Efficacy, Safety and tolerability of the once-daily 10 cm² rivastigmine patch formulation in the patients with dementia (with probable Alzheimer’s disease)

Back ground: Treatment compliance in patients with Alzheimer’s disease is particularly important as patients receiving regular treatment have a greater chance of slowing or delaying disease progression. Transdermal delivery has the potential for providing continuous drug delivery and steady plasma levels. Current study aimed to evaluate safety and tolerability of rivastigmine patch, to assess patient compliance and to assess the efficacy of treatment in patients with dementia (with probable Alzheimer’s disease). Methods: A total of 112 dementia patients (with a diagnosis of probable Alzheimer’s disease) from 12 centers were enrolled who were residing with someone in the communities throughout the study. After eligibility, and baseline assessments, patients were entered a 24-week open label treatment phase. All patients were started with application of one 5 cm² patch, followed by an up-titration to the target dose of 10 cm² patch size. Efficacy assessments were performed at weeks 12 and 24 in terms of MMSE and GDS score. Safety was monitored at all assessment points based mainly on the frequency of adverse events. Results: Analysis of baseline and available data until the drop out revealed no significant differentials. Around 95% of the study participants could receive 10 cm² patch size, showing a very high tolerability of the patch. Concurrent medication use also showed significant reduction to 16.3% patient in the end from 25% at baseline. The average MMSE score increased to 19.3 (±3.1) at 12th week and to 20.6(±3.4) at 24th week from 16.8 (±3.2) at baseline. GDS score reduced to 3.7 (±1.4) at 12th week and to 3.2 (±1.3) at 24th week from 4.3 (±1.5) at baseline. Only eight occasions of adverse event was reported (8.2%); no serious adverse event (SAE) were reported. Lost to follow up in the study was 14 (12.5%). Analysis of baseline data shows no significant difference. Their withdrawal seems to be unrelated to the adverse events and treatment outcome. Among the lost to follow up only one 1 (7.1%) had some side effect. Conclusion: Our study supports the pharmacokinetic rationale for the rivastigmine patch, indicating that smooth and continuous delivery of rivastigmine translates into an improved tolerability profile versus conventional oral administration, while maintaining clinical effectiveness. Bangladesh Journal of Neuroscience 2013; Vol. 29 (1) : 5-14

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The Gospel Oak Study stage II: the diagnosis of dementia in the community

Psychological Medicine ◽

10.1017/s0033291700036588 ◽

1990 ◽

Vol 20 (4) ◽

pp. 881-891 ◽

Cited By ~ 28

Author(s):

Gill Livingston ◽

Karen Sax ◽

Jo Willison ◽

Bob Blizard ◽

Anthony Mann

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Investigation ◽

Community Sample ◽

Syndrome Scale ◽

Diagnosis Of Dementia ◽

Organic Brain ◽

Lost To Follow Up ◽

Reversible Condition

SynopsisAn attempt was made to assess in detail subjects screened as suffering from dementia among a North London community sample of elderly people. Forty-eight (80 %) subjects were interviewed, 7 (12%) were found to have died and 5 (8%) either refused interview or were lost to follow-up. By clinicians' diagnosis of the 48 interviewed, 22 subjects (46%) had probable Alzheimer's disease, one had multi-infarct dementia, five had mixed dementia, five had secondary dementia, 10 had a dementia which could not be further classified and 5 were not demented. No subject had a reversible condition. The prevalence rate for clinical dementia was 6·1 %, and for Alzheimer's disease 3·1 %. According to AGECAT diagnosis the prevalence of organicity was 5·7%. The AGECAT diagnoses and psychiatrists' diagnoses were significantly associated (P < 0·003) and AGECAT was more likely to identify as organic those subjects with dementia diagnosed by psychiatrists as Alzheimer's disease, than those not so diagnosed (P < 0·04). A short psychometric battery, including the MMSE in two versions, was administered and its acceptability to a community sample evaluated. This detailed clinical investigation showed that the Dementia Diagnostic Scale of the Short-CARE was a specific predictor of clinical dementia or death at the time of follow-up, whereas the more inclusive Organic Brain Syndrome scale was a more satisfactory first phase screening instrument.

