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OBJECTIVE: Currently no standardized tools are available in the Indian languages to assess changes in cognition. Our objectives are to culturally adapt the Alzheimer’s disease Assessment Scale – Cognitive Subscale (ADAS-Cog) for use in India and to validate the Tamil version in an urban Tamil-speaking older adult population. METHODS: Two panels of key stakeholders and a series of qualitative interviews informed the cultural and linguistic adaptation of the ADAS-Cog-Tamil. Issues related to levels of literacy were considered during the adaptation. Validation of the ADAS-Cog-Tamil was completed with 107 participants - 54 cases with a confirmed diagnosis of mild-moderate dementia, and 53 age, gender, and education matched controls. Concurrent validity was examined with the Vellore Screening Instrument for Dementia (VSID) in Tamil. Internal consistency using Cronbach’s alpha, sensitivity, and specificity data using the Area Under the Receiver Operating Characteristics (AUROC) curve values were computed. Inter-rater reliability was established in a sub-sample. RESULTS: The ADAS-Cog-Tamil shows good internal consistency (α=0.91), inter-rater reliability, and concurrent validity (with VSID-Patient version: r=-0.84 and with VSID-Caregiver version: r=-0.79). A cut-off score of 13, has a specificity of 89% and sensitivity of 90% for the diagnosis of dementia. CONCLUSION: ADAS-Cog-Tamil, derived from a rigorous, replicable linguistic and cultural adaptation process involving service users and experts, shows good psychometric properties despite the limitations of the study. It shows potential for use in clinical settings with urban Tamil speaking populations. The English version of the tool derived from the cultural adaptation process could be used for further linguistic adaptation across South Asia.

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia where the most prominent cognitive impairment is memory loss. Screening tests are valuable tools for detecting cognitive impairment. One such test is the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) which consists of 11 tasks. The main goal of our study was to validate the Slovenian version of the ADAS-Cog for detecting mild cognitive impairment (MCI) and AD patients. Our sample included 128 participants: 61 healthy controls, 32 people with MCI, and 35 with AD. All participants were evaluated with the Slovenian translation of ADAS-Cog. The optimal cut-off for the ADAS-Cog for MCI was 10/11 points. The sensitivity was 88%, specificity 85% and likelihood ratio 6. The optimal cut-off for AD was 11/12 points. Sensitivity was 100%, specificity 95% and likelihood ratio 20. The obtained cut-off values are comparable to the results from similar validation studies. We can conclude that the ADAS-Cog is a reliable and valid tool for identifying people with MCI and AD from among healthy controls in the Slovenian population.

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) was developed in the 1980s to assess the level of cognitive dysfunction in Alzheimer's disease. Advancements in the research field have shifted focus toward pre-dementia populations, and use of the ADAS-Cog has extended into these pre-dementia studies despite concerns about its ability to detect important changes at these milder stages of disease progression. If the ADAS-Cog cannot detect important changes, our understanding of pre-dementia disease progression may be compromised and trials may incorrectly conclude that a novel treatment approach is not beneficial. The purpose of this review was to assess the performance of the ADAS-Cog in pre-dementia populations, and to review all modifications that have been made to the ADAS-Cog to improve its measurement performance in dementia or pre-dementia populations. The contents of this review are based on bibliographic searches of electronic databases to locate all studies using the ADAS-Cog in pre-dementia samples or subsamples, and to locate all modified versions. Citations from relevant articles were also consulted. Overall, our results suggest the original ADAS-Cog is not an optimal outcome measure for pre-dementia studies; however, given the prominence of the ADAS-Cog, care must be taken when considering the use of alternative outcome measures. Thirty-one modified versions of the ADAS-Cog were found. Modification approaches that appear most beneficial include altering scoring methodology or adding tests of memory, executive function, and/or daily functioning. Although modifications improve the performance of the ADAS-Cog, this is at the cost of introducing heterogeneity that may limit between-study comparison.

