Could cholinesterase inhibitors be harmful over the long term?

Schneider, Lon S.

doi:10.1017/s1041610211002389

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…They also contain the potential for substantial risk that erroneous conclusions about both efficacy and tolerability could be made. [16][17][18][19][20] A manual search of included references was completed to supplement the database search.…”

Section: Methodsmentioning

confidence: 99%

Current Practices in the Treatment of Alzheimer Disease: Where is the Evidence After the Phase III Trials?

Ehret

Chamberlin

2015

Clinical Therapeutics

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Section: Methodsmentioning

confidence: 99%

Current Practices in the Treatment of Alzheimer Disease: Where is the Evidence After the Phase III Trials?

Ehret

Chamberlin

2015

Clinical Therapeutics

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“…Cholinesterase inhibitors have consistently shown a symptomatic benefit in mild to severe dementia due to AD in randomized, double-blind, placebo-controlled trials (Birks, 2006). It has, however, been questioned whether long-term treatment with ChEIs could be harmful (Schneider, 2012). A recent metaanalysis found that AD patients treated with symptomatic treatments had a faster rate of cognitive decline (Kennedy et al, 2018).…”

Section: Symptomatic Medications For Alzheimer Disease and Cognitive mentioning

confidence: 99%

Statistical Disease Progression Modeling in Alzheimer Disease

Rakêt

2020

Front. Big Data

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Background: The characterizing symptom of Alzheimer disease (AD) is cognitive deterioration. While much recent work has focused on defining AD as a biological construct, most patients are still diagnosed, staged, and treated based on their cognitive symptoms. But the cognitive capability of a patient at any time throughout this deterioration reflects not only the disease state, but also the effect of the cognitive decline on the patient's pre-disease cognitive capability. Patients with high pre-disease cognitive capabilities tend to score better on cognitive tests that are sensitive early in disease relative to patients with low pre-disease cognitive capabilities at a similar disease stage. Thus, a single assessment with a cognitive test is often not adequate for determining the stage of an AD patient. Repeated evaluation of patients' cognition over time may improve the ability to stage AD patients, and such longitudinal assessments in combinations with biomarker assessments can help elucidate the time dynamics of biomarkers. In turn, this can potentially lead to identification of markers that are predictive of disease stage and future cognitive decline, possibly before any cognitive deficit is measurable. Methods and Findings: This article presents a class of statistical disease progression models and applies them to longitudinal cognitive scores. These non-linear mixed-effects disease progression models explicitly model disease stage, baseline cognition, and the patients' individual changes in cognitive ability as latent variables. Maximum-likelihood estimation in these models induces a data-driven criterion for separating disease progression and baseline cognition. Applied to data from the Alzheimer's Disease Neuroimaging Initiative, the model estimated a timeline of cognitive decline that spans ∼15 years from the earliest subjective cognitive deficits to severe AD dementia. Subsequent analyses demonstrated how direct modeling of latent factors that modify the observed data patterns provides a scaffold for understanding disease progression, biomarkers, and treatment effects along the continuous time progression of disease. Conclusions: The presented framework enables direct interpretations of factors that modify cognitive decline. The results give new insights to the value of biomarkers for staging patients and suggest alternative explanations for previous findings related to accelerated cognitive decline among highly educated patients and patients on symptomatic treatments.

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“…Even worse, Sona et al (2012) showed, through a follow-up of 18 months, that the long-term use of cholinesterase inhibitors was associated with a higher risk of rapid cognitive decline in people with a diagnosis of AD. Of note is that cholinesterase inhibitors have also been associated with other adverse effects, in particular, a higher rate of bradycardia, syncope, insertion of a pacemaker, and hip fracture (Schneider, 2012). In addition, a meta-analysis and systematic review conducted by Tricco et al (2013) showed that cholinesterase inhibitors and memantine did not improve cognitive abilities or functional status of individuals with MCI.…”

Section: Another Approach To Alzheimer's Disease and Another Researchmentioning

confidence: 99%

A life-course and multifactorial approach to Alzheimer’s disease: Implications for research, clinical assessment and intervention practices

Linden

2016

Dementia

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According to the dominant biomedical view, Alzheimer's disease (AD) has a precise, necessary and unifying neurobiological cause, which distinguishes it from other neurodegenerative diseases and normal ageing. However, different types of evidence specifically lead to questioning the foundations of this essentialist and category-based approach to AD. It seems more and more evident that AD represents a heterogeneous state, determined by multiple factors and mechanisms that interact and intervene throughout life. This other way of conceiving AD not only requires a change of research objectives, but also a profound modification of clinical assessment and intervention practices. It also appeals to follow the path of prevention.

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Could cholinesterase inhibitors be harmful over the long term?

Cited by 10 publications

References 28 publications

Current Practices in the Treatment of Alzheimer Disease: Where is the Evidence After the Phase III Trials?

Current Practices in the Treatment of Alzheimer Disease: Where is the Evidence After the Phase III Trials?

Statistical Disease Progression Modeling in Alzheimer Disease

A life-course and multifactorial approach to Alzheimer’s disease: Implications for research, clinical assessment and intervention practices

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