Rationale for combination therapy with galantamine and memantine in alzheimer’s disease: the efficacy of treatment of addition

2011 ◽  
Vol 26 (S2) ◽  
pp. 507-507
Author(s):  
J. Zarra
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Well Being ◽  
Disease Assessment ◽  
Clinical Aspects ◽  
Neurocognitive Disorder ◽  
Clinical Dementia Rating ◽  
Open Label ◽  
Behavioural Symptoms

ObjectiveThe efficacy, safety, and tolerability of nootropic cholinergic agent: GALANTAMINE (with a dual mechanism of action on the cholinergic a system) and moderate affinity NMDA- receptor antagonist: MEMANTINE, were assessed taking into account the profile of patients with neurocognitive disorder: Alzheimer's disease, from the clinical aspects and the different classifications.MethodsThe experience included 428 patients who were enrolled in a prospective, observational, multicenter, and open-label study to receive 16 mg/day of galantamine and 30 mg/day of memantine for 12 months of treatment of addition.ResultsThe therapeutic response was measured using the Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Alzheimer's Disease Assessment Scale (ADAS-GOG), Functional Activities Questionnaire(FAQ) the Clinical Global Impression Scale (CGI) and the UKU scale of adverse effectstaking into account the efficacy, safety and adverse events of the treatment.The final results of the study showed that galantamine with addition memantine improves cognition, behavioural symptoms, and the general well-being of patients with cognitive impairment: Alzheimer's disease. The incidence of adverse events was not significant and a very good profile of tolerability and safety was observed.ConclusionAt the conclusion of this session, the participant should be able to demonstrate with use the association memantine - galatamine in neurocognitive disorder: Alzheimer's disease, improve cognition, behavioural symptoms, and the general state recognized as neurocognitive disorder.

scholarly journals CORRELATION OF CSF- AND MRI-BIOMARKERS AND PROGRESSION OF COGNITIVE DECLINE IN AN OPEN LABEL MCI TRIAL

2018 ◽  
pp. 1-5
Author(s):  
L.K. Joachim ◽  
L. Frölich ◽  
E. Rüther ◽  
J. Wiltfang ◽  
W. Maier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Total Duration ◽  
Cognitive Testing ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Open Label ◽  
Amnestic Mci ◽  
Multicenter Rct

Background: In several randomized controlled trials (RCT) acetylcholinesterase-inhibitors (AChE-I) were tested in patients with mild cognitive impairment (MCI) but were ineffective in delaying disease progression as determined by neuropsychological testing only. Here we present data from an open label observational extension of a multicenter RCT in order to assess if biomarkers are providing useful additional information about a drug’s efficacy. We followed 83 amnestic MCI patients and performed correlational analyses of Aβ 1-42 and total-Tau in the cerebrospinal fluid (CSF), hippocampal and amygdala volume at baseline, the total duration of blinded and open label AChE-I treatment and the outcome 24 months after inclusion into the RCT. Twelve out of 83 amnestic MCI (14%) had progressed to Alzheimer’s disease (AD). Overall, worsening and disease progression as measured by the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog), Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating (CDR) did not correlate with the duration of AChE-I treatment. However, a specific multidimensional biomarker profile at baseline indicated more reliably than cognitive testing alone progression to AD. We conclude that pharmacological RCTs testing symptomatic treatment effects in MCI should include biomarker assessment.

scholarly journals Psychometric Properties of the Clinical Dementia Rating – Sum of Boxes and Other Cognitive and Functional Outcomes in a Prodromal Alzheimer’s Disease Population

2020 ◽  
pp. 1-10
Author(s):  
F. McDougall ◽  
C. Edgar ◽  
M. Mertes ◽  
P. Delmar ◽  
P. Fontoura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Psychometric Properties ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Prodromal Ad ◽  
Ceiling Effects ◽  
Prodromal Alzheimer’S Disease ◽  
Selective Reminding Test

