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

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.

1992 ◽  
Vol 11 (4) ◽  
pp. 111-124 ◽  
Author(s):  
Lena Borell ◽  
Per-Olof Sandman ◽  
Gary Kielhofner

Author(s):  
A.M. Wessels ◽  
S.A. Dowsett ◽  
J.R. Sims

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.


2021 ◽  
Author(s):  
Nana Han ◽  
◽  
Yang Fang ◽  
Guozhen Zhao ◽  
Bo Ji

Review question / Objective: According to the current randomized clinical trials (RCT) of acupuncture therapy for Alzheimer's disease (AD), to evaluate their methodology, the quality of evidence and the report are evaluated and summarize evidence of important outcomes of randomized clinical trials. We aim to provide accurate clinical decision-making for acupuncture treatment of Alzheimer's disease. Condition being studied: According to the current randomized clinical trials (RCT) of acupuncture therapy for Alzheimer's disease (AD), to evaluate their methodology, the quality of evidence and the report are evaluated and summarize evidence of important outcomes of randomized clinical trials. We aim to provide accurate clinical decision-making for acupuncture treatment of Alzheimer's disease.


2012 ◽  
Vol 153 (12) ◽  
pp. 461-466 ◽  
Author(s):  
Magdolna Pákáski ◽  
Gergely Drótos ◽  
Zoltán Janka ◽  
János Kálmán

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soo Hyun Cho ◽  
Sookyoung Woo ◽  
Changsoo Kim ◽  
Hee Jin Kim ◽  
Hyemin Jang ◽  
...  

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.


2020 ◽  
Author(s):  
ningyuan zhang ◽  
Xijun Zheng ◽  
Hongxia Liu ◽  
Qingshan Zheng ◽  
Lujin Li

Abstract Background Our objective was to develop a disease progression model for cognitive decline in Alzheimer’s disease (AD) and to determine whether disease progression of AD is related to the year of publication, add-on trial design, and geographical regions. Methods Placebo-controlled randomized AD clinical trials were systemically searched in public databases. Longitudinal placebo response (mean change from baseline in the cognitive subscale of the Alzheimer’s Disease Assessment Scale [ADAS-cog]) and the corresponding demographic information were extracted to establish a disease progression model. Covariate screening and subgroup analyses were performed to identify potential factors affecting the disease progression rate. Results A total of 142 publications (148 trials) were included in this model-based meta-analysis. The typical disease progression rate was 5.82 points per year. The baseline ADAS-cