Frank Tennigkeit

Treatment effects of Memantine on language in moderate to severe Alzheimer's disease patients.

Language impairment is one of the most troublesome manifestations of Alzheimers disease (AD). The objective of this post hoc analysis was to assess the treatment effects of Memantine on language in patients with moderate to severe AD, using the recently developed Severe Impairment Battery‐Language (SIB‐L) scale.

Sustained effects of once-daily memantine treatment on cognition and functional communication skills in patients with moderate to severe Alzheimer's disease: results of a 16-week open-label trial.

The present study evaluated the effects of once-daily memantine (20 mg) treatment on cognition and communication in patients with moderate to severe Alzheimers disease (AD). In a multicenter, single-arm open-label study, outpatients diagnosed with AD (MMSE < 20; n = 97) were titrated from 5 mg to 20 mg once-daily memantine over 4 weeks. Once-daily memantine treatment (20 mg) was then continued for 8 weeks, followed by a 4-week wash-out period. The primary efficacy endpoint was the change from baseline in the Consortium to Establish a Registry for Alzheimers Disease -Neuropsychological Battery (CERAD-NP) total score. Secondary efficacy endpoints included change from baseline in Functional Communication Language Inventory (FLCI) and ADCS-ADL19 total score, and the response from baseline in Clinical Global Impression of Change (CGI-C). The CERAD-NP total score improved significantly after 12 weeks of once-daily memantine treatment compared with baseline (5.9 ± 8.8; p < 0.0001). The FLCI total score improved significantly after 12 weeks compared with baseline (4.4 ± 6.8; p < 0.0001). These significant improvements were already observed after 4 and 8 weeks of once-daily memantine treatment and persisted after a 4-week wash-out period. ADCS-ADL19 total scores showed only slight increases from baseline, and CGI-C indicated that the majority of patients experienced an improvement or stabilization of the disease after 12 weeks. At least one Treatment-Emergent Adverse Event was reported by 38 (39.2%) patients. In patients with moderate to severe AD, once-daily memantine (20 mg) treatment significantly improved cognition and functional communication and was found to have a favorable safety and tolerability profile.

Validation of the relevant outcome scale for Alzheimer's disease: a novel multidomain assessment for daily medical practice

IntroductionThe Relevant Outcome Scale for Alzheimers Disease (ROSA) is a new observer rating instrument recently developed for routine medical practice. The validity and reliability of ROSA as well as sensitivity to changes due to intervention were examined in an open-label, single-arm, multicenter clinical study in patients with Alzheimers disease (AD).MethodsThe study enrolled 471 patients with a diagnosis of AD consistent with the criteria of the National Institute of Neurological and Communicative Disease and Stroke/Alzheimers Disease and Related Disorders Association or with the Diagnostic and Statistical Manual Disorders criteria for dementia of Alzheimers type. Following assessments of the ROSA and other standard assessments (Alzheimers Disease Assessment Scale - cognitive subscale, Severe Impairment Battery, Neuropsychiatric Inventory, and Disability Assessment for Dementia), patients were treated with memantine for 12 weeks. Factor analysis of the baseline ROSA total scores was performed based on the principal components method using the varimax orthogonal rotational procedure. The psychometric analyses of the ROSA included internal consistency, test-retest reliability, inter-rater reliability, construct validity, and responsiveness to changes over time.ResultsAll items showed adequate factor loadings and were retained in the final ROSA as Factor 1 (all items related to cognition, communication, function, quality of life and caregiver burden) and Factor 2 (all behavior items). The ROSA demonstrated high internal consistency (Cronbachs α = 0.93), test-retest reliability (intraclass correlation coefficient = 0.93), and inter-rater reliability (intraclass correlation coefficient = 0.91). The correlation coefficients between the ROSA and each of the validated scales ranged between 0.4 and 0.7, confirming the ROSA construct validity. Nonsubstantial floor and ceiling effects were found in middle and late disease stages, whereas a small ceiling effect was observed in the early stage. The ROSA responsiveness to change was high (responsiveness index ≥0.8) for all severity stages.ConclusionsThe ROSA is a valid and reliable instrument to aid medical practitioners in sensitively assessing AD-relevant symptoms over time in their clinical practice.