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The Alzheimer’s Disease THErapy with NEuroaid II (ATHENE) Study: A Double-Blind Randomized Delayed-Start Trial to Assess the Safety and Efficacy of MLC901 (NeuroAiD™II) as an add-on Treatment to Cholinesterase Inhibitors or Memantine in Patients With Mild to Moderate Alzheimer's Disease

10.21203/rs.3.rs-494674/v1 ◽

2021 ◽

Author(s):

Christopher Chen ◽

Qingshu Liu ◽

Rejesh Babu Moorakonda ◽

Nagaendran Kandiah ◽

Boon Yeow Tan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Adverse Events ◽

Cognitive Assessment ◽

Standard Treatment ◽

Serious Adverse Events ◽

Significant Difference ◽

Early Starters ◽

Modifying Effect ◽

Disease Modifying

Abstract BackgroundPreclinical and clinical studies indicate a role for MLC901 (NeuroAiDTMII) in Alzheimer’s Disease (AD). We investigated its safety and efficacy as add-on therapy to standard treatment and evaluated a disease modifying effect in mild to moderate AD.MethodsMild-moderate probable AD patients by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n=125) were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months during which all patients received MLC901, in a delayed-start design. The primary outcome measure was serious adverse events at 6 months, secondary outcomes included the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) and other cognitive assessment scales.ResultsThere was no significant difference in the risk of serious adverse events between early and delayed starters at month (M) 6 (22.6% vs. 27.0%, risk difference = -4.4%, 90% CI -16.9 to 8.3%). Furthermore, there was no significant difference in the risk of adverse events, including the occurrence of stroke or vascular events, between early and delayed starters throughout the 12-month study period. The early-starters differed significantly on ADAS-Cog from the delayed-starters at M9 (mean difference -3.36, 95% CI -5.64 to -1.09) and M12 (mean difference -2.35, 95% CI -5.45 to 0.74). Other cognitive assessment scales showed trends in favor of MLC901.ConclusionsMLC901 is a safe adjunct to standard treatment for mild-moderate AD. There is no indication that the risk of any adverse events, including vascular, is increased with MLC901 in the study population. The cognitive outcomes provide support for a disease-modifying effect of MLC901 which requires confirmation in further studies. Clinical trial registration: ClinicalTrials.gov, NCT03038035. https://clinicaltrials.gov/ct2/show/NCT03038035

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Phase II (NAVIGATE-AD study) Results of LY3202626 Effects on Patients with Mild Alzheimer’s Disease Dementia

Journal of Alzheimer s Disease Reports ◽

10.3233/adr-210296 ◽

2021 ◽

pp. 1-16

Author(s):

Albert C. Lo ◽

Cynthia Duggan Evans ◽

Michele Mancini ◽

Hong Wang ◽

Sergey Shcherbinin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Adverse Events ◽

Functional Decline ◽

Neurofibrillary Tangle ◽

Amyloid Β ◽

System Organ Class ◽

Serious Adverse Events ◽

Study Results ◽

Significant Difference

Background: LY3202626 is a small molecule inhibitor of β-site amyloid precursor protein cleaving enzyme (BACE)1 shown to reduce amyloid-β (Aβ)1–40 and Aβ1–42 concentrations in plasma and cerebrospinal fluid developed for the treatment of Alzheimer’s disease (AD). Objective: To assess the change from baseline in flortaucipir positron emission tomography (PET) after treatment with LY3202626 compared with placebo in patients with mild. Methods: Patients received daily 3 mg or 12 mg doses of LY3202626 or placebo for 52 weeks. The primary outcome was assessment of cerebral neurofibrillary tangle load by flortaucipir PET. The study was terminated early following an interim analysis due to a low probability of identifying a statistically significant slowing of cognitive and/or functional decline. Results: A total of 316 patients were randomized and 47 completed the study. There was no statistically significant difference between placebo and either dose of LY3202626 from baseline to 52 weeks, or in annualized change for flortaucipir PET. There was no clinically meaningful difference between placebo and LY3202626 doses on efficacy measures of cognition and function. No deaths or serious adverse events considered related to LY3202626 were reported. A statistically significant increase in treatment-emergent adverse events in the psychiatric disorders system organ class was reported for both LY3202626 doses compared to placebo. Conclusion: LY3202626 tested at doses generating 70–90% BACE inhibition was generally well tolerated in this study. LY3202626 treatment did not result in a clinically significant change in cerebral tau burden as measured by flortaucipir nor in change of functional or cognitive decline compared to placebo.

