted for age, education, disease duration, cognition (MoCA), and cholinesterase inhibitor use. Contrary to expectation, the presence of VH was not associated with pareidolias in DLB (Incidence Rate Ratio = 1.37, p = 0.275). The presence of both delusions (IRR = 2.11, p = 0.01) and depression (IRR = 1.79, p = 0.015) was associated with greater pareidolias. Additionally, overall cognitive dysfunction was associated with pareidolias (IRR = 0.90, p < 0.001). Our findings indicate that pareidolias are associated with poorer cognition and neuropsychiatric dimensions beyond VH, including depression and delusions. As pareidolias have been put forth as a surrogate marker of VH in DLB, future studies examining pareidolias in conjunction with comprehensive psychiatric/cognitive assessment and neuroimaging will further elucidate the clinical utility of pareidolia testing.

Psychopharmacological Medication Use in Frontotemporal Dementia at the Time of Diagnosis: Comparison with Alzheimer's Disease.

Due to the significant presence of neuropsychiatric symptoms in patients with frontotemporal dementia (FTD) spectrum disorders, psychiatric misdiagnoses, diagnostic delay, and use of psychiatric treatments are common prior to the FTD diagnosis. Furthermore, treatment of diagnosed FTD patients mainly relies on off-label psychopharmacological approaches. Currently, limited real-world data are available regarding the actual use of psychopharmacological medications in FTD. To evaluate psychopharmacological medication use at the time of FTD diagnosis. Psychopharmacological medication use was evaluated in a Finnish FTD cohort containing 222 FTD patients, including the major clinical disease phenotypes (behavioral, language, and motor variants) and genetic patients carrying the C9orf72 repeat expansion. A cohort of 214 Alzheimer's disease (AD) patients was used as a neurodegenerative disease reference group. Active use of psychopharmacological medications at the time of diagnosis was significantly more common in FTD compared to AD, especially in the case of antidepressants (26.1% versus 15.0%, OR = 2.01, p = 0.008), antipsychotics (23.9% versus 9.3%, OR = 3.15, p < 0.001), and mood-stabilizers (6.3% versus 1.9%, OR = 2.93, p = 0.085; not statistically significant), whereas the use of cholinesterase inhibitors or memantine was nearly nonexistent in FTD patients. Female gender and behavioral variant of FTD phenotype alongside with depressive and psychotic symptoms were the most prominent factors associating with the use of these medications among the FTD spectrum patients. Use of off-label psychopharmacological medication and polypharmacy is substantially common at the time of FTD diagnosis. This likely reflects the challenges in using symptom-driven treatment approaches, especially prior to the eventual diagnosis.

Safety, tolerability, and preliminary efficacy of SYN120, a dual 5-HT6/5-HT2A antagonist, for the treatment of Parkinson disease dementia: A randomized, controlled, proof-of-concept trial

BackgroundSYN120 is a dual serotonin receptor (5-HT6/5-HT2A) antagonist hypothesized to improve cognition and psychiatric symptoms. ObjectivesWe evaluated the safety, tolerability, and efficacy of SYN120 in patients with Parkinson disease dementia (PDD). MethodsIn a multicenter, double-blind, parallel-group, 16-week phase 2a proof-of-concept trial in PDD with concomitant cholinesterase inhibitor use, eligible patients were randomized to oral SYN120 (100 mg/day) or placebo. Adverse events (AEs), Unified Parkinson's Disease Rating Scale (UPDRS) scores, and discontinuations assessed safety and tolerability. The primary and key secondary efficacy measures were the Cognitive Drug Research (CDR) computerized assessment system Continuity of Attention and Quality of Episodic Memory scores. Other efficacy measures were: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC), Brief Penn Parkinson's Daily Activity Questionnaire-15 (PDAQ-15), Scales for Outcomes in Parkinson's Disease-Sleep Scale (SCOPA-Sleep), and Neuropsychiatric Inventory (NPI). ResultsEighty-two patients were randomized to SYN120 (N = 38) or placebo (N = 44), AEs occurred in 74% and 77% of patients, and treatment discontinuation in both groups was 16%. Nausea and vomiting were more frequent, and motor symptoms (UPDRS) worsened in the SYN120 group. At week 16, the SYN120 and placebo groups did not differ significantly for any cognitive assessment. Cognitive activities of daily living (PDAQ-15) and the NPI-Apathy/Indifference scores improved nominally in the SYN120 group compared with placebo (unadjusted p = 0.029 and 0.028). ConclusionsSYN120 was adequately tolerated, mild worsening of motor symptoms was noted and it did not improve cognition in PDD patients. Its potential benefits for cognitive activities of daily living and apathy warrant further study. RegistrationClinicaltrials.gov as NCT02258152.

