Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer’s dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial

Abstract

Background and objectiveStudies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer’s disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs.MethodsThree hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study.ResultsOf the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups.ConclusionsAlthough the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs.Trial registrationClinicalTrials.gov NCT01380288

Therapeutic Potential of Allicin and Aged Garlic Extract in Alzheimer’s Disease

“…Cholinesterase inhibitors (ChEIs) block these enzymes, resulting in greater ACh levels and a transient alleviation in AD symptoms. Therefore, increasing synaptic ACh concentrations with ChEIs, such as donepezil, rivastigmine and galantamine, is the main current pharmacological therapy for AD patients [58,59]. Unfortunately, these medications, as well as memantine, which decreases glutamate excitotoxicity, only provide symptomatic alleviation and do not slow disease progression; thus, the development of new therapeutic approaches is required.…”

The Development of Pharmacological Therapies for Alzheimer’s Disease

“…Rivastigmine, which inhibits both AChE and butyrylcholinesterase (BuChE), should provide more benefits to patients with concurrent vascular disease, which was confirmed in a randomized clinical trial in AD patients with or without vascular risk factors [ 60 ]. However, the conclusions have been controversial, as another trial showed that 24-week treatment with a transdermal rivastigmine patch improved frontal lobe function in AD patients with mild, but not moderate, white matter hyperintensities (WMH), suggesting that less AD pathology and more vascular pathology may attenuate the response to AChEIs [ 61 ]. The transdermal patch may be able to replace oral capsules, with higher tolerability and fewer treatment-related adverse events including gastrointestinal (GI) side effects [ 62 ].…”

An update on the safety of current therapies for Alzheimer’s disease: focus on rivastigmine

“…In fact, adverse skin reactions reports are shown to be more frequent in naturalistic open-label studies or those lacking doubleblinding, hence the importance of the study design in minimizing any risk of bias. [39][40][41][42][43] Educating patients and caregivers at the time of patch prescription about the characteristics of benign versus serious skin reactions contributes to decreasing the rate of patch discontinuation with non-allergic skin lesions, in which case the advantages of continued adherence outweigh the risks. They also need to know that dermatitis is manageable with cold compresses, moisturizing cream and/or topical corticosteroids, and is often preventable by avoiding alcohol or soap use on the skin immediately before patch application, changing the application site every day, alternating between the upper back and lower back, chest, shoulders and upper arms, which are thought to be associated with the least skin irritation, removing the patch gently and moisturizing the skin afterwards.…”

“…In fact, adverse skin reactions reports are shown to be more frequent in naturalistic open-label studies or those lacking double-blinding, hence the importance of the study design in minimizing any risk of bias. 39–43…”