The Alzheimer's disease assessment scale-Cognitive Subscale (ADAS-Cog) is a battery to assess cognitive performance in Alzheimer's disease (AD) and was developed according to the core characteristics of cognitive decline in AD: memory, language, praxis, constructive ability, and orientation. The aim of this study was to explore the diagnostic accuracy and discriminative capacity of the ADAS-Cog for Mild Cognitive Impairment (MCI) and AD, using cut-off points for the Portuguese population.The European Portuguese version of the ADAS-Cog was administrated to 650 participants, divided into a control group (n = 210), an MCI group (n = 240), and an AD group (n = 200). The clinical groups fulfilled standard international diagnostic criteria. Controls were healthy cognitive participants actively integrated in the community. The neuropsychological assessment protocol included the ADAS-Cog, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Adults and Older Adults Functional Assessment Inventory (IAFAI).The ADAS-Cog revealed good psychometric indicators, and the total scores were significantly different between the three groups (p .001: Control MCI AD). The optimal cut-off points established were: MCI 9 points (AUC = .835; sensitivity = 58% and specificity = 91%) and AD 12 points (AUC = .996; sensitivity = 94% and specificity = 98%).Our findings confirmed the capacity of the ADAS-Cog total score to identify cognitive impairment in AD patients, with poor sensitivity for MCI, in a Portuguese cohort.

Introdução: A Escala de Avaliação da Doença de Alzheimer – subescala cognitiva (ADAS-Cog) é uma bateria neuropsicológica breve desenvolvida para caracterizar o desempenho cognitivo de doentes com doença de Alzheimer. Avalia as funções tipicamente mais comprometidas na doença de Alzheimer considerando os seguintes domínios cognitivos: memória, orientação, linguagem, praxia e capacidade construtiva. A deteção precoce das alterações cognitivas assim como a sua monitorização são fundamentais para a prática em ambos os contextos clínico e de investigação. O presente estudo tem como objetivos analisar as propriedades psicométricas da versão portuguesa da Escala de Avaliação da Doença de Alzheimer – subescala cognitiva e estabelecer dados normativos para a população portuguesa.Material e Métodos: A versão portuguesa da Escala de Avaliação da Doença de Alzheimer – subescala foi administrada a 223 participantes cognitivamente saudáveis. Todos os participantes foram avaliados com os seguintes instrumentos: Mini-Mental State Examination, Montreal Cognitive Assessment e Inventário de Avaliação Funcional de Adultos e Idosos. Considerou-se como critério para a inclusão no estudo obter um desempenho normal nestas três provas.Resultados: A Escala de Avaliação da Doença de Alzheimer – subescala revelou boas propriedades psicométricas quando utilizada na população portuguesa. A idade demonstrou ser o principal preditor do desempenho na Escala de Avaliação da Doença de Alzheimer – subescala (R2 = 0,123), tendo a escolaridade menor influência (R2 = 0,027). Em conjunto, estas variáveis sociodemográficas explicaram 14,4% da variância na pontuação total da Escala de Avaliação da Doença de Alzheimer – subescala, sendo ambas consideradas na estratificação dos dados normativos para a população portuguesa.Conclusão: A pontuação total média na Escala de Avaliação da Doença de Alzheimer – subescala foi de 6 pontos. Os dados normativos foram estabelecidos de acordo com a idade e escolaridade, sendo estas variáveis sociodemográficas as que mais contribuíram para a predição do desempenho na Escala de Avaliação da Doença de Alzheimer – subescala, explicando 14,4% da variância. Os dados normativos são de extrema importância para o uso adequado desta bateria em Portugal.

Background: LMTM is being developed as a treatment for AD based on inhibition of tau aggregation. Objectives: To examine the efficacy of LMTM as monotherapy in non-randomized cohort analyses as modified primary outcomes in an 18-month Phase III trial in mild AD. Methods: Mild AD patients (n = 800) were randomly assigned to 100 mg twice a day or 4 mg twice a day. Prior to unblinding, the Statistical Analysis Plan was revised to compare the 100 mg twice a day as monotherapy subgroup (n = 79) versus 4 mg twice a day as randomized (n = 396), and 4 mg twice a day as monotherapy (n = 76) versus 4 mg twice a day as add-on therapy (n = 297), with strong control of family-wise type I error. Results: The revised analyses were statistically significant at the required threshold of p

The purpose of this study was to estimate and examine ways to improve the reliability of change scores on the Alzheimer's Disease Assessment Scale, Cognitive Subtest (ADAS-Cog). The sample, provided by the Alzheimer's Disease Neuroimaging Initiative, included individuals with Alzheimer's disease (AD) (n = 153) and individuals with mild cognitive impairment (MCI) (n = 352). All participants were administered the ADAS-Cog at baseline and 1 year, and change scores were calculated as the difference in scores over the 1-year period. Three types of change score reliabilities were estimated using multivariate generalizability. Two methods to increase change score reliability were evaluated: reweighting the subtests of the scale and adding more subtests. Reliability of ADAS-Cog change scores over 1 year was low for both the AD sample (ranging from .53 to .64) and the MCI sample (.39 to .61). Reweighting the change scores from the AD sample improved reliability (.68 to .76), but lengthening provided no useful improvement for either sample. The MCI change scores had low reliability, even with reweighting and adding additional subtests. The ADAS-Cog scores had low reliability for measuring change. Researchers using the ADAS-Cog should estimate and report reliability for their use of the change scores. The ADAS-Cog change scores are not recommended for assessment of meaningful clinical change.

