Attenuation in the Progression of Cognitive Deterioration in Alzheimer's Disease With Rivastigmine: A Dose-Dependent Effect

CNS Spectrums ◽  
2000 ◽  
Vol 5 (6) ◽  
pp. 21-22 ◽  
Author(s):  
Martin Farlow ◽  
John Messina ◽  
Ravi Anand ◽  
Richard Hartman ◽  
Jeffrey Veach
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Controlled Trial ◽  
Weighted Least Squares ◽  
Disease Assessment ◽  
Cognitive Deterioration ◽  
Attrition Rates ◽  
Cognitive Subscale ◽  
Rate Of Decline

AbstractObjectives: Possible disease-modifying effects of rivastigmine have been suggested by analyses using a variation of the randomized start design; however, the results were somewhat confounded by differing attrition rates. We report on an alternative method investigating whether increasing doses reduce the rates of cognitive decline in patients who continue treatment.Methods: The effect of dose on the rate of cognitive decline seen on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was explored for patients in a long-term (130-week) extension of a 26-week placebo-controlled trial using two methods: a weighted leas squares regression analysis using each individual's slope, and a weighted analysis of variance (ANOVA) comparing the slopes of patients categorized by dose (≤6 mg/d or >6 mg/d).Results: The results from 408 patients included in the weighted least squares analysis estimated the rate of decline to attenuate by approximately 1 point/y for every 3 mg/d increase (P<.0001). The average annual rate of decline for patients whose mean dose was >6 mg/d was 4.5 points (95% Cl, 5.1–3.9), while for patients with a mean dose of≥6 mg/d a decline of 8.2 points (95% Cl, 9.1–7.3) was seen.Conclusion: These data further support earlier results suggesting that rivastigmine reduces the rate of progression of cognitive deterioration in Alzheimer's disease.

scholarly journals A Randomized, Controlled Trial of Linopirdine in the Treatment of Alzheimer's Disease

1997 ◽  
Vol 24 (2) ◽  
pp. 140-145 ◽  
Author(s):  
Kenneth Rockwood ◽  
B. Lynn Beattie ◽  
M. Robin Eastwood ◽  
Howard Feldman ◽  
Erich Mohr ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Controlled Trial ◽  
Small Degree ◽  
Disease Assessment ◽  
Double Blind ◽  
Cognitive Subscale ◽  
Parallel Group ◽  
Treatment Dose ◽  
Age Range

ABSTRACT:Objectives:We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease.Methods:A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline.Results:No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01.Conclusions:This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

scholarly journals Benfotiamine and Cognitive Decline in Alzheimer’s Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial

2020 ◽  
Vol 78 (3) ◽  
pp. 989-1010
Author(s):  
Gary E. Gibson ◽  
José A. Luchsinger ◽  
Rosanna Cirio ◽  
Huanlian Chen ◽  
Jessica Franchino-Elder ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Placebo Group ◽  
Cognitive Decline ◽  
Controlled Trial ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Positron Emission

Background: In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer’s disease (AD) including impaired cognition, amyloid-β plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation. Objective: To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine. Methods: A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome. Results: Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125). Worsening in CDR was 77% lower (p = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOE ɛ4 non-carriers. Benfotiamine significantly reduced increases in AGE (p = 0.044), and this effect was stronger in the APOE ɛ4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p = 0.002). Conclusion: Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.

scholarly journals Effectiveness and Safety of MLC601 in the Treatment of Mild to Moderate Alzheimer's Disease: A Multicenter, Randomized Controlled Trial

2015 ◽  
Vol 5 (1) ◽  
pp. 96-106 ◽  
Author(s):  
Hossein Pakdaman ◽  
Ali Amini Harandi ◽  
Hamidreza Hatamian ◽  
Mojgan Tabatabae ◽  
Hosein Delavar Kasmaei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Diagnostic Interview ◽  
Disease Assessment ◽  
Amyloid Precursor Protein Processing ◽  
Randomized Controlled ◽  
Cognitive Subscale ◽  
Multicenter Randomized Controlled Trial