BACKGROUND: The Clinical Dementia Rating–Sum of Boxes (CDR-SB) has been proposed as a primary outcome for use in prodromal AD trials. However, the psychometric properties of this, and of other commonly used measures, have not been well-established in this patient population. OBJECTIVE: To describe the psychometric properties of commonly used efficacy measures in a clinical trial of prodromal AD. SETTING: Data were gathered as part of a two-year clinical trial. PARTICIPANTS: Patients had biomarker confirmed prodromal AD. MEASUREMENTS: Clinical Dementia Rating (CDR), Functional Activities Questionnaire (FAQ), Alzheimer’s Disease Assessment Scale – Cognition Subscale 11 and 13 (ADAS-Cog), Mini Mental State Exam (MMSE), and Free and Cued Selective Reminding Test (FCSRT-IR [words]). Assessments were conducted at least every 24 weeks. RESULTS: For the CDR-SB, test-retest reliability was good (intra-class correlation coefficient [ICC]=0.83); internal consistency was 0.65 at baseline but above 0.8 at later assessments. Relationships between the CDR-SB and other measures were as expected (higher correlations with more closely related constructs), and the CDR-SB differentiated between patients with different severities of dementia (-2.9 points difference between CDR-Global Score 0.5 and 1, P<.0001). Floor and ceiling effects on the CDR-SB total score were minimal; however, at baseline there were ceiling effects in the personal care domain. Further detail is provided on the psychometric properties of ADAS-Cog, MMSE, FCSRT-IR and FAQ in this population. CONCLUSION: The psychometric properties of the CDR-SB are adequate in prodromal AD and continued use is warranted in clinical trials. However, there remains scope for improvement in the assessment of functional constructs and development of novel measures should continue.

scholarly journals Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline

Neurology ◽  
2017 ◽  
Vol 89 (21) ◽  
pp. 2176-2186 ◽  
Author(s):  
Shannon L. Risacher ◽  
Wesley H. Anderson ◽  
Arnaud Charil ◽  
Peter F. Castelluccio ◽  
Sergey Shcherbinin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Alzheimer Disease ◽  
Volume Ratio ◽  
Hippocampal Volume ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Categorical Models

Objective:To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline.Methods:Amyloid-positive participants with AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSpMRI], limbic predominant [LPMRI], typical AD [tADMRI]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models.Results:When participants were divided categorically, the HpSpMRI group showed significantly more AD-like hypometabolism on 18F-fluorodeoxyglucose-PET (p < 0.05) and poorer baseline executive function (p < 0.001). Other baseline clinical measures did not differ across the 3 groups. Participants with HpSpMRI also showed faster subsequent clinical decline than participants with LPMRI on the Alzheimer's Disease Assessment Scale, 13-Item Subscale (ADAS-Cog13), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all p < 0.05) and tADMRI on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both p < 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog13 score (p < 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy.Conclusions:AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation.

scholarly journals 183 AXONA (Caprylidene): Medical Food Therapy For Alzheimer’s Disease

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 105-105 ◽  
Author(s):  
Shanila Shagufta ◽  
Venkatesh Sreeram ◽  
Faisal Kagadkar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Risk ◽  
Cognitive Functioning ◽  
Treatment Options ◽  
Acetylcholinesterase Inhibitors ◽  
Normal Diet ◽  
Disease Assessment ◽  
High Risk Population ◽  
Open Label

OBJECTIVESEvaluate the current novel food therapy for Alzheimer and its adverse effects. What is the response to Axona (Capylidene) in different ethnicities and determine the generalizability of the drug use in diverse populations.What genes are linked with positive responses? What are the implications of its use in high risk populations? Its role in early detection of Alzheimer’s and the arrest of the neurodegeneration in APO E4 (-) patients.METHODPubMed was queried with the search terms ‘Axona’ OR ‘Caprylidene’ and the following articles were collected and reviewed.RESULTSAmong the articles collected and reviewed, two studies extensively evaluated the safety and efficacy of using Medium Chain Triglycerides (MCT) in Alzheimer’s disease. These studies genotyped patients for APO E4 status (positive/negative). According to the Reger et al. study in 2002, treatment of APOE4 (-ve) patients with MCTs reported a considerable improvement in comparison to placebo-treated patients (P=0.04). The second study by Henderson et al. in 2009 demonstrated an improvement in cognitive functioning determined by Alzheimer’s disease Assessment Scale- cognitive subscale (ADAS-Cog) scores in those treated with MCTs versus placebo in APOE4 -ve patients. An open label Japanese pilot study also showed improvement in cognitive functioning with Caprylidene in APOE4 (-ve) patients with Mini Mental Status Exam (MMSE) score>14.DISCUSSIONThe FDA approved treatment options in Alzheimer’s disease include acetylcholinesterase inhibitors (Rivastigmine, Donepezil and Galantamine), NMDA receptor antagonist (Memantine). These drugs only delay the progression of the disease in these patients.MCTs are classified as medical foods, which are defined as substances that provide a specific nutritional need in a patient that cannot be satisfied by modification of a normal diet alone The FDA approved Axona as medicalfood for specific dietary management of the disease in 2009. Early metabolic changes in Alzheimer’s Diseaseprior to cognitive decline and plaque deposition can possibly be prevented by early intervention with Axona, especially in high risk population (APOE4 (þ), Downs syndrome).These trials highlight the benefits of MCT in a discrete group, and the importance of routine genomic testing in Alzheimer patients in clinical settings. A better understanding into Caprylidene’s pharmacokinetics and pharmacodynamics will help us in the prevention and intervention of patients based on their genetic profiles.Funding AcknowledgementsNo funding.

