Defining Treatment Response to Donepezil in Alzheimer’s Disease

Burns, Alistair; Yeates, Andrew; Akintade, Latif; Valle, Megan del; Zhang, Richard Y.; Schwam, Elias; Perdomo, Carlos

doi:10.2165/00002512-200825080-00007

Cited by 26 publications

(13 citation statements)

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“…Current treatments for AD are unable to cure or halt the progress of the disease, and have only mixed results in alleviating the symptoms. The most commonly used medication, Donepezil, shows some benefit for 20%–60% of patients, 1 but a substantial and marked benefit for only 2.3%. 2 However, a long-term study showed no significant benefit compared to placebo for improving daily living functions of Alzheimer’s patients, 3 and many patients discontinue it due to severe side effects.…”

Section: Introductionmentioning

confidence: 99%

“…2 However, a long-term study showed no significant benefit compared to placebo for improving daily living functions of Alzheimer’s patients, 3 and many patients discontinue it due to severe side effects. 1 , 2 This study investigates a new protocol on the use of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for AD. rTMS is a technique that has been successfully used to treat the symptoms of various neurological and psychiatric disorders, including depression, schizophrenia, and Parkinson’s disease.…”

Section: Introductionmentioning

confidence: 99%

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Short and Long-term Effects of rTMS Treatment on Alzheimer's Disease at Different Stages: A Pilot Study

2015

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Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic coil to induce an electric field in brain tissue. As a pilot study, we investigated the effect of rTMS treatment on 10 volunteers with Alzheimer’s disease (AD) in a two-stage study. The first stage consisted of a double-blind crossover study with real and sham treatments. Each treatment block consisted of 13 sessions over 4 weeks. During each session, 2000 TMS pulses at 90%–100% of resting motor threshold were applied to dorsolateral prefrontal cortex bilaterally, and the patients were kept cognitively active by object/action naming during the treatment. The second stage was an open-label study, in which the same treatments were performed in 2-week blocks (10 sessions) approximately every 3 months as follow-up treatments on six of the volunteers, who completed the first stage of the study. Primary outcome measures were the Montreal Cognitive Assessment (MOCA) and the Alzheimer’s Disease Assessment Scale-cognitive subscale. The secondary outcome measures were the Revised Memory and Behavior Checklist as well as our team’s custom-designed cognitive assessments. The results showed a noticeably stronger improvement on all assessments during the real treatment as compared to the sham treatment. The changes in MOCA scores as well as our designed cognitive assessment were found to be statistically significant, with particularly strong results in the six volunteers who were in the early stages of the disease. The long-term trends observed in the second stage of the study also showed generally less decline than would be expected for their condition. It appears that rTMS can be an effective tool for improving the cognitive abilities of patients with early to moderate stages of AD. However, the positive effects of rTMS may persist for only up to a few weeks. Specific skills being practiced during rTMS treatment may retain their improvement for longer periods.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short and Long-term Effects of rTMS Treatment on Alzheimer's Disease at Different Stages: A Pilot Study

2015

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“…Patients who ‘respond’ to treatment are generally regarded as those who demonstrate a clinically meaningful benefit on an outcome measure. In neurodegenerative diseases, a treatment response refers to short-term improvement, longer-term stabilization or a slowed decline in one or more clinically relevant symptom domains [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch

et al. 2015

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IntroductionOPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer’s disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer’s disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48 weeks of double-blind treatment, high-dose patch produced greater functional and cognitive benefits compared with 9.5 mg/24 h patch.MethodsUsing OPTIMA data, a post-hoc responder analysis was performed to firstly, compare the proportion of patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus 9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of decline. ‘Improvers’ were patients who improved on the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) by ≥4 points from baseline, and did not decline on the instrumental domain of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale (ADCS-IADL). ‘Non-decliners’ were patients who did not decline on either scale.ResultsOverall, 265 patients randomized to 13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the intention-to-treat population and were included in the analyses. Significantly more patients were ‘improvers’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10 (3.7%); P = 0.023). A significantly greater proportion of patients were ‘non-decliners’ with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71 (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of 13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind baseline did not consistently predict effects at Weeks 24 or 48.ConclusionMore patients with mild-to-moderate Alzheimer’s disease who are titrated to 13.3 mg/24 h rivastigmine patch at time of decline are ‘improvers’ or ‘non-decliners’ i.e. show responses on cognition and activities of daily living compared with patients remaining on 9.5 mg/24 h patch.Trial registrationClinicaltrials.gov identifier: NCT00506415; registered July 20, 2007.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-014-0088-8) contains supplementary material, which is available to authorized users.

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“…Although the donepezil has been clinically recognized to stabilize cognition for 6 to 12 months, a large proportion of AD patients experience cognitive decline even after the initial intervention. 2 Possibly the reason for these differences in treatment responsiveness are due to various factors such as racial, ethnic, genotype disparities, clinical stage of dementia, co-morbidities, concomitant medication, functional and structural neuronal substrates. 2 3 4 5 However, fundamental reason for this variability is not well understood, but this is essential for understanding etiologies of AD and enhancing effective strategies for management of AD.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Treatment Response to Donepezil using Automated Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease

Kim

Jeong

et al. 2017

Psychiatry Investig

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Previous studies reported some relationships between donepezil treatment and hippocampus in Alzheimer's disease (AD). However, due to methodological limitations, their close relationships remain unclear. The aim of this study is to predict treatment response to donepezil by utilizing the automated segmentation of hippocampal subfields volumes (ASHS) in AD. Sixty four AD patients were prescribed with donepezil and were followed up for 24 weeks. Cognitive function was measured to assess whether there was a response from the donepezil treatment. ASHS was implemented on non-responder (NR) and responder (TR) groups, and receiver operator characteristic (ROC) analysis was conducted to evaluate the sensitivity, specificity, and accuracy of hippocampal subfields in predicting response to donepezil. The left total hippocampus and the CA1 area of the NR were significantly smaller than those of the TR group. The ROC curve analysis showed the left CA1 volumes showed highest area under curve (AUC) of 0.85 with a sensitivity of 88.0%, a specificity of 74.0% in predicting treatment response to donepezil treatment. We expect that hippocampal subfields volume measurements that predict treatment responses to current AD drugs will enable more evidence-based, individualized prescription of medications that will lead to more favorable treatment outcomes.

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Defining Treatment Response to Donepezil in Alzheimer’s Disease

Cited by 26 publications

References 24 publications

Short and Long-term Effects of rTMS Treatment on Alzheimer's Disease at Different Stages: A Pilot Study

Short and Long-term Effects of rTMS Treatment on Alzheimer's Disease at Different Stages: A Pilot Study

Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch

Prediction of Treatment Response to Donepezil using Automated Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease

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