Resume–Contexte Contexte Les modalites d’arret des medicaments specifiques de la demence(MSD) ne font pas l’objet d’un consensus. Objectifs Les objectifs de l’etude etaient de : decrire i) les motifs et modalites d’arret des MSD des patients traites en Etablissement Hospitalier pour Personnes Âgees Dependantes (EHPAD), ii) la securite d’emploi d’un arret brutal, iii) et l’evolution des troubles. Methodes Nous avons etudie des sujets atteints de la maladie d’Alzheimer a un stade modere a severe, vivants en institution et traites depuis au moins 1 an par rivastigmine, donepezil, galantamine et/ou memantine. Sur decision pluridisciplinaire selon les recommandations de la Haute autorite de sante (HAS), les traitements MSD ont ete arretes soudainement ou poursuivis. Les criteres de jugement suivants ont ete recueillis prospectivement sur six mois : les motifs d’arret, les donnees de securite, le score mini-mental state examination (MMSE), les troubles psycho-comportementaux et la prescription concomitante de psychotropes. Resultats Trente-trois patients ont ete inclus : la reevaluation du traitement a conduit a 22 arrets et 11 poursuites. Les motivations a l’arret etaient une demence trop evoluee (48 %), une absence de benefice therapeutique (28 %) et un traitement psychotrope associe trop lourd (24 %). La modalite d’arret soudain n’a entraine aucun syndrome de sevrage. La variation du MMSE a 6 mois etait de -1,8 (SD 2,2) dans le groupe arret (n = 14) et -2,2 (SD 2,0) dans le groupe poursuite (n = 6). Dans le groupe « arret », un allegement des traitements psychotropes a ete observe. Conclusion Dans cette etude pilote realisee en institution, la reevaluation conforme aux recommandations de la HAS a conduit a 2 arrets sur 3 du traitement MSD. La securite de l’arret soudain des MSD reste a etudier.

The use of Panax ginseng and Panax quinquefolius in traditional Chinese medicine dates back to about 5000 years ago thanks to its several beneficial and healing properties. Over the past few years, extensive preclinical and clinical evidence in the scientific literature worldwide has supported the beneficial effects of P. ginseng and P. quinquefolius in significant central nervous system, metabolic, infectious and neoplastic diseases. There has been growing research on ginseng because of its favorable pharmacokinetics, including the intestinal biotransformation which is responsible for the processing of ginsenosides - contained in the roots or extracts of ginseng - into metabolites with high pharmacological activity and how such principles act on numerous cell targets. The aim of this review is to provide a simple and extensive overview of the pharmacokinetics and pharmacodynamics of P. ginseng and P. quinquefolius, focusing on the clinical evidence which has shown particular effectiveness in specific diseases, such as dementia, diabetes mellitus, respiratory infections, and cancer. Furthermore, the review will also provide data on toxicological factors to support the favorable safety profile of these medicinal plants., Highlights • P. ginseng and P. quinquefolius have been extensively studied for their beneficial effects. • Compound K, produced by the intestinal deglycosylation of ginseng, is a metabolite with pharmacological effects. • Clinical studies unraveled the positive effects of ginseng on cognitive skills, fatigue and glucose metabolism. • Further clinical studies are necessary to better characterize the potential therapeutic effect of ginseng. • Toxicological studies demonstrated the good safety profile of ginseng.

The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in prevention of Alzheimer’s disease (AD) has been evaluated in many studies. We performed a meta-analysis to summarize the existing evidence on the relation between use of classical NSAIDs and AD. Randomized controlled trials (RCTs) evaluating the role of classical NSAIDs in AD was searched using different search engines. The RCTs in patients who had the degree of AD measured on Mini-Mental State Examination (MMSE) or AD Assessment Scale-Cognitive subscale (ADAS-cog) were included in the study. The RCTs and data (AD scores) were independently assessed by 2 reviewers, and data were included in meta-analysis only after a common consensus was reached. The pooled results from the ADAS-cog and MMSE scores failed to show any difference between the treatment and the placebo groups as opposed to findings from some observational studies. However, in view of heterogeneity of results, there is a need to conduct more RCTs to arrive at confirmatory findings.