Background: MLC601 is a possible modulator of amyloid precursor protein processing, and in a clinical trial study MLC601 showed some effectiveness in cognitive function in Alzheimer's disease (AD) patients. We aimed to evaluate the effectiveness and safety of MLC601 in the treatment of mild to moderate AD as compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine and galantamine. Methods: In a multicenter, nonblinded, randomized controlled trial, 264 volunteers with AD were randomly divided into 4 groups of 66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and galantamine, respectively. Subjects underwent a clinical diagnostic interview and a cognitive/functional battery including the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog). Patients were visited every 4 months, and the score of cognition was recorded by the neurologists. Results: There were no significant differences in age, sex, marital status and baseline score of cognition among the 4 groups. In total, 39 patients (14.7%) left the study. Trend of cognition changes based on the modifications over the time for MMSE and ADAS-cog scores did not differ significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog). Conclusion: MLC601 showed a promising safety profile and also efficacy compared to 3 FDA-approved ChEIs.

scholarly journals Genetic variants beyond amyloid and tau associated with cognitive decline

Neurology ◽  
2020 ◽  
Vol 95 (17) ◽  
pp. e2366-e2377 ◽  
Author(s):  
Hang-Rai Kim ◽  
Taeyeop Lee ◽  
Jung Kyoon Choi ◽  
Yong Jeong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Structural Equation ◽  
Equation Model ◽  
Disease Assessment ◽  
Glutathione Metabolism ◽  
Nucleotide Polymorphisms ◽  
Cognitive Subscale

ObjectiveTo identify single nucleotide polymorphisms (SNPs) associated with cognitive decline independent of β-amyloid (Aβ) and tau pathology in Alzheimer disease (AD).MethodsDiscovery and replication datasets consisting of 414 individuals (94 cognitively normal control [CN], 185 with mild cognitive impairment [MCI], and 135 with AD) and 72 individuals (22 CN, 39 with MCI, and 11 with AD), respectively, were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Genome-wide association analysis was conducted to identify SNPs associated with individual cognitive function (measured with the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale–Cognitive Subscale ) while controlling for the level of Aβ and tau (measured as CSF phosphorylated-tau/Aβ1-42). Gene ontology analysis was performed on SNP-associated genes.ResultsWe identified 1 significant (rs55906536, β = −1.91, standard error 0.34, p = 4.07 × 10−8) and 4 suggestive variants on chromosome 6 that were associated with poorer cognitive function. Congruent results were found in the replication data. A structural equation model showed that the identified SNP deteriorated cognitive function partially through cortical thinning of the brain in a region-specific manner. Furthermore, a bioinformatics analysis showed that the identified SNPs were associated with genes related to glutathione metabolism.ConclusionsIn this study, we identified SNPs related to cognitive decline in a manner that could not be explained by Aβ and tau levels. Our findings provide insight into the complexity of AD pathogenesis and support the growing literature on the role of glutathione in AD.

scholarly journals Orthostatic Blood Pressure Recovery Is Associated With the Rate of Cognitive Decline and Mortality in Clinical Alzheimer’s Disease

2020 ◽  
Vol 75 (11) ◽  
pp. 2169-2176
Author(s):  
Rianne A A de Heus ◽  
Daan L K de Jong ◽  
Anne Rijpma ◽  
Brian A Lawlor ◽  
Marcel G M Olde Rikkert ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Confidence Interval ◽  
Cognitive Decline ◽  
Controlled Trial ◽  
Intervention Group ◽  
Disease Assessment ◽  
Progression Rate ◽  
Initial Drop

Abstract Background Impaired recovery of blood pressure (BP) after standing has been shown to be related to cognitive function and mortality in people without dementia, but its role in people with Alzheimer’s disease (AD) is unknown. The aim of this study was to investigate the association of the orthostatic BP response with cognitive decline and mortality in AD. Methods In this post hoc analysis of a randomized controlled trial (Nilvad), we measured the beat-to-beat response of BP upon active standing in mild-to-moderate AD. This included the initial drop (nadir within 40 seconds) and recovery after 1 minute, both expressed relative to resting values. We examined the relationship between a small or large initial drop (median split) and unimpaired (≥100%) or impaired recovery (&lt;100%) with 1.5-year change in Alzheimer’s Disease Assessment—cognitive subscale (ADAS-cog) scores and all-cause mortality. Results We included 55 participants (age 73.1 ± 6.2 years). Impaired BP recovery was associated with higher increases in ADAS-cog scores (systolic: β [95% confidence interval] = 5.6 [0.4–10.8], p = .035; diastolic: 7.6 [2.3–13.0], p = .006). During a median follow-up time of 49 months, 20 participants died. Impaired BP recovery was associated with increased mortality (systolic: HR [95% confidence interval] = 2.9 [1.1–7.8], p = .039; diastolic: HR [95% confidence interval] = 5.5 [1.9–16.1], p = .002). The initial BP drop was not associated with any outcome. Results were adjusted for age, sex, and intervention group. Conclusions Failure to fully recover BP after 1 minute of standing is associated with cognitive decline and mortality in AD. As such, BP recovery can be regarded as an easily obtained marker of progression rate of AD.

