The validity and reliability of the Turkish version of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) in patients with mild and moderate Alzheimer's disease and normal subjects

OBJECTIVES: The cognitive subscale of the Alzheimer's Disease Assesment Scale (ADAS-Cog) is the most widely used test in clinical trials dealing with Alzheimer's disease (AD). The aim of this study was to investigate the validity and reliability of the Turkish version of ADAS-Cog. METHODS: Twenty-nine patients with AD, fulfilling NINCDS-ADRDA criteria of probable AD, who were in stage 3-5 according to the Global Deterioration Scale (GDS), and 27 non-demented control subjects with similar age, gender and educational status were recruited for the study. The Turkish version of ADAS-Cog, Standardized Mini Mental Status Examination (MMSE) and Short Orientation-Memory-Concentration Test (SOMCT) were applied to both of the groups. Inter-rater reliability, internal consistency, test-retest reliability; face validity, differential validity and convergent validity were statistically analyzed. RESULTS: Both MMSE and ADAS-Cog have significantly differentiated patients with AD and control subjects (p < 0.001). A significant correlation was established between MMSE and ADAS-Cog scores in AD group (r: -0.739). ADAS-Cog was also highly significantly correlated with GDS (r: 0.720) and SOMCT (r: 0.738). For the group with AD, control and whole cohort coefficients of internal consistency, Cronbach's alpha: 0.800, 0.515, 0.873 were found respectively. Inter-rater reliability for total ADAS-Cog score was found as ICC: 0.99 and 0.98 and test-retest reliability was found as ICC: 0.91 and 0.95 for demented and nondemented subjects, respectively. CONCLUSION: The Turkish version of ADAS-Cog has been found to be highly reliable and valid in differentiating patients with mild and moderate AD from nondemented subjects.     

北京城郊老人阿尔茨海默病评定量表认知部分中文版评分分布模式研究

目的 探讨阿尔茨海默病评定量表认知部分(ADAS-Cog)中文版评分在健康老人中的分布模式及其影响因素,并考查ADAS-Cog评分区分轻度AD和健康老人的灵敏度和特异度.方法 纳入健康老人(NC组)1616名、非痴呆易混淆老年患者(ND组)125例及AD患者310例(符合NINCDS-ADRDA很可能AD诊断标准,轻度201例,中度109例)为被试,所有被试接受ADAS-Cog测查.结果 NC组不同年龄组和不同受教育年限组间评分差异均有统计学意义,分别以80岁以上组和受教育年限为0～5年组评分最高.NC组ADAS-Cog总分与年龄、受教育年限有关,差异具有统计学意义(F=14.34、113.27,均P<0.01);轻度AD组ADAS-Cog评分与年龄和受教育年限无关;中度AD组和ND组ADAS-Cog总分与受教育年限有关,差异具有统计学意义(F=4.18、8.72,均P<0.05).ADAS-Cog评分能在一定程度上区分不同年龄组(曲线下面积0.69～0.82)和不同受教育组(曲线下面积0.75～0.88,以≥15年组最高)轻度AD与健康老人.结论 ADAS-Cog中文版总分在健康老年人群中的分布与年龄和受教育年限有关;ADAS-Cog适用于我国AD患者认知功能评估;ADAS-Cog评分在一定程度上可有效区分轻度AD与健康老人,尤其适用于高文化水平者.     

The Alzheimer's Disease Assessment Scale-Cognitive subscale: normative data for older adult controls

The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) is commonly used to assess cognitive dysfunction in individuals with Alzheimer disease and other dementias. The purpose of this study was to provide normative scores for the ADAS-cog 11 individual items and total score, as well for delayed recall errors, using normal, elderly volunteers. The ADAS-cog was administered to 124, non-cognitively impaired volunteers ages 55 to 89, with 10 to 21 years of education. The mean total ADAS-cog score was five. The ADAS-cog error score was not associated with education in this highly educated group, and was positively correlated (P < 0.001) with the age of the participant. Age stratified ADAS-cog normative data are reported for the ADAS-cog total and the delayed recall error score.     

Predictors of placebo group decline in the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) in 24 week clinical trials of Alzheimer's disease

One limitation of several recent 24 week Alzheimer's disease (AD) clinical trials was the lack of cognitive decline detected by the AD Assessment Scale-cognitive subscale (ADAS-cog) in the placebo groups, possibly obscuring true medication effects. Data from 733 individuals in the placebo arms of six AD clinical trials performed 1996-1997 were pooled to examine the relationship of clinical, demographic, and genetic characteristics with the 24 week change in ADAS-cog. Baseline cognitive and functional status and the screening-to-baseline change in ADAS-cog were the strongest independent predictors of the 24 week change in ADAS-cog. The ADAS-cog did not detect progression in patients with mild dementia (screening Mini-Mental State Exam, MMSE, >or=20). The change in ADAS-cog from screening to baseline was inversely correlated with the 24 week change score; it was more difficult to detect cognitive decline at 24 weeks if individuals markedly worsened from screening to baseline. The effects of baseline MMSE and screening-to-baseline change in ADAS-cog generalized to the placebo group (N=106) of another AD study performed in 2004-2005. Overcoming lack of placebo decline in AD clinical trials will require scales more sensitive to cognitive decline in mild AD and strategies to reduce within-person variability in outcome measures.     