Severe Impairment Battery Language scale: A language-assessment tool for Alzheimer's disease patients

Communication problems are common in Alzheimers disease (AD) patients, but instruments to assess these symptoms are limited. Our objective was to create a new scale, based on the language subscale of the Severe Impairment Battery (SIB), as a sensitive and reliable measurement of treatment effects on language performance.

Detecting treatment effects with combinations of the ADAS-cog items in patients with mild and moderate Alzheimer's disease.

When complex cognitive functions are measured with multi‐item scales like the Alzheimers Disease Assessment Scale – cognitive subscale (ADAS‐cog), it seems valuable information can be lost due to combination of the ADAS‐cog items results into a total score. We hypothesized, that an analysis of the results of different ADAS‐cog item combinations may reveal drug treatment effects in distinct cognitive domains and/or enhance the sensitivity to detect such treatment effects. Here, we present a novel approach called ‘subsetting analysis’ for assessment of drug treatment effects with multi‐item scales, like the ADAS‐cog.

Memantine effects measured with the Relevant Outcome Scale for Alzheimer's disease in an open-label, single-arm, multicenter clinical study

The Relevant Outcome Scale for Alzheimers disease (ROSA) is a novel, valid, and reliable instrument for multidimensional assessment of Alzheimers disease (AD) symptoms across all severity stages. The ROSA and four standard instruments — the Alzheimers disease Assessment Scale‐cognitive (ADAS‐cog), Severe Impairment Battery (SIB), Disability Assessment for Dementia (DAD), and the Neuropsychiatric Inventory (NPI) — were used in an open‐label, multicenter, single‐arm clinical study to assess treatment‐induced changes in cognitive, functional, and behavioral symptoms in patients with AD at different severity stages.

Once-daily memantine treatment improves cognition and functional communication in patients with moderate to severe AD: Results of a 16-week, single-arm, open-label trial

controlled trials and 495 controlled clinical trials in dementia and cognitive impairment. As at 1st April 2009 this includes all completed, ongoing and aborted studies identified by sensitive monthly searches. As well as citations, the displayed data include: study design/blinding, participants and health condition, intervention and dosage, number of participants, outcomes, date of study, website links and related Cochrane reviews/protocols. Conclusions: ALOIS is an online study-based register which will supply review authors, investigators, researchers and other stakeholders with a unique and upto-date source of all published and unpublished studies in the area of dementia treatment/prevention and cognitive enhancement. The site will be launched online in June 2009. Funded by Alzheimer’s Association, USA.

Memantine treatment reduces the intake of concomitant antipsychotics in patients with moderate Alzheimer's disease

were also observed (Figure B and C, respectively) and were companied with increased TH, VMAT2 and dopamine levels. To confirm that Cu (atsm) exhibits its therapeutic effects via inhibition of nitrosative stress, Cu (atsm) was able to rescue toxicity and inhibit increases in nitrotyrosine levels in differentiated SH-SY5Y cells treated with 3-morpholinosydnonimine (SIN-1), a compound causes nitrosative stress. Conclusions: These findings establish the therapeutic effects of Cu (btsc) compounds in animal models and suggest that these compounds could be effective disease modifying agents for neurodegenerative diseases.