Cholinesterase Inhibitors for Treatment of Psychotic Symptoms in Alzheimer Disease and Parkinson Disease

Psychotic symptoms greatly increase the burden of disease for people with neurodegenerative disorders and their caregivers. Cholinesterase inhibitors (ChEIs) may be effective treatment for psychotic symptoms in these disorders. Previous trials only evaluated neuropsychiatric symptoms as a secondary and an overall outcome, potentially blurring the outcomes noted with ChEI use specifically for psychotic symptoms. To quantitatively assess the use of ChEIs for treatment of individual neuropsychiatric symptoms, specifically hallucinations and delusions, in patients with Alzheimer disease (AD), Parkinson disease (PD), and dementia with Lewy bodies (DLB). A systematic search was performed in PubMed (MEDLINE), Embase, and PsychInfo, without year restrictions. Additional eligible studies were retrieved from reference lists. The final search cutoff date was April 21, 2022. Studies were selected if they presented the results of placebo-controlled randomized clinical trials, including at least 1 donepezil, rivastigmine, or galantamine treatment arm in patients with AD, PD, or DLB; if they applied at least 1 neuropsychiatric measure including hallucinations and/or delusions; and if a full-text version of the study was available in the English language. Study selection was performed and checked by multiple reviewers. Original research data were requested on eligible studies. A 2-stage meta-analysis was then performed, using random-effects models. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed for extracting data and assessing the data quality and validity. Data extraction was checked by a second reviewer. Primary outcomes were hallucinations and delusions; secondary outcomes included all other individual neuropsychiatric subdomains as well as the total neuropsychiatric score. In total, 34 eligible randomized clinical trials were selected. Individual participant data on 6649 individuals (3830 [62.6%] women; mean [SD] age, 75.0 [8.2] years) were obtained from 17 trials (AD: n = 12; PD: n = 5; individual participant data were not available for DLB). An association with ChEI treatment was shown in the AD subgroup for delusions (-0.08; 95% CI, -0.14 to -0.03; P = .006) and hallucinations (-0.09; 95% CI, -0.14 to -0.04; P = .003) and in the PD subgroup for delusions (-0.14; 95% CI, -0.26 to -0.01; P = .04) and hallucinations (-0.08, 95% CI -0.13 to -0.03; P = .01). The results of this individual participant data meta-analysis suggest that ChEI treatment improves psychotic symptoms in patients with AD and PD with small effect sizes.

CO203 Cumulative Anticholinergic Burden and Its Predictors Among Older Adults with Alzheimer's Disease Initiating Cholinesterase Inhibitors

Cumulative anticholinergic burden (CAB) focuses on the cumulative effect of multiple medications with anticholinergic properties. However, concomitant use of cholinesterase inhibitors (ChEIs) and CAB can nullify the treatment benefit of ChEIs and worsen Alzheimer's disease (AD). This study evaluates the prevalence and factors associated with CAB among patients with AD initiating ChEIs.

Ethnic Variations in Patient Outcomes in a Memory Clinic Setting Between 2013 and 2021.