Assessing change in cognitive function in dementia: the relative utilities of the Alzheimer's Disease Assessment Scale-Cognitive Subscale and the Cognitive Drug Research system

This paper considers the suitability of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) as the gold standard in registration trials of treatments for Alzheimer's disease. Working groups have recommended replacing the ADAS-cog if suitable automated alternatives can be found. This paper makes the case for the Cognitive Drug Research (CDR) computerised cognitive assessment system, as an example of a suitable instrument to replace the ADAS-cog. The CDR system has been widely used in dementia work for 20 years and shows good correlations to the ADAS-cog, while additionally assessing the domains of attention, working memory, information processing and retrieval speed of information held in memory. The utility of the system in evaluating and differentiating the major dementias will be described, as well as its ability to track deterioration over time. Its validation as a core measure of cognitive dysfunction in the dementias will be described, as will work showing that various CDR measures relate closely to activities of daily living. The sensitivity of the CDR system to anticholinesterases will be described in Alzheimer's disease, dementia with Lewy bodies and Parkinson's dementia. Finally, the CDR system has a large normative database which allows treatment effects in dementia to be put into an unambiguous clinical perspective.     

Development of the Korean version of Alzheimer's Disease Assessment Scale (ADAS-K)

OBJECTIVE: The purpose of this study was the development of the Korean Version of Alzheimer's Disease Assessment Scale (ADAS-K). METHOD: ADAS-K was administrated to 84 AD patients as well as 105 non-demented control subjects. Three aspects of reliability were tested. To evaluate the validity of ADAS-K, discriminant validity and concurrent validity were tested. To evaluate the sensitivity of ADAS-K to disease severity, all subjects, AD patients and control subjects, were grouped by CDR scale and their mean scores on ADAS-K were compared. RESULT: ADAS-K demonstrated high levels of reliability. Mean ADAS-K scores for AD patients were significantly different from the control group (p < 0.01). Furthermore, ADAS-K exhibited significant correlations with other tests and scales (range 0.45-0.85, p < 0.01). In ROC curve analysis, ADAS-K displayed high diagnostic efficacy and the optimal cut-off point was selected between 18/19. ADAS-K was able to discriminate the degree of AD severity according to CDR classification. Our results suggested that ADAS-K-cog was sensitive to very mild AD. CONCLUSION: We demonstrated that ADAS-K is a reliable and valid instrument not only for AD diagnosis but also for evaluation of its severity.     

Prevalence of Alzheimer's type dementia in an elderly Arab population.

The aim of this study was to estimate the prevalence of dementia of the Alzheimer type (DAT) in an Arab Israeli community. Epidemiological studies of dementia have rarely been reported in Arab populations. The target population, aged 60 years or older, comprised 821 persons (362 males) who, on 1 October 1995, were residents of the rural area of Wadi Ara. These persons were examined for symptoms of dementia (DSM-IV criteria), using a semistructured questionnaire for collection of demographic and medical data. Age, gender, and education-specific prevalence rates were calculated for this population and compared to those obtained in other studies. DAT was diagnosed in 20.5% of this population. Its prevalence increased steeply with age, from 8% among those younger than 70 years to 33% among those aged 70-79 and 51% among those 80 years or older. Illiteracy was very common in this population, and strongly associated with higher prevalence of DAT (27% vs. 4%, P < 0.001). DAT was more prevalent among females than males (25% vs. 15%, P < 0.001). However, illiteracy was also significantly more frequent among women (96% vs. 42%, P < 0.001). After correction for illiteracy, the gender difference lost statistical significance. Few women smoked, but among men, the prevalence of DAT in those who smoked was lower as compared to non-smokers (14% vs. 23%, a non-significant difference). These results were confirmed by logistic regression wherein DAT was included as the dependent variable and age, illiteracy, gender and smoking as independent variables (OR=2.8, 2.8, 1.2 and 0.7, respectively; P < 0.005 for each, except for smoking). Our findings suggest that this population is unique because of extremely high rates of dementia. While the results support a protective effect of schooling against the development of dementia, other factors (e.g. genetic) must be sought to explain this high frequency.     

The Alzheimer's Disease Assessment Scale: findings from a low-education population.

