Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non‐hypertensive Alzheimer's patients

Al-Hamed, Faez Saleh; Kouniaris, Stamatis; Tamimi, Iskandar; Lordkipanidzé, Marie; Madathil, Sreenath; Kezouh, Abbas; Karp, Igor; Nicolau, Bélinda; Tamimi, Faleh

doi:10.1002/trc2.12184

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…However, there was no association between ChEIs and increased risk of urinary incontinence [ 8 ]. Additionally, AChEI uses were associated with an increased risk of angina, myocardial infarction, and stroke [ 9 ]. Therefore, close monitoring is required.…”

Section: Reviewmentioning

confidence: 99%

A Review of Recent Advances in the Management of Alzheimer’s Disease

Thangwaritorn,

Lee,

Metchikoff

et al. 2024

Cureus

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Alzheimer’s disease (AD) is the most common neurodegenerative condition and a form of dementia encountered in medical practice. Despite many proposed and attempted treatments, this disease remains a major puzzle in the public health systems worldwide. The initial part of this article provides an overview and illustration of the primary mechanisms responsible for neuronal damage in AD. Subsequently, it offers a critical evaluation of the most noteworthy studies on pharmacological therapy for AD and outlines recent advancements and novel approaches to managing this condition. Main properties, categorization, Food and Drug Administration (FDA) status, mechanisms of action, benefits, and common side effects of the classical and the most recently proposed pharmacological treatments for AD are described. The conventional pharmacological agents revised comprise cholinesterase inhibitors, monoclonal antibodies, and other therapies, such as memantine, valproic acid, and rosiglitazone. The innovative reviewed pharmacological agents comprise the monoclonal antibodies: donanemab, gantenerumab, solanezumab, bapineuzumab, crenezumab, and semorinemab. Nutritional supplements such as alpha-tocopherol (vitamin E) and caprylidene are also revised. Tau and amyloid-targeting treatments include methylthioninium moiety (MT), leuco-methylthioninium bis (LMTM), an oxidized form of MT, and tramiprosate, which inhibits the beta-amyloid (Aβ) monomer aggregation into toxic oligomers. Antidiabetic and anti-neuroinflammation drugs recently proposed for AD treatment are discussed. The antidiabetic drugs include NE3107, an anti-inflammatory and insulin sensitizer, and the diabetes mainstream drug metformin. The anti-neuroinflammatory AD therapies include the use of sodium oligomannate (GV-971), infusions with intravenous immunoglobulin aiming to decrease plasma levels of the constituents of Aβ plaques, and masitinib, a tyrosine kinase inhibitor that impacts mast and microglia cells. Additional anti-inflammatory agents being currently tested in phase-2 clinical trials, such as atomoxetine (selective norepinephrine reuptake inhibitor), losartan (angiotensin 2 receptor agonist), genistein (anti-inflammatory isoflavone neuroprotective agent), trans-resveratrol (polyphenol antioxidant plant estrogen), and benfotiamine (synthetic thiamine precursor), were reviewed. Lastly, drugs targeting Alzheimer's-associated symptoms, such as brexpiprazole (serotonin dopamine activity modulator) and suvorexant (orexin receptor antagonist), respectively, used for agitation and insomnia in AD patients, are reviewed. As experimental investigations and clinical research progress, there is a possibility that a combination of newly tested medications and traditional ones may emerge as a promising treatment option for AD in the future.