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Factors Associated with Lumbar Puncture Participation in Alzheimer’s Disease Research

Journal of Alzheimer s Disease ◽

10.3233/jad-200394 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1559-1567

Author(s):

Madeleine M. Blazel ◽

Karen K. Lazar ◽

Carol A. Van Hulle ◽

Yue Ma ◽

Aleshia Cole ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Adverse Events ◽

Important Predictor ◽

Parental History ◽

Factors Associated ◽

Disease Research ◽

Relationship Of ◽

The Relationship

Background: Cerebrospinal fluid (CSF) provides insight into the spectrum of Alzheimer’s disease (AD) pathology. While lumbar punctures (LPs) for CSF collection are generally considered safe procedures, many participants remain hesitant to participate in research involving LPs. Objective: To explore factors associated with participant willingness to undergo a research LP at baseline and follow-up research study visit. Methods: We analyzed data from 700 participants with varying cognition (unimpaired, mild cognitive impairment, and dementia) in the Wisconsin Alzheimer’s Disease Research Center. We evaluated the relationship of demographic variables (age, sex, race, ethnicity, and years of education) and clinical variables (waist-to-hip ratio, body mass index, AD parental history, cognitive diagnosis) on decision to undergo baseline LP1. We evaluated the relationship of prior LP1 experience (procedure success and adverse events) with the decision to undergo follow-up LP2. The strongest predictors were incorporated into regression models. Results: Over half of eligible participants opted into both baseline and follow-up LP. Participants who underwent LP1 had higher mean education than those who declined (p = 0.020). White participants were more likely to choose to undergo LP1 (p < 0.001); 33% of African American participants opted in compared to 65% of white participants. Controlling for age, education, and AD parental history, race was the only significant predictor for LP1 participation. Controlling for LP1 mild adverse events, successful LP1 predicted LP2 participation. Conclusion: Race was the most important predictor of baseline LP participation, and successful prior LP was the most important predictor of follow-up LP participation.

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Safety Comparison of Two Enterovirus 71 (EV71) Inactivated Vaccines in Yiwu, China

Journal of Tropical Pediatrics ◽

10.1093/tropej/fmz004 ◽

2019 ◽

Vol 65 (6) ◽

pp. 547-551 ◽

Cited By ~ 1

Author(s):

Shuying Luo ◽

Fei Wu ◽

Xiaojun Ye ◽

Tao Fu ◽

Jingbo Tao ◽

...

Keyword(s):

Adverse Event ◽

Informed Consent ◽

Adverse Events ◽

Enterovirus 71 ◽

Dose Schedule ◽

Significant Difference ◽

Post Marketing ◽

Inactivated Vaccines ◽

Written Informed Consent

Abstract The safety of two kinds of post-marketing enterovirus 71 (EV71) vaccine in China was evaluated in this study. Fourteen vaccination clinics were randomly assigned in a 1:1 ratio, and both children in two groups were administered according to a two-dose schedule (on a 0 and 28 day schedule). Written informed consent was obtained, and recipients in this study were observed for 30 min after inoculation in the clinic, and then followed via phone or on-site follow-up at day 3 and 30. No severe EV71-associated adverse event was reported. No significant difference was noticed between Group Sinovac and Group CAMS (χz = 0.346, p = 0.556). There was no significant difference in the occurrence of adverse events among recipients aged less than 24 months; however, the proportion of adverse events was higher in Group CAMS than in Group Sinovac among the subjects aged 24–35 months (5.3% vs. 2.5%, p < 0.001). The two kinds of EV71 vaccines showed satisfactory safety. Adverse events after vaccination were normal and acceptable.