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.

DETECTING TREATMENT GROUP DIFFERENCES IN ALZHEIMER’S DISEASE CLINICAL TRIALS: A COMPARISON OF ALZHEIMER’S DISEASE ASSESSMENT SCALE - COGNITIVE SUBSCALE (ADAS-COG) AND THE CLINICAL DEMENTIA RATING - SUM OF BOXES (CDR-SB)

2018 ◽  
pp. 1-6
Author(s):  
A.M. Wessels ◽  
S.A. Dowsett ◽  
J.R. Sims
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Treatment Group ◽  
Assessment Tool ◽  
Disease Assessment ◽  
Group Differences ◽  
Original Form ◽  
Clinical Dementia Rating ◽  
Cognitive Subscale

The Alzheimer’s Disease Assessment Scale’s cognitive subscale (ADAS-Cog) has been widely used as an outcome measure in Alzheimer’s Disease (AD) clinical trials. In its original form (ADAS-Cog11), the scale has been used successfully in mild-to-moderate AD dementia populations, but its use is more limited in the study of earlier disease (mild cognitive impairment [MCI] or mild dementia due to AD) owing to lack of appropriate sensitivity of some items. With recent focus on earlier treatment, efforts have focused on the development of more sensitive tools, including the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a global assessment tool to evaluate both cognition and function. The ability of the ADAS-Cog and CDR-SB to detect treatment group differences in the clinical trial environment has not been systematically studied. The aim of this analysis was to compare the utility of these tools in detecting treatment group differences, by reviewing study findings identified through advanced searches of clinicaltrials.gov and Ovid, and press releases and scientific presentations. Findings from placebo-controlled studies of ≥ 6m duration and enrolling >100 participants were included; reporting of both the ADAS-Cog and CDR-SB at endpoint was also a requirement. Of the >300 records identified, 34 studies fulfilled the criteria. There were significant placebo versus active drug group differences based on findings from at least one measure for 14 studies. The ADAS-Cog detected treatment differences more frequently than the CDR-SB. Based on these and previously published findings, the ADAS-Cog appears more useful than the CDR-SB in detecting treatment group differences.

scholarly journals Longitudinal Sensitivity of Alzheimer’s Disease Severity Staging

2020 ◽  
Vol 35 ◽  
pp. 153331752091871 ◽  
Author(s):  
Julia S. Benoit ◽  
Wenyaw Chan ◽  
Linda Piller ◽  
Rachelle Doody
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Decision Making ◽  
Disease Severity ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Disease Assessment ◽  
Progression Rate ◽  
Clinical Dementia Rating ◽  
Cognitive Subscale

Understanding Alzheimer’s disease (AD) dynamics is essential in diagnosis and measuring progression for clinical decision-making; however, clinical instruments are imperfect at classifying true disease stages. This research evaluates sensitivity and determinants of AD stage changes longitudinally using current classifications of “mild,” “moderate,” and “severe” AD, using Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog), and the Clinical Dementia Rating–Sum of Boxes (CDR-SB) thresholds. Age and pre-progression rate were significant determinants of AD progression using MMSE alone to stage AD, and pre-progression was found to impact disease progression with CDR-SB. Sensitivity of these instruments for identifying clinical stages of AD to correctly staging a “moderate” level of disease severity for outcomes MMSE, CDR-SB, and ADAS-Cog was 92%, 78%, and 92%, respectively. This research derives longitudinal sensitivity of clinical instruments used to stage AD useful for clinical decision-making. The MMSE and ADAS-Cog provided adequate sensitivity to classify AD stages.

scholarly journals Effects of Two-Year Treatment with the Cholinesterase Inhibitor Rivastigmine on Behavioural Symptoms in Alzheimer’s Disease

1999 ◽  
Vol 11 (4) ◽  
pp. 211-216 ◽  
Author(s):  
Michael Rösler ◽  
Wolfgang Retz ◽  
P. Retz-Junginger ◽  
Hans Joachim Dennler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitor ◽  
International Study ◽  
Term Treatment ◽  
Open Label ◽  
Behavioural Symptoms ◽  
Psychopathological Symptoms ◽  
Long Term Treatment