The need for a new practical Alzheimer's disease scale

Conclusions: Results on safety and adherence will be presented at the time of the meeting. P1-049 THE NEED FOR A NEW PRACTICAL ALZHEIMER’S DISEASE SCALE Philippe Robert, Steven Ferris, Serge Gauthier, Gudrun Gatz, Bengt Winblad, Frank Tennigkeit, Université de Nice Sophia Antipolis, Nice, France; Alzheimer’s Disease Center, New York University School of Medicine, NY and Nathan Kline Institute, Orangeburg, NY, USA; McGill Centre for Studies in Aging, Montreal, QC, Canada; Merz Pharmaceuticals, Frankfurt am Main, Germany; Karolinska Institutet, Alzheimer Center, Stockholm, Sweden. Contact e-mail: philippe.robert15@wanadoo.fr Background: Alzheimer’s disease (AD) leads to progressive loss of everyday competence and heterogeneous symptoms. This bears a challenge for an adequate and comprehensive assessment instrument for daily medical practice and care of patients with AD. Objectives: To evaluate the requirements for a multi-domain AD scale to be used in daily clinical practice, and analyze the existing scales which may meet these demands. Methods: A national expert panel comprising medical and caregiver experts was consulted to define requirements for an AD scale in medical practice. An extensive literature search was subsequently performed to identify existing scales fulfilling these requirements. The results were evaluated and discussed by the international expert panel. Results: The extensive literature search showed that most scales used in AD research so far do not comprise all relevant domains, are not applicable to all severity stages and are often time-consuming and difficult to administer. In view of these results and from the comprehensive discussions at the expert panel meetings, it was concluded that an ideal scale in medical AD practice should allow easy and quick administration and cover the following relevant domains: cognition, activities of daily living, behavior, communication/social interaction, quality of life and caregiver burden. The information of patient and caregiver should be taken into account. Such a scale should also enable monitoring of disease progression and the assessment of therapy effects; it should be applicable to all severity stages, reliable and validated for AD research. Conclusions: It appears that a multi-domain and easy-administrable AD scale for daily medical practice does not exist so far. There is a need to develop a valid scale for medical AD practice which should cover all the relevant domains and severity stages, allow easy and quick administration, enable monitoring of disease progression and the assessment of therapy effects. P1-050 CLINICAL PROFILE OF ALZHEIMER’S DISEASE (AD)-A STUDY FROM NORTH INDIA Suman Kushwaha, Sunil Pradhan, D. C. Jain, Meena Gupta, Kiran Bala, Institute of Human Behavior & Allied Sciences, Delhi, India. Contact e-mail: sumankushwaha@gmail.com Background: Alzheimers Disease, heterogenous & progressive disorder. It is emerging as a modern pandemic. It is important to recognize this treatable disease early in course for reducing the burden on healthcare services. Methods: Objective To study the clinical profile, therapeutic interventions and outcome of AD Patients. Material & Method Duration 5 yrs (20032008). Study was done at Neurobehavioural Clinic, Neurology Department, Pts were evaluated clinically by taking history. Examination includes MMSE Scores, higher mental status & Neurological & Neuropsychological assessment. Routine Laboratory test, thyroid function, Vit B12, folic acid & Homocystine levels were done for co morbid conditions. Neuroimaging done in all patients. Patients were given specific treatment & followed for an average period of 2-4 yrs. Results: No of pts -164. Age range is 50 -90 yrs. Male 70, Female 94. Duration of illness 4 months to 5.6 yrs. Memory impairment was commonest presentation, 120 pts (73%) followed by Behavioural disturbances in 64%. The pts were sub divided into three categories on MMSE score Mild, Moderate & Severe. Higher mental functions assessment revealed temporal & parital lobe dysfunctions in 70% of pts. Neuropsychiatry inventory showed depression and agitation in severe group. Motor system examination was grossly normal. All the pts fulfilled NINCDS-ADARDA Criteria Laboratory investigations shows Vit B12 deficiency in 20% pts. 35% were Diabetic, Hyperhomocystenemia in 10% while Raised Cholesterol levels in 18%. MRI/CT was done in all patients, showing generalised atrophy of varying degree. SPECT brain revealed hypoperfusion in temporal, frontal & parital area in pts of early dementia.. Choline esterase inhibitors was given to all pts with NMDA receptor antagonist to 28 pts. Antipsychotics were given to 40% pts. Co morbid conditions treated. Out come on 2-4 yrs follow up shows improvement in 34(21%) Behaviour, ADLs & cognition ,66 pts (42%) stable. 