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Background: To analyze and compare the pharmacological treatments for Alzheimer disease (AD), we will conduct a systematic review and network meta-analysis focusing on their efficacy and safety over a duration exceeding 1 year., Methods: We searched the databases of PubMed, Scopus, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and CNKI until July 30, 2023, for randomized controlled trials (RCTs) evaluating pharmacological treatments for AD., Results: Seventeen RCTs, comprising 7214 participants, investigated the efficacy of the following drugs: Donepezil, Rivastigmine, Galantamine, Memantine, Ginkgo biloba extract (EGb), Atorvastatin-calcium and Vitamin B in the treatment of AD. The network meta-analysis resulted indicated that placebo demonstrated greater effectiveness compared to Atorvastatin-calcium 80 mg (mean different [MD] = -6.93, confidence interval [CI] -11.57, -2.29) and Rivastigmine 12 mg (MD = -3.33, CI -6.56, -0.09). EGb120 mg exhibited a greater improvement in cognition compared to Atorvastatin-calcium 80 mg (MD = 7.77, CI 2.07, 13.46) and Rivastigmine 12 mg + EGb120 mg (MD = 9.92, CI 1.32, 17.22). EGb 120 mg emerged as the most efficient intervention for cognition, while placebo demonstrated the least harm over a period exceeding 1 year., Conclusions: In this network meta-analysis of studies of patients with AD and a follow-up period of at least 1 year, EGb 120 mg demonstrated cognitive benefits, while placebo posed the least harm for AD. More RCTs are required to address the uncertainty surrounding the efficacy of medication., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial., Objective: The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis., Methods: We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results., Results: All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs., Conclusion: ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To examine the real-world effects of the cholinesterase inhibitors (AChEI) on all-cause mortality. A nationwide, retrospective cohort study. Participants were diagnosed with incident AD in Denmark from January 1, 2000 to December 31, 2011 with follow-up until December 31, 2012. A total of 36,513 participants were included in the current study with 22,063 deaths during 132,426 person-years of follow-up. At baseline, patients not treated with AChEI (n = 28,755 [9961 males (35%)]) had a mean age ± standard deviation (SD) of 80.33 ± 7.98 years (78.97 ± 8.26 for males and 81.04 ± 7.98 for females), as compared to 79.95 ± 7.67 (78.87 ± 7.61 for males and 80.61 ± 7.63 for females) in the group exposed at baseline. Patients treated with AChEI had a beneficial hazard ratio (HR) of 0.69, 95% confidence interval (CI) (0.67-0.71) for all-cause mortality as compared to patients not treated, with donepezil (HR 0.80, 95% CI [0.77-0.82]) and galantamine (HR 0.93,95% CI [0.89-0.97]) having beneficial effects on mortality rate as compared to non-treatment, whereas rivastigmine (HR 0.99, 95% CI [0.95-1.03]) was associated with a mortality rate comparable to non-treatment with AChEI. Patients were primarily exposed to donepezil (65.8%) with rivastigmine (19.8%) and galantamine (14.4%) being used less often. These findings underscore the effect of AChEI on not only reducing speed of cognitive decline but also directly prolonging life, which could result in changes in treatment recommendation for when to stop treatment., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The aim of this study was to explore the effect of rivastigmine on brain function in Alzheimer disease (AD) by analyzing brain functional network based on the graph theory., Methods: We enrolled 9 patients with mild to moderate AD who received rivastigmine treatment and 9 healthy controls (HC). Subsequently, we used resting-state functional magnetic resonance imaging data to establish the whole-brain functional network using a graph theory-based analysis. Furthermore, we compared systemic and local network indicators between pre- and posttreatment., Results: Patients with AD exhibited a posttreatment increase in the Mini-Mental State Examination scores and a decrease in the Alzheimer's Disease Assessment Scale cognitive subscale scores and activities of daily living. The systemic network for HC and patients with AD had good pre- and posttreatment clustering coefficients. There was no change in the Cp, Lp, Gamma, Lambda, and Sigma in patients with AD. There were no significant between-group differences in the pre- and posttreatment systemic network measures. Regarding the regional network, patients with AD showed increased betweenness centrality in the bilateral caudate nucleus and right superior temporal pole after treatment with rivastigmine. However, there was no between-group difference in the