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Section: Reviewmentioning

confidence: 99%

A Review of Recent Advances in the Management of Alzheimer’s Disease

Thangwaritorn,

Lee,

Metchikoff

et al. 2024

Cureus

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“…A common research area of Electronic Health Records (EHRs) research, including the use of CPRD, is the effect of diseases on mortality and it is therefore imperative to understand how mortality rates in a selected CPRD population compare with general population rates. The selection of cohorts on the requirement of individuals having been registered at a contributing GP practice for a specific length of time is commonplace within EHR research [5][6][7][8][9][10]. Sometimes referred to as research-quality follow-up, or lookback window, it is an observation period prior to the start of a subject's at-risk follow-up, ending at a date often referred to as the index date.…”

Section: Introductionmentioning

confidence: 99%

Patterns of rates of mortality in the Clinical Practice Research Datalink

et al. 2022

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The Clinical Practice Research Datalink (CPRD) is a widely used data resource, representative in demographic profile, with accurate death recordings but it is unclear if mortality rates within CPRD GOLD are similar to rates in the general population. Rates may additionally be affected by selection bias caused by the requirement that a cohort have a minimum lookback window, i.e. observation time prior to start of at-risk follow-up. Standardised Mortality Ratios (SMRs) were calculated incorporating published population reference rates from the Office for National Statistics (ONS), using Poisson regression with rates in CPRD GOLD contrasted to ONS rates, stratified by age, calendar year and sex. An overall SMR was estimated along with SMRs presented for cohorts with different lookback windows (1, 2, 5, 10 years). SMRs were stratified by calendar year, length of follow-up and age group. Mortality rates in a random sample of 1 million CPRD GOLD patients were slightly lower than the national population [SMR = 0.980 95% confidence interval (CI) (0.973, 0.987)]. Cohorts with observational lookback had SMRs below one [1 year of lookback; SMR = 0.905 (0.898, 0.912), 2 years; SMR = 0.881 (0.874, 0.888), 5 years; SMR = 0.849 (0.841, 0.857), 10 years; SMR = 0.837 (0.827, 0.847)]. Mortality rates in the first two years after patient entry into CPRD were higher than the general population, while SMRs dropped below one thereafter. Mortality rates in CPRD, using simple entry requirements, are similar to rates seen in the English population. The requirement of at least a single year of lookback results in lower mortality rates compared to national estimates.

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Patterns of rates of mortality in the Clinical Practice Research Datalink

Schmidt

Lambert

Gillies

et al. 2022

Preprint

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Introduction: The Clinical Practice Research Datalink (CPRD) is a widely used data resource, representative in demographic profile, with accurate death recordings but it is unclear if mortality rates within CPRD are similar to rates in the general population. Rates may additionally be affected by selection bias caused by the requirement that a cohort have a minimum lookback window, i.e. observation time prior to start of at-risk follow-up. Methods: Standardised Mortality Ratios (SMRs) were calculated incorporating published population reference rates from the Office for National Statistics (ONS), using Poisson regression with rates in CPRD contrasted to ONS rates, stratified by age, calendar year and sex. An overall SMR was estimated along with SMRs presented for cohorts with different lookback windows (1, 2, 5, 10 years). SMRs were stratified by calendar year, length of follow-up and age group. Results: Mortality rates in a random sample of 1 million CPRD GOLD patients were slightly lower than the national population [SMR=0.980 95% confidence interval (CI) (0.973, 0.987)]. Cohorts with observational lookback had SMRs below one [1 year of lookback; SMR=0.905 (0.898, 0.912), 2 years; SMR=0.881 (0.874, 0.888), 5 years; SMR=0.849 (0.841, 0.857), 10 years; SMR=0.837 (0.827, 0.847)]. Mortality rates in the first two years after patient entry into CPRD were higher than the general population, while SMRs dropped below one thereafter. Conclusion: Mortality rates in CPRD, using simple entry requirements, are similar to rates seen in the English population. The requirement of at least a single year of lookback results in lower mortality rates compared to national estimates.

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Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non‐hypertensive Alzheimer's patients

Cited by 3 publications

References 42 publications

A Review of Recent Advances in the Management of Alzheimer’s Disease

A Review of Recent Advances in the Management of Alzheimer’s Disease

Patterns of rates of mortality in the Clinical Practice Research Datalink

Patterns of rates of mortality in the Clinical Practice Research Datalink

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