28% deteriorated, 15% pts lost follow up. Conclusions: AD is clinically diagnosable and treatable disorder. Early and correct diagnosis along with timely interventions with available treatment options will be helpful in reducing the burden of this modern pandemic. P1-051 APPLICATION OF AD-8 TO SCREEN VERY MILD DEMENTIA IN TAIWAN Ching-Kuan Liu, Mei-Chuan Chou, Chiou-Lian Lai, Yuan-Han Yang, Kaohsiung Medical University, Kaohsiung, Taiwan. Contact e-mail: ckliu@ kmu.edu.tw Background: By 2040, Asia will have the highest prevalence of dementia compared to other area. Physicians hope the demented patients can be diagnosed at their earlier stage in order to have desirable therapeutic outcomes. Therefore, easy-to-administer sensitive clinical tools to screen whether people have very mild dementia are expected. The AD-8 scale was developed with higher sensitivity and specificity from Washington University in St Louis to efficiently capture individuals at their very mild dementia. The AD8 is a brief informant-based measure that reliably differentiates non-demented from demented individuals and is sensitive to the earliest signs of cognitive change as reported by an informant. However, given to the different cultural background, we do not know whether the AD-8 is practicable to screen very mild dementia in Taiwanese. We conduct a study to examine the application of AD-8 to screen very mild dementia in Taiwanese. Methods: Participants were recruited from Alzheimer’s disease research center in Kaohsiung Medical University Hospital, a medical center in southern Taiwan. Diagnosis of dementia of Alzheimer’s type was made according to DSM-IV criteria and referring to neuropsychological test. The English-version AD-8 questionnaire was translated into Chinese and back translated to English to make sure the translative accuracy. For each participant, the clinical dementia rating (CDR) scale and AD-8 were administrated simultaneously during their each assessment. Receiver operating characteristic (ROC) curve was conduct to determine the cut-off values of Chinese version AD-8 in discriminating non-demented from very mild or mild dementia participants. Results: Two hundreds and thirty-nine participants, including 114 non-demented (CDR0), 73 very mild dementia (CDR0.5), and 52 mild dementia (CDR1) were recruited. The cut-off value of discriminating non-demented subjects (CDR 0) from very mild dementia (CDR 0.5) or from dementia (CDR0.5 and CDR1) was 2 in both groups. The sensitivity 95.89%, specificity 78.07%, and area under curve (AUC) 0.948 were high in discriminating CDR 0 from CDR 0.5 group. In CDR0 versus CDR0.5 and CDR1 group, the sensitivity and specificity were 97.6% and 78.07%, respectively, and AUC was 0.961. Conclusions: AD-8 is a brief and sensitive instrument that can reliably differentiate non-demented from demented, even in very mild stage, subjects in Taiwanese. P1-052 THE CLINICAL CHARACTERISTICS OF THE JAPANESE PEDIGREE OF FAD WITH PS1 H163R MUTATION Toji Miyagawa, Atsushi Iwata, Hisatomo Kowa, Takeshi Kawarabayashi, Mikio Shoji, Shoji Tsuji, Toshimitsu Momose, Yoshiki Kojima, University of Tokyo, Tokyo, Japan; Hirosaki University, Hirosaki, Aomori, Japan; Hirosaki University, Hirosaki, Aomoni, Japan; University of Tokyo, Bunkyo-ku, Japan. Contact e-mail: tmiyagawa-tky@ umin.ac.jp Background: The mutations of Presenilin 1 (PS1) are the most common genetic cause of familial Alzheimer’s disease (FAD), but few detailed descriptions of the clinical phenotype have been reported. Methods: We investigated phenotypic variations of the FAD with H163R mutation in PS1 by examining the 2 patients including neuropsychological profile and taking histories of other 12 patients from family members. Genetic analyses