Validation of the Hungarian version of Alzheimer’s Disease Assessment Scale – Cognitive Subscale

2012 ◽  
Vol 153 (12) ◽  
pp. 461-466 ◽  
Author(s):  
Magdolna Pákáski ◽  
Gergely Drótos ◽  
Zoltán Janka ◽  
János Kálmán
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mental State ◽  
Mini Mental State Examination ◽  
Assessment Scale ◽  
Disease Assessment ◽  
Control Subjects ◽  
Cognitive Subscale ◽  
State Examination ◽  
Hungarian Version

The cognitive subscale of the Alzheimer’s Disease Assessment Scale is the most widely used test in the diagnostic and research work of Alzheimer’s disease. Aims: The aim of this study was to validate and investigate reliability of the Hungarian version of the Alzheimer’s Disease Assessment Scale in patients with Alzheimer’s disease and healthy control subjects. Methods: syxty-six patients with mild and moderate Alzheimer’s disease and 47 non-demented control subjects were recruited for the study. The cognitive status was established by the Hungarian version of the Alzheimer’s Disease Assessment Scale and Mini Mental State Examination. Discriminative validity, the relation between age and education and Alzheimer’s Disease Assessment Scale, and the sensitivity and specificity of the test were determined. Results: Both the Mini Mental State Examination and the Alzheimer’s Disease Assessment Scale had significant potential in differentiating between patients with mild and moderate stages of Alzheimer’s disease and control subjects. A very strong negative correlation was established between the scores of the Mini Mental State Examination and the Alzheimer’s Disease Assessment Scale in the Alzheimer’s disease group. The Alzheimer’s Disease Assessment Scale showed slightly negative relationship between education and cognitive performance, whereas a positive correlation between age and Alzheimer’s Disease Assessment Scale scores was detected only in the control group. According to the analysis of the ROC curve, the values of sensitivity and specificity of the Alzheimer’s Disease Assessment Scale were high. Conclusions: The Hungarian version of the Alzheimer’s Disease Assessment Scale was found to be highly reliable and valid and, therefore, the application of this scale can be recommended for the establishment of the clinical stage and follow-up of patients with Alzheimer’s disease. However, the current Hungarian version of the Alzheimer’s Disease Assessment Scale is not sufficient; the list of words and linguistic elements should be selected according to the Hungarian standard in the future. Orv. Hetil., 2012, 153, 461–466.

scholarly journals Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soo Hyun Cho ◽  
Sookyoung Woo ◽  
Changsoo Kim ◽  
Hee Jin Kim ◽  
Hyemin Jang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Assessment ◽  
Time Interval ◽  
Disease Course ◽  
Preclinical Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
Preclinical Ad ◽  
Cognitive Subscale

AbstractTo characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

Influence of Educational Attainment on Cognition-Based Intervention Programs for Persons with Mild Alzheimer’s Disease

2016 ◽  
Vol 22 (5) ◽  
pp. 577-582 ◽  
Author(s):  
Israel Contador ◽  
Bernardino Fernández-Calvo ◽  
Francisco Ramos ◽  
Javier Olazarán
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Effect Size ◽  
Study Groups ◽  
Total Sample ◽  
Cognitive Intervention ◽  
Potential Effect ◽  
Cognitive Status ◽  
Disease Assessment

AbstractObjectives: This research retrospectively analyzed the effect of education on cognitive interventions carried out in patients with mild Alzheimer’s disease (AD). Methods: The total sample consisted of 75 patients with mild AD receiving treatment with cholinesterase inhibitors. The participants were divided into two groups: cognitive intervention (IG; n=45) and waiting list (WLG; n=30). Patients in the IG received either the Big Brain Academy (n=15) or the Integrated Psychostimulation Program (n=30) during 12 weeks. The influence of education on intervention effect was analyzed comparing mean change scores of the two study groups in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), stratified by educational level. The potential effect of age, sex, cognitive status, and type of intervention was examined using post hoc stratification analyses. Results: Higher education was associated with faster cognitive decline in the WLG (effect size=0.51; p<.01). However, cognitive evolution was not influenced by education in the IG (effect size=0.12; p=.42). Conclusions: Our results suggest that cognitive intervention might delay accelerated cognitive decline in higher educated individuals with mild AD. (JINS, 2016, 23, 1–6)

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