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P3-413: Eighteen-month follow-up data from the Canadian EMBRACE registry with the rivastigmine patch in patients with Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.2087 ◽

2012 ◽

Vol 8 (4S_Part_16) ◽

pp. P600-P600

Author(s):

Serge Gauthier ◽

Sandra Black ◽

Sharon Cohen ◽

Robillard Allain ◽

Martine Hubert ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Rivastigmine Patch

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Semantic Memory as an Early Cognitive Marker of Alzheimer’s Disease: Role of Category and Phonological Verbal Fluency Tasks

Journal of Alzheimer s Disease ◽

10.3233/jad-201452 ◽

2021 ◽

pp. 1-9

Author(s):

Camillo Marra ◽

Chiara Piccininni ◽

Giovanna Masone Iacobucci ◽

Alessia Caprara ◽

Guido Gainotti ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Semantic Memory ◽

Verbal Fluency ◽

Early Stage ◽

Significant Difference ◽

Wilks Lambda ◽

Marginal Means ◽

Post Hoc

Background: The assessment of semantic memory may be a useful marker to identify individuals with mild cognitive impairment (MCI) who will progress to Alzheimer’s disease (AD) in the early stages of the disease. Objective: The aim of this five-year follow-up longitudinal study is to assess whether semantic assessment could predict progression in MCI. Methods: A population of MCI (N = 251); mild (N = 178) and moderate AD (N = 114); and a sample of healthy participants (HP; N = 262) was investigated. The five-year follow-up of the MCI group was completed by 178 patients. Semantic and episodic memory measures were used, including a measure of the discrepancy between categorical and phonological verbal fluency, the semantic–phonological delta (SPD). The main outcome was the progression of MCI due to AD to dementia. Results: A general linear model showed a significant effect of diagnosis on SPD (Wilks’ Lambda = 0.591; p < 0.001). The estimated marginal means were –0.91 (SE = 0.185) in HP, –1.83 (SE = 0.187) in MCI, –1.16 (SE = 0.218) in mild AD, and –1.02 (SE = 0.275) in moderate AD. Post-hoc comparisons showed a significant difference between MCI and HP (p < 0.001). The follow-up was completed by 178 MCI individuals. SPD in MCI patients who progress to dementia was significantly lower than in MCI that will not progress (p = 0.003). Together with the Mini-Mental State Examination, the SPD was the only measure with a significant predicting effect at the five-years follow-up (p = 0.016). Conclusion: The SPD indicate the impairment of semantic memory in individuals with underlying AD at the MCI early stage, reflecting the early involvement of perirhinal and entorhinal cortices in the earliest stages of AD neuropathological process.

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Impact of depressive symptoms on outcome of Alzheimer's disease

Dementia & Neuropsychologia ◽

10.1590/s1980-57642010dn40400015 ◽

2010 ◽

Vol 4 (4) ◽

pp. 346-352 ◽

Cited By ~ 1

Author(s):

Anita de Paula Eduardo Garavello ◽

Regina Miksian Magaldi ◽

Sérgio Márcio Pacheco Paschoal ◽

Wilson Jacob Filho

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Depressive Symptoms ◽

The Elderly ◽

Functional Evaluation ◽

Depression Group ◽

Significant Difference ◽

The Impact ◽

Group D

Abstract There is no consensus in the medical literature about the impact of depressive symptoms on the evolution of Alzheimer's disease (AD). Objective: To compare the evolution of AD patients, with and without depressive symptoms, in terms of cognition, functionality and caregiver stress. Methods: The study entailed 2 stages: an initial retrospective stage involving review of medical charts of patients with mild and moderate AD. Patients were divided according to the presence or absence of depressive symptoms, defined by medical interview and questions on depressed mood from the CAMDEX (Cambridge Examination for Mental Disorders of the Elderly) and Neuropsychiatric Inventory (NPI). Twenty-nine patients were evaluated, 37.9% with depression (Group D+) and 62.1% without depression (Group D-). The groups were compared regarding demographic and medical characteristics, cognitive and functional performance, presence of apathy as a separate symptom, and caregiver stress, using standardized tests and questionnaires. In the second transversal step, the same tools were reapplied after 2 to 4 years of follow-up, and evolution for the two groups was compared. Results: The two groups were highly homogeneous in demographic and clinic characteristics, as well as in length of follow-up, and presented no significant difference in cognitive or functional evaluation at the time of diagnoses or after follow-up. Only caregiver stress was greater in Group D+ at the two time points (p<0.001). Conclusions: No differences in the evolution of AD patients with or without depressive symptoms were evident. Nevertheless, these symptoms were associated to emotional burden of caregivers.

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Clinical study on decreasing occurance of Alzheimer's Disease through intervention on amnestic Mild Cognitive Impairment with Di-Huang-Yi-Zhi formula in Shigatse, Tibet

10.21203/rs.3.rs-80949/v1 ◽

2020 ◽

Author(s):

Liming Zhang ◽

Ting Shen ◽

Hongmei An ◽

Canxing Yuan ◽

Jianwen Yan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Conversion Rate ◽

Amnestic Mild Cognitive Impairment ◽

Tibet Plateau ◽

Significant Difference ◽

One Year

Abstract Background Mild cognitive impairment (MCI) is generally considered a transitional stage between normal aging and AD dementia. This study aimed to analyze the efficacy of Di-Huang-Yi-Zhi (DHYZ) formula in treating amnestic Mild Cognitive Impairment (aMCI) for the patients in high altitude area (Qinghai Tibet Plateau). Method: A total of 106 patients in Shigatse, Tibet were randomly allocated into two groups. One group were to receive DHYZ decoction (150 ml each time, twice a day), the other group were to have aniracetam capsule (200 mg each time, three times a day) ,with 53 patients in each group. Changes in neuropsychological scales including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Barthel Index for activities of daily living (ADL) and TCM symptoms were detected during a 12-month treatment period. After one year follow-up, the conversion rate of AD was observed. Result There was no significant difference between the two groups in baseline characteristics and scale scores (P > 0.05). Compared with the aniracetam group, the DHYZ group showed statistically higher MMSE and MoCA score and lower TCM score at the 9-month and 12-month. In addition, the ADAS-Cog and ADL scores in DHYZ group at 12-month were lower than that in the aniracetam control group. After one year follow-up, the conversion rate of AD in DHYZ group was 10% (5/50), and aniracetam group was 15.69% (8/51). The conversion rate of AD in DHYZ group was significantly lower than that in aniracetam group. Conclusion DHYZ formula can improve the cognition behavior and global function of patients with aMCI, it can also delay the conversion to AD. This is represents a new treatment option for the patients.

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Sleep profile predicts the cognitive decline of mild-moderate Alzheimer’s disease patients

SLEEP ◽

10.1093/sleep/zsab117 ◽

2021 ◽

Author(s):

Adriano D S Targa ◽

Iván D Benítez ◽

Faridé Dakterzada ◽

Anna Carnes ◽

Montse Pujol ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cognitive Function ◽

Cognitive Decline ◽

Sleep Stage ◽

P Value ◽

Significant Difference ◽

Neuropsychological Evaluations

Abstract Study Objectives To investigate the association between sleep and cognitive decline of patients with mild-moderate Alzheimer’s disease. Methods Observational, prospective study, including consecutive patients diagnosed with mild-moderate Alzheimer’s disease. Cerebrospinal fluid was collected for amyloid-beta, total-tau, and phospho-tau levels determination. Also, overnight polysomnography was performed, followed by neuropsychological evaluations at baseline and after 12 months of follow-up. Principal component analysis revealed two profiles of patients in terms of sleep: one with a propensity to deepen the sleep (deep sleepers) and the other with a propensity to spend most of the time in the lighter sleep stage (light sleepers). Results The cohort included 125 patients with a median [IQR] of 75.0 [72.0;80.0] years. Deep and light sleepers did not present differences in relation to the cerebrospinal fluid pathological markers and to the cognitive function at the baseline. However, there was a significant difference of -1.51 (95% CI: -2.43 to -0.59) in the Mini-mental state examination after 12 months of follow-up. Accordingly, sleep depth and cognitive decline presented a dose-response relationship (p-for-trend = 0.02). Similar outcomes were observed in relation to the processing speed (Stroop words test, p-value = 0.016) and to the executive function (Verbal fluency test, p-value = 0.023). Conclusions Considering the increased cognitive decline presented by light sleepers, the sleep profile may have a predictive role in relation to the cognitive function of patients with mild-moderate Alzheimer’s disease. The modifiable nature of sleep sets this behavior as a possible useful intervention to prevent a marked cognitive decline.

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