The incidence of dementia in Black and Asian populations in the UK is set to rise. There is concern surrounding differences in services provided for different ethnic groups. This study aimed to examine ethnic variations in survival, services accessed, and medication use across White, Black, and Asian groups in routine memory clinic setting. We retrospectively examined referrals to a memory service between 2013 and 2021. A random sample of 104 White, 99 Asian, and 74 Black patients were analyzed for differences in support services, voluntary services, medication use, and survival rate. There were statistically significant differences in survival of the Asian compared to the White group (Hazard ratio (HR = 2.17,95% confidence interval (CI) 1.23-3.85, p = 0.008)) following adjustment for age, gender, diagnosis, cognitive impairment, severity, access to support and voluntary services, and use of cholinesterase inhibitors, N-methyl-D-aspartate antagonists, and antipsychotics. The Asian group showed a statistically significantly reduction in access to support services compared to the White group (HR = 0.05, 95% CI 0.01-0.37, p = 0.003). In contrast, the survival rate was similar between the White and Black dementia patients. We found significantly reduced survival and reduced access to support services in Asian compared to White patients with dementia. Further research is needed to investigate the generalizability of our results, and determine the cause, and consequent remedies of these associations in ethnic minority groups.

Potential revival of cholinesterase inhibitors as drugs in veterinary medicine.

The cholinergic system is involved in the regulation of all organ systems and has acetylcholine (ACh) as almost its only neurotransmitter. Any substance is called cholinergic if it can alter the action of acetylcholine. Cholinesterases (ChEs) are enzymes that enable the hydrolysis of acetylcholine and in this way ensure homeostasis in cholinergic synapses. Cholinesterase inhibitors (ChEi) are a group of indirect-acting cholinergic agonists that influence the activity of the cholinergic system. Several compounds that can inhibit cholinesterases are of importance to veterinary medicine from pharmacological and toxicological perspective. The frequency of their use in veterinary medicine has fluctuated over the years and is now reduced to a minimum. They are mainly used in agriculture as pesticides, and some are rarely used as parasiticides for companion animals and livestock. In recent years, interest in the use of new cholinesterase inhibitors has increased since canine cognitive dysfunction (CCD) became a recognized and extensively studied disease. Similar to Alzheimer's disease (AD) in humans, CCD can be treated with cholinesterase inhibitors that cross the blood-brain barrier. In this review, the mammalian cholinergic system and the drugs that interact with cholinesterases are introduced. Cholinesterase inhibitors that can be used for the treatment of CCD are described in detail.

Association between cholinesterase inhibitors and kidney function decline in patients with Alzheimer’s dementia

Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years (64% women) and the mean eGFR was 68 ml/min/1.73m2. During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of CKD progression (1,231 events, adjusted hazard ratio 0.82; 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression.

Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Psychosis is one of the common psychiatric presentations in the natural course of PD. PD psychosis is an important non-motor symptom, which is strongly correlated with a poor prognosis. Increasing attention is being given to PD psychosis. In this opinion review, we summarized and analyzed the identification, screening, epidemiology, mechanisms, risk factors, and therapeutic approaches of PD psychosis based on the current clinical evidence. PD psychosis tends to have a negative effect on patients' quality of life and increases the burden of family caregiving. Screening and identification in the early stage of disease is crucial for establishing tailored therapeutic strategies and predicting the long-term outcome. Development of PD psychosis is believed to involve a combination of exogenous and endogenous mechanisms including imbalance of neurotransmitters, structural and network changes, genetic profiles, cognitive impairment, and antiparkinsonian medications. The therapeutic strategy for PD psychosis includes reducing or ceasing the use of dopaminergic drug, antipsychotics, cholinesterase inhibitors, and non-pharmacological interventions. Ongoing clinical trials are expected to provide new insights for tailoring therapy for PD psychosis. Future research based on novel biomarkers and genetic factors may help inform individualized therapeutic strategies.