Purpose This work investigates improved utilization of ADAS-cog data (the primary outcome in Alzheimer’s disease (AD) trials of mild and moderate AD) by combining pharmacometric modeling and item response theory (IRT). Methods A baseline IRT model characterizing the ADAS-cog was built based on data from 2,744 individuals. Pharmacometric methods were used to extend the baseline IRT model to describe longitudinal ADAS-cog scores from an 18-month clinical study with 322 patients. Sensitivity of the ADAS-cog items in different patient populations as well as the power to detect a drug effect in relation to total score based methods were assessed with the IRT based model. Results IRT analysis was able to describe both total and item level baseline ADAS-cog data. Longitudinal data were also well described. Differences in the information content of the item level components could be quantitatively characterized and ranked for mild cognitively impairment and mild AD populations. Based on clinical trial simulations with a theoretical drug effect, the IRT method demonstrated a significantly higher power to detect drug effect compared to the traditional method of analysis. Conclusion A combined framework of IRT and pharmacometric modeling permits a more effective and precise analysis than total score based methods and therefore increases the value of ADAS-cog data. Electronic supplementary material The online version of this article (doi:10.1007/s11095-014-1315-5) contains supplementary material, which is available to authorized users.

Alzheimer’s disease (AD) patients treated with rivastigmine transdermal patch have shown statistically significant differences versus placebo on the AD Assessment scale-cognitive subscale (ADAS-cog). In this retrospective analysis of a double-blind, placebo- and active-controlled, 24-week clinical trial, the specific effects of rivastigmine patch on individual ADAS-cog items and cognitive domains (memory, language, and praxis) were explored. The mean baseline to week 24 changes were calculated for each ADAS-cog item and domain in this exploratory, hypothesis-generating analysis. Patients on 9.5 mg/24 h rivastigmine patch, 17.4 mg/24 h rivastigmine patch, and 3 to 12 mg/d rivastigmine capsules showed improvements over placebo on the memory and praxis ADAS-cog subscales. The rivastigmine patch groups also showed improvements on the language subscale. Significant differences versus placebo were seen on several individual item scores in the rivastigmine-treated groups. Rivastigmine patch was associated with improvements on the memory, praxis, and language domains of cognition in patients with mild-to-moderate AD.

Rivastigmine has been shown to improve cognition in patients with Parkinson’s disease dementia (PDD). To further explore the impact of anticholinesterase therapy on PDD, Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) items were assessed in a retrospective analysis of a 24-week, double-blind, placebo-controlled trial of rivastigmine. Mean changes from baseline at week 24 were calculated for ADAS-cog item scores and for 3 cognitive domain scores. A total of 362 patients were randomized to 3 to 12 mg/d rivastigmine capsules and 179 to placebo. Patients with PDD receiving rivastigmine improved versus placebo on items: word recall, following commands, ideational praxis, remembering test instructions, and comprehension of spoken language (P < .05), with standardized mean differences ranging from 0.04 to 0.30. Rivastigmine also showed significant effects versus placebo on all domains: memory, language, and praxis. The ADAS-cog is sensitive to broad cognitive changes in PDD. Overall, rivastigmine was associated with improvements on individual cognitive items and general cognitive domains.

Objective: Aim of this study was to compare ADAS-Cog and MDB, instruments usually used in cognitive assessment of AD patients, relative to: 1) diagnostic sensitivity for dementia of AD; 2) ability to rate the progression of cognitive decline and ability to detect the qualitative characteristics of cognitive decline. Material and methods: A sample of 54 AD patients was submitted to a cognitive assessment with both battery at time of study entry (T 0) and after 12 months (T 12). Results: This study showed: 1) a better diagnostic sensitivity of MDB respect to ADAS-Cog in diagnosing patients affected by mild to moderate levels of AD; 2) a better sensitivity of ADAS-Cog to follow the cognitive decline over a twelve-months period Conclusion: These results supports the use of the MDB in the screening phase of AD patients and of ADAS-Cog to follow the progression of cognitive decline over time.