We constructed a Chinese version of the cognitive component of the Alzheimer's Disease Assessment Scale (ADAS-Cog). In order to accommodate illiteracy, the Chinese version used pictures instead of words for assessing recall and recognition. The Chinese ADAS-Cog was administered to 125 individuals with no dementia, 127 with questionable dementia, and 77 with Alzheimer's disease (AD). Their age range was 51-92 years and their education range was 0-20 years. The Chinese ADAS-Cog had high internal consistency (Cronbach's alpha = 0.87) and very high interrater reliability (intraclass correlation coefficient, or ICC, = 0.99) and test-retest reliability (ICC = 0.96). It had high correlations with scores on the Clinical Dementia Rating Scale (Pearson's r = 0.85), the Cognitive Abilities Screening Instrument (CASI, Pearson's r = -0.88), and CASI-estimated scores on the Mini-Mental State Examination (Pearson's r = -0.85). Performance on the Chinese ADAS-Cog was uninfluenced by age or gender, nor by education level except within the low education range of 0-6 years. Its memory items were best for early detection of dementia; its language items were best for monitoring the progression of dementia. This study found that the Chinese ADAS-Cog is a good instrument for use with Chinese AD patients.     

Validity of different linguistic versions of the Alzheimer's Disease Assessment Scale in an international multicentre Alzheimer's disease trial.

Owing to the involvement of Italian Centres in a multicentre, German-Italian therapeutical trial with Alzheimer's dementia patients, to be assessed with the Alzheimer's Disease Assessment Scale (ADAS), it was decided that the Italian centres would use an Italian version of the scale, derived from that used by the German centres. However, the lists of words for exploring verbal memory are not merely translated from the German version, but are composed of selective Italian words chosen according to linguistic criteria. This Italian version was validated following the same procedure adopted for validating the German version. We submitted this Italian version to an interrater reliability, test-retest reliability, concurrent validity, internal consistency and sensitivity evaluation, using demented patients. Based on the results of these tests this Italian version of the ADAS proved valid and reliable. Moreover, the results were strikingly comparable to those from the validation of the German version. Our work supports the validity, reliability and transnational comparability of national versions of the ADAS constructed following definite linguistic criteria.     

Validity of the five-item WHO Well-Being Index (WHO-5) in an elderly population

Background Depression has a high prevalence in the elderly population; however it often remains undetected. The WHO 5-item Well-Being Index (WHO-5) is a short screening instrument for the detection of depression in the general population, which has not yet been evaluated. The goals of the present study were: 1) to assess the internal and external validity of WHO-5 and 2) to compare the two recent versions of WHO-5.Study population and methods 367 subjects above 50 years of age were examined with the WHO-5. ICD-10 diagnoses were made using a structured interview (CIDI). The internal validity of the well-being index was evaluated by calculating Loevinger’s and Mokken’s homogeneity coefficients. External validity for detection of depression was evaluated by ROC analysis.Results The scale was sufficiently homogeneous (Loevinger’s coefficient: version 1=0.38, version 2=0.47; Mokken coefficient τ; 0.3 in nearly all items). ROC analysis showed that both versions adequately detected depression. Version 1 additionally detected anxiety disorders, version 2 being more specific for detection of depression.Conclusion The WHO-5 showed a good internal and external validity. The second version is a stronger scale and was more specific for the detection of depression. The WHO-5 is an useful instrument for identifying elderly subjects with depression.

     

Montreal Cognitive Assessment (MoCA): normative study for the Portuguese population

The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening instrument with good psychometric features and an excellent sensitivity in the early detection of mild cognitive decline. The MoCA was applied to a community-based sample of cognitively healthy adults (n?=?650), stratified according to sociodemographic variables (age, gender, educational level, geographic region, geographic localization, and residence area), with a distribution similar to that observed in the Portuguese population. The normative data were determined according to age and education as these were the sociodemographic variables that most significantly contributed to the prediction of the MoCA scores, explaining 49% of their variance.     

Results of a follow-up study to the randomized Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT)

