Evaluating Response to High‐Dose 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer's Disease

Farlow, Martin R.; Sadowsky, Carl; Velting, Drew M.; Meng, Xiangyi; Islam, Muhammad

doi:10.1111/cns.12385

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…Three studies by Wattmo found mean higher doses of AChEI to be related to cognitive and functional response at 6 months and 3 years in a large sample of Swedish AD patients (Wattmo et al, 2011 , 2012 ; Wattmo and Wallin, 2017 ). A post-hoc analysis of a RCT by Farlow found that patients with severe AD on rivastigmine patch 13.3 mg/day exhibited better response on the ADAS-Clinical Global Impression of Change (ADAS-CGIC) at 6 months compared to patients on rivastigmine patch 4.6 mg/day (Farlow et al, 2015 ). Another more recent post-hoc analysis of the OPTIMA study, performed by Molinuevo, found that patients with moderate AD on rivastigmine patch 13.3 mg/day were more likely to exhibit cognitive and functional response at 12 months compared to subjects on rivastigmine patch 9.5 mg/day.…”

Section: Discussionmentioning

confidence: 99%

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Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review

et al. 2022

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BackgroundThe mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results.MethodsWe conducted a systematic review of the literature up to December 31st, 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string: predict*AND respon*AND (acetylcholinesterase inhibitors OR donepezil OR rivastigmine OR galantamine). The results were presented narratively.ResultsWe identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included.DiscussionThe studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial.

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Section: Discussionmentioning

confidence: 99%

“…A study by Cheng found younger age to be predictive of more rapid cognitive decline in Taiwanese AD patients on AChEI (Cheng et al, 2015 ). A post-hoc analysis of a RCT by Farlow found increased age to be a predictor of response to rivastigmine at 6 months; moreover, older patients experienced less adverse events (Farlow et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review

et al. 2022

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“…ChEis are approved for the treatment of mild and moderate AD dementia. In addition, donepezil and rivastigmine are also approved for use in severe stage of AD dementia 12,13 15 .…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…The pathological damage caused by the tau-containing neurofibrillary tangles (NFT) in the nucleus basalis of Meynert (nbM) might be a critical element determining this response. Depending on the involvement of the lim- 12,13 AChE: acetylcholinesterase, BChE: butyrylcholinesterase bic structures (including the nbM), three different subtypes of AD were described: (1) hippocampal sparing (relatively spared hippocampal formation compared to the neocortex), (2) limbic predominant (severely involved hippocampus compared to the relatively spared neocortex) and (3) typical AD pattern, where NFT pathology is balanced between the two forms. Greater NFT accumulation and the lowest number of surviving nbM neurons were observed in the hippocampal sparing type, compared to the typical AD and limbic predominant subtypes 17 .…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Cholinesterase inhibitors and memantine for the treatment of Alzheimer and non-Alzheimer dementias

2021

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In aging societies, the morbidity and mortality of dementia is increasing at a significant rate, thereby imposing burden on healthcare, economy and the society as well. Patients’ and caregivers’ quality of life and life expectancy are greatly determined by the early diagnosis and the initiation of available symptomatic treatments. Cholinesterase inhibitors and memantine have been the cornerstones of Alzheimer’s therapy for approximately two decades and over the years, more and more experience has been gained on their use in non-Alzheimer’s dementias too. The aim of our work was to provide a comprehensive summary about the use of cholinesterase inhibitors and memantine for the treatment of Alzheimer’s and non-Alzheimers’s dementias.

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“…A higher dose or a combined treatment may have better clinical outcomes. For instance, in the ACTION trial, when comparing the effects of the lowest and highest doses in treating patients with severe AD for 24 weeks, the highest dose demonstrated better outcomes in the prospective and retrospective analyses [63][64][65]. A 6-month combined treatment with a rivastigmine patch (9.5 mg/24 h) and a cognition-focused intervention in a cohort of a population with severe AD, on the other hand, demonstrated superior efficacy compared with rivastigmine treatment alone [66].…”

Section: Symptomatic Treatments Based On the Cholinergic Hypothesismentioning

confidence: 99%

The Development of Pharmacological Therapies for Alzheimer’s Disease

et al. 2021

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. The aged population is growing globally, creating an urgent need for more promising therapies for this debilitating disease. Much effort has been made in recent decades, and the field is highly dynamic, with numerous trials. The main focus of these trials includes disease modification and symptomatic treatment. Some have shown beneficial outcomes, while others have shown no significant benefits. Here, we cover the outcome of recently published AD clinical trials, as well as the mechanism of action of these therapeutical agents, to re-think drug development strategies and directions for future studies.

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Evaluating Response to High‐Dose 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer's Disease

Cited by 12 publications

References 23 publications

Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review

Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review

Cholinesterase inhibitors and memantine for the treatment of Alzheimer and non-Alzheimer dementias

The Development of Pharmacological Therapies for Alzheimer’s Disease

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