female and 78 male (age 72,31 Std 8,29 , instruction 8,6 Std 3.9) of which 104 have no cognitive pathology (control group); 49 subjects withMCI clinical diagnosis and 66 with mild/ moderate AD.The control group was evaluated with a General Cognitive Screening (Adas Cog) and MMSS. We established a cut point of 26 for the MMSS and normal performance in Adas Cog.An Anova analysis has been carried out considering the number of clusters, number of switching, number of exemplars and clusters size in the three groups.Results:The ANOVA analysis showed that: exemplars number, cluster and switching number are significant variables to identify the EA, MCI and Control groups. It was significant (Pr (>F) 1⁄4 .001) to distinguish between the means of the Control Group (8.23), MCI (5.18) and EA (3.64). It was also relevant the ANOVA of switchings (Pr (>F) 1⁄4 .001): Control Group (10.1), MCI (6.59) and EA (5.36). The cluster size distinguished the control group from MCI and EA , but not between them. Conclusions: The results obtained constitute a significant contribution to the knowledge of the normal and pathological lexical processing. The study of the clusters’organization in semantic fluency tasks might provide a new important marker in the clinical diagnosis profile of MCI patients.

To conduct a psychometric analysis to determine the adequacy of instruments that measure cognition in Alzheimer's disease trials.Both the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and the Neuropsychological Test Battery (NTB) are validated outcome measures for clinical trials in Alzheimer's disease and are approved also for regulatory purposes. However, it is not clear how comparable they are in measuring cognitive function. In fact, many recent trials in Alzheimer's disease patients have failed and it has been questioned if ADAS-Cog still is a sensitive measure.The present paper examines the psychometric properties of ADAS-Cog and NTB, based on a post hoc analysis of data from a clinical trial (NCT01024660), which was conducted by AstraZeneca, in mild-to-moderate Alzheimer's disease (AD) patients, with a Mini Mental State Examination (MMSE) Total score 16-24. Acceptability, reliability, different types of validity and ability to detect change were assessed using relevant statistical methods. Total scores of both tests, as well as separate domains of both tests, including the Wechsler Memory Scale (WMS), Rey Auditory Verbal Learning Test (RAVLT) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Condition, were analyzed.Overall, NTB performed well, with acceptable reliability and ability to detect change, while ADAS-Cog had insufficient psychometric properties, including ceiling effects in 8 out of a total of 11 ADAS-Cog items in mild AD patients, as well as low test-retest reliability in some of the items.Based on a direct comparison on the same patient sample, we see advantages of the NTB compared with the ADAS-Cog for the evaluation of cognitive function in the population of mild-to-moderate AD patients. The results suggest that not all of ADAS-Cog items are relevant for both mild and moderate AD population.This validation study demonstrates satisfactory psychometric properties of the NTB, while ADAS-Cog was found to be psychometrically inadequate.

of accurately predicting prodromes of different dementia syndromes, we examined whether empirically-derived cognitive subtypes of MCI were consistent with consensus diagnoses (i.e., amnestic and non-amnestic singleand multi-domain; Winblad et al., 2004) and whether resulting neuropsychological profiles vary based on the criteria used for MCI diagnosis. Methods: 135 participants were diagnosed with MCI using conventional criteria (i.e., 1.5 SDs below normal on one test within a cognitive domain; Petersen & Morris, 2005) and 81 participants were diagnosed with MCI using comprehensive criteria developed to increase diagnostic specificity (i.e., 1 SD below normal on two tests within one domain; Jak et al., 2009). To examine tests and underlying cognitive constructs that constitute subgroup profiles, we conducted a hierarchical cluster analysis using 13 measures of language, memory, executive function, visuospatial function, and attention. Results: The conventional criteria for MCI yielded the following three distinct groups: An Amnestic subgroup (n 1⁄4 57) mildly impaired primarily on memory measures; a Mixed or multi-domain subgroup (n 1⁄4 14) impaired on memory, executive function, language, and visuospatial measures; and a Relatively Normal subgroup (n 1⁄4 64) that performed within normal limits. Of the MCI participants diagnosed via comprehensive criteria, four distinct groups emerged: An Amnestic MCI subgroup (n 1⁄4 30), a Dysexecutive MCI subgroup (n 1⁄4 13), a Mixed MCI subgroup (n1⁄4 19), and a Visuospatial subgroup (n1⁄4 19) impaired on a specific visuospatial measure. Conclusions: Findings revealed that neuropsychological profiles vary depending on classification scheme used to define MCI. The conventional criteria produced subgroups consistent with single and multi-domain amnestic MCI diagnoses. However, one subgroup performed largely within normal limits suggesting that using an isolated poor performance for diagnosis may increase risk for false positives. Comprehensive criteria revealed more nuanced subgroups characterized by memory as well as dysexecutive and visuoconstructional impairments. Both schemes revealed a Mixed subgroup consistent with a prodromal AD profile and more severe impairments that may reflect a later stage of MCI.