pre- and posttreatment betweenness centrality of these regions. There were no significant correlations between regional network measure changes and clinical score alterations in patients with AD., Conclusions: There are similar systemic network properties between patients with AD and HC. Rivastigmine cannot alter systemic network attributes in patients with AD. However, it improves the topological properties of regional networks and between-node information transmission in patients with AD., Competing Interests: Conflicts of Interest and Source of Funding: This work was funded by grants from the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2015KYB073), the Traditional Chinese Medicine Technology Project of Zhejiang Province (2015ZA018) to Jiangtao Zhang, and the Project of Basic Public Welfare Research of Zhejiang (LGF18H090021) to Jianan Cheng. The authors have no conflicts of interest to declare., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Dementia with Lewy bodies (DLB) is the second most common dementia. Features of DLB include postganglionic cardiac sympathetic denervation and autonomic instability. Rivastigmine therapy, an acetylcholinesterase inhibitor, is widely used in the primary treatment of DLB; however, the cardiovascular safety and tolerability of transdermal rivastigmine needs to be reviewed., Objective: To evaluate whether transdermal rivastigmine has an effect on blood pressure, heart rate, and electrocardiography measurements., Materials and Methods: A total of 722 patients diagnosed with dementia were retrospectively screened. Fifty-seven of 98 DLB patients who received transdermal rivastigmine treatment with available serial electrocardiography and blood pressure measurements were included in the study. Baseline and follow-up measurements were compared for patients on the 9.5 to 13.3 mg/d rivastigmine dose for at least 4 weeks., Results: The mean age of the patients was 80.77±6.04, and the majority were women (63%). A total of 8 cases with bradycardia and 5 with orthostatic hypotension were detected during follow-up, and rivastigmine patch was stopped in one of those 8 patients due to symptomatic bradycardia. Nonetheless, there was no difference between baseline and follow-up measurements of the patients, including heart rate, cardiac rhythm, electrocardiographic intervals, blood pressure, pulse pressure, and postural blood pressure changes., Conclusions: Transdermal rivastigmine therapy is not associated with arrhythmogenic or hypotensive effects in the elderly patients with DLB. However, when prescribing transdermal rivastigmine, physicians should pay attention to newly emerging orthostatic hypotension during the follow-up in these patients.

Pisa syndrome (PS) is a state of dystonic muscle contraction with a marked truncal deviation to one side. It is an uncommon adverse effect of antipsychotic drugs, but is rarely reported in patients receiving acetylcholinesterase inhibitors, especially rivastigmine. We present a 57-year-old female patient with Alzheimer disease who began to develop symptoms of dementia at the age of 51 years. She was observed to have symptoms of PS after continuous use of rivastigmine (9 mg/d) for nearly 2 years. The PS symptoms improved after the dose of rivastigmine was reduced but recurred when the dose was added back to 9 mg/d. Finally, after we decreased the dose to 4.5 mg/d, her PS symptoms were remitted. This report reminds us that clinicians need to be cautious about the risk of PS when prescribing rivastigmine in a patient with early-onset Alzheimer disease.

The long-term safety, tolerability, and efficacy of high-dose 13.3 mg/24 h rivastigmine patch in severe Alzheimer disease was evaluated in a 24-week, open-label extension to the double-blind ACTION study. Safety and tolerability, and efficacy on the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV), Severe Impairment Battery (SIB), and ADCS-Clinical Global Impression of Change (ADCS-CGIC) were assessed. Overall, 197 patients continued on 13.3 mg/24 h patch; 199 uptitrated from 4.6 mg/24 h to 13.3 mg/24 h patch. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar in patients who continued on, and patients who uptitrated to, 13.3 mg/24 h patch (AEs: 57.9% and 59.8%; serious AEs: 16.2% and 16.1%; discontinuations: 11.2% and 12.1%, respectively). Larger mean changes from double-blind baseline were observed in patients uptitrated on the ADCS-ADL-SIV (-4.6; SD=8.7) and SIB (-7.0; SD=16.6), than those who continued on 13.3 mg/24 h patch (-3.9; SD=8.0 and -4.7; SD=16.8, respectively). ADCS-CGIC scores were comparable. There were no clinically relevant between-group differences in safety and tolerability. Greater decline was observed in patients with delayed uptitration to high-dose 13.3 mg/24 h patch than patients who continued on high-dose patch.