Alzheimer’s disease (AD) is accompanied by prominent behavioural disturbances. They cause significant distress for both caregivers and patients and can play a major role in the decision to institutionalise AD patients. Recent evidence suggests that cholinergic deficiencies not only contribute to the memory and cognitive abnormalities of AD but are also responsible for some behavioural abnormalities seen over the course of the disease. In this study we assessed the ability of rivastigmine, a pseudo-irreversible cholinesterase inhibitor, to improve behavioural and psychopathologic symptoms in AD. The analysis included 34 patients present in the Germanarm of the international study B303 who received and completed long-term treatment with rivastigmine in the open-label study B305. Assessments of behaviour and psychopathological symptoms were performed using the behavioural component of the Clinicians Interview Based Impression of Change Plus (CIBIC-Plus). Results show that long-term treatment with rivastigmine can slow the progression of behavioural and psychopathological symptoms of AD. Behavioural symptoms showing stabilisation included aggressiveness, activity disturbances, hallucinations and paranoid features. Results also suggest that patients treated earlier with rivastigmine may attain a greater benefit compared with patients whose treatment is delayed 6 months. Further studies examining the effects of rivastigmine on behavioural disturbances in AD are therefore warranted.

scholarly journals 432 – Correlation between regional brain volume and olfactory function in very mild amnestic patients

2020 ◽  
Vol 32 (S1) ◽  
pp. 148-148
Author(s):  
Tetsuo Kashibayashi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gray Matter Volume ◽  
Temporal Cortex ◽  
Word Recall ◽  
Disease Assessment ◽  
Parahippocampal Gyrus ◽  
Clinical Dementia Rating ◽  
Detection And Identification ◽  
Olfactory Detection

Background & Aims: We aimed to determine neural correlates of olfactory detection and identification and analyze associations between cognitive function and olfactory identification or detection in very mild amnestic patients.Methods: We recruited 70 patients with chief complaints of memory impairment diagnosed as amnestic mild cognitive impairment (MCI) or Alzheimer’s disease (AD) with a clinical dementia rating of 0.5. Olfactory detection and identification were assessed using T&T olfactometry. A voxel-wise correlation analysis of gray matter volume and olfactometry scores was performed. We also analyzed correlations between neuropsychological results and olfactometry scores.Results: A significant negative correlation was observed between detection scores and nucleus accumbens and left parahippocampal gyrus volumes and between identification scores and orbitofrontal, right frontal, and right anterior temporal cortex volumes (p<0.001). No significant correlation existed between detection and cognitive assessment scores. Identification score was significantly correlated with the Alzheimer’s Disease Assessment Scale-Cognitive Part word recall score (r=0.305, p=0.01).Conclusions: Olfactory detection and identification dysfunction were attributable to impairments in different regions in MCI and very early AD; the former was attributed to the olfactory circuit, while the latter to neocortices. The dysfunction of identification of olfactory information was associated with episodic memory in those patients.

Correlates of Dropout, Efficacy, and Adverse Events in Treatment With Acetylcholinesterase Inhibitors in Korean Patients With Alzheimer's Disease

2002 ◽  
Vol 14 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Jae-Min Kim ◽  
Il-Seon Shin ◽  
Jin-Sang Yoon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Clinical Characteristics ◽  
Financial Burden ◽  
Acetylcholinesterase Inhibitors ◽  
Psychological State ◽  
Clinical Dementia Rating ◽  
Korean Patients ◽  
Assessment Scales

The correlates of dropout, efficacy, and adverse events in the tratment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (ChEI) are unclear. To investigate these issues, a 26-week prospective, randomized, open-labeled trail with donepezil or rivastigmine was undertaken. Sixty-four Korean patients with AD were recruited, and data on sociodemographic and clinical characteristics and several assessment scales were collected. Characteristics of available caregivers were also gathered. Information on adverse events and dropout was recorded. Thirty-five (55%) patients dropped out during treatment with ChEI, for reasons mainly related to financial burden of caregivers. Of the 29 patients who completed the 26-week trial, 16 (55%) were responsive to ChEI. Lower scores on the Clinical Dementia Rating and Blessed Dementia Scale at baseline were associated with the efficacy of ChEI. Of the total participants, 26 (41%) experienced adverse events, although these seemed to be mild and appeared to be associated with the psychological state of patients or coadministration of psychotropic drugs. In conclusion, ChEI seemed to be effective and well tolerated in the treatment of Korean patients with AD, but the use of this drug was limited mainly by the financial burden of caregivers.

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