Pharmacotherapy of Alzheimer's disease: an overview of systematic reviews.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. In this umbrella systematic review (SR), we summarized the efficacy of different pharmacological interventions in improving cognitive function in patients with AD. A systematic search was performed through the PubMed, Scopus, Embase, and Cochrane databases for SRs of studies assessing the efficacy of pharmacological interventions versus placebo in improving cognitive function in AD or mild cognitive impairment due to AD. The risk of bias (RoB) was assessed using the Risk of Bias in SRs (ROBIS) tool. Out of 1748 articles found through the database survey, 33 SR articles were included. These studies assessed effects of immunotherapy, cholinesterase inhibitors (ChEIs), memantine, statins, lithium, nonsteroidal anti-inflammatory drugs (NSAIDs), antidiabetic agents, Cerebrolysin, RAS-targeting antihypertensive drugs (ARBs and ACEIs), psychostimulants, glycogen synthase kinase 3 (GSK-3) inhibitors, melatonin, and herbal medications on cognitive function in AD patients. There was no notable overall RoB in 18 studies (54.5%), the RoB in 14 studies (42.4%) was high, and in one study (3.0%) it was unclear. The use of ChEIs, including rivastigmine, galantamine, and donepezil, as well as memantine has demonstrated a positive impact on improving cognitive outcomes of AD patients, but no considerable effects were found for immunotherapies. Melatonin, statins, antihypertensive drugs, antidiabetic agents, Cerebrolysin, psychostimulants, and some herbal drugs such as Danggui-Shaoyao-San and Ginkgo biloba seem to be effective in improving cognitive function of AD patients, but the evidence in this regard is limited.

MSR65 Comparison of Machine Learning Approach with Traditional Method to Predict Risk of Serious Events Associated with Individual Cholinesterase Inhibitors Use in Older Adults with Dementia

Machine learning techniques have been recommended as promising alternatives to logistic regression for the estimation of propensity scores. This study compared the performance of the machine learning approach Inverse Probability Weighting- Gradient Boosted Modeling (IPTW-GBM) with traditional Propensity Scores (PS) method in predicting risk of serious events across individual Cholinesterase inhibitors (ChEIs) use in older adults with dementia.

P20 Risk of Antimuscarinic Initiation with Cholinesterase Inhibitor Use in Patients with Alzheimer's Disease

Antimuscarinic use in Alzheimer’s disease (AD) is a significant concern as it can worsen cognition due to its anticholinergic effects. This study evaluated the risk of antimuscarinic initiation with the use of individual Cholinesterase Inhibitors (CHEIs) in patients with AD.

RWD18 Sex-Based Differences in Risk of Serious Events with Individual Cholinesterase Inhibitors Use in Older Adults with Dementia: A Medicare Study

There is limited research evaluating the safety of Cholinesterase inhibitors (ChEIs) based on real-world data. Additionally, the moderating effect of sex on outcomes is not well-studied in dementia. This study evaluated the sex-based effects on the risk of serious events with individual ChEIs in older adults with dementia.

EPH163 Risk of Memantine Initiation with Use of Antimuscarinics and/or Cholinesterase Inhibitors in Older Adults with Alzheimer's Disease

Antimuscarinic use along with cholinesterase inhibitors (CHEIs) can nullify the modest treatment benefit of CHEIs and can worsen Alzheimer’s disease (AD) due to therapeutically opposing mechanisms of action. This worsening of cognition can precipitate prescribing of memantine for moderate-to-severe AD. Therefore, this study assessed the risk of memantine initiation in older adults with AD using antimuscarinics and CHEIs.

Risk factors for hospital-acquired pneumonia among inpatients with mental disorders in a large mental health center within a tertiary general hospital

Few researchers have investigated the incidence of and risk factors for hospital-acquired pneumonia (HAP) among inpatients with mental disorders in a general hospital. This study included patients with mental disorders hospitalized in a large mental health center (situated in a general hospital) between January 1, 2017, and July 31, 2021 (excluding January 1, 2020- May 31, 2020). Risk factors for HAP were identified by logistic regression analysis after propensity score matching (PSM, 1:4) for gender, age, duration of observation, and hospital ward. The study included 16,864 patients. HAP incidence rate was 1.15% overall, 2.11% in closed wards, 0.75% in open wards, 4.45% in patients with organic mental disorders, 1.80% in patients with schizophrenia spectrum disorders, and 0.84% in patients with mood disorders. Risk factors for HAP after PSM were hypoproteinemia, chronic liver disease, use of clozapine, hospitalization during the previous 180 days, body mass index (BMI) ≤18.5 kg/m2, cholinesterase inhibitor use, and mood stabilizer use. HAP was common among inpatients with mental disorders. Risk factors for HAP in patients with mental disorders include hypoproteinemia, chronic liver disease, hospitalization during the past 180 days, BMI ≤18.5 kg/m2, and use of clozapine, cholinesterase inhibitors, or mood stabilizers.