ObjectivesThe Alzheimer's Disease Anti-inflammatory Prevention Trial Follow-up Study (ADAPT-FS) was designed to evaluate the efficacy of naproxen and celecoxib for the primary prevention of Alzheimer's disease (AD) several years after cessation of treatment in ADAPT.MethodsADAPT was a randomized, double-masked, multicenter clinical trial of naproxen or celecoxib vs placebo (1:1:1.5 assignment ratio) at six U.S.-based clinics. The trial enrolled 2528 people between 2001 and 2004. Treatments were discontinued in December 2004 and participants were monitored regularly until 2007. In 2010 and 2011, ADAPT-FS screened 1537 participants by telephone and, if indicated, examined them in person using standardized clinical assessments. The primary outcome was time to diagnosis of AD. Death index searches were performed for participants not located.ResultsEighty-nine additional AD events were identified (24 celecoxib, 25 naproxen, and 40 placebo) yielding a total of 161 events (48 [6.6% of randomized participants] celecoxib, 43 [6.0%] naproxen, and 70 [6.5%] placebo) across ADAPT and ADAPT-FS. Adjusted hazard ratios (HRs) comparing each treatment with placebo showed no overall reduction in risk of AD: HR celecoxib vs placebo, 1.03 (95% confidence interval [CI], 0.72–1.50; P = .86); HR naproxen vs placebo, 0.92 (95% CI, 0.62–1.35; P = .66). There were 349 deaths (110 [15.2%] celecoxib, 96 [13.4%] naproxen, and 143 [13.2%] placebo). Risk of death was similar for the naproxen- and placebo-assigned groups (HR, 0.99; 95% CI, 0.76–1.28; P = .93) and slightly higher for celecoxib compared with the placebo-assigned group (HR, 1.15; 95% CI, 0.90–1.48; P = .27).ConclusionsThese results acquired during a follow-up of approximately 7 years (which included a median of less than 1.5 years of treatment) do not support the hypothesis that celecoxib or naproxen prevent AD in adults with a family history of dementia.     

Polymorphism of PRNP codons in the normal Icelandic population

OBJECTIVES: Polymorphisms in the prion protein gene in humans influence susceptibility to, and phenotype of, prion diseases. Methionine-methionine (MM) homozygosity at codon 129 is a risk factor for sporadic Creutzfeldt-Jakob disease (CJD). Polymorphism at codon 117 and changes in the octapeptide repeat region have been associated with genetic CJD. Knowledge of genetic background in normal populations may contribute to better understanding of prion diseases. MATERIALS AND METHODS: Polymorphism at codon 129, codon 117 and deletions of octapetide repeats were studied in 208 healthy blood donors of both genders and of different age. RESULTS: Polymorphism at codon 129 was: MM 46.6%, methionine-valine 44.7%, valine-valine 8.7%. Polymorphism at codon 117 was observed in 4.8%. Deletions of octapeptide repeats were not detected. There were no gender or age differences in the distribution of codon 129 polymorphism. The frequency of codon 129 polymorphisms was, with one exception, not significantly different from that observed elsewhere in Europe.     

Addressing population aging and Alzheimer's disease through the Australian Imaging Biomarkers and Lifestyle study: Collaboration with the Alzheimer's Disease Neuroimaging Initiative

The Australian Imaging Biomarkers and Lifestyle (AIBL) study is a longitudinal study of 1112 volunteers from healthy, mild cognitive impairment, and Alzheimer's disease (AD) populations who can be assessed and followed up for prospective research into aging and AD. AIBL aims to improve understanding of the pathogenesis, early clinical manifestation, and diagnosis of AD, and identify diet and lifestyle factors that influence the development of AD. For AIBL, the magnetic resonance imaging parameters of Alzheimer's Disease Neuroimaging Initiative (ADNI) were adopted and the Pittsuburgh compound B (¹¹C-PiB) positron emission tomography (PET) acquisition and neuropsychological tests were designed to permit comparison and pooling with ADNI data. Differences to ADNI include assessment every 18-months, imaging in 25% (magnetic resonance imaging, ¹¹C-PiB PET but no fluorodeoxyglucose PET), more comprehensive neuropsychological testing, and detailed collection of diet and lifestyle data. AIBL has completed the first 18-month follow-up and is making imaging and clinical data available through the ADNI website. Cross-sectional analysis of baseline data is revealing links between cognition, brain amyloid burden, structural brain changes, biomarkers, and lifestyle.     

Lack of seasonal mood change in the Icelandic population: results of a cross-sectional study

OBJECTIVE: The prevalence of seasonal affective disorder-as measured by the Seasonal Pattern Assessment Questionnaire-has been found to be unexpectedly low among Icelanders. The aim of this cross-sectional study was to measure seasonal variations in the prevalence of anxiety and depression among Icelanders assessed with the Hospital Anxiety and Depression Questionnaire. METHOD: Four 1, 000-person cohorts, age 20-70 years, selected at random from the Icelandic National Register, were sent the Hospital Anxiety and Depression Scale by mail in either January, April, July, or October. Only responses from the 4-week period after each mailing were considered in the subsequent analysis. RESULTS: The mean anxiety and depression scores in winter were not higher than those in summer for either sex. There was no significant difference between winter and summer in rates of actual or borderline cases of anxiety or depression or for the two categories combined. CONCLUSIONS: This lack of seasonality in anxiety and depression is in sharp contrast to findings from similar cross-sectional studies and may reflect the low propensity for seasonal affective disorder that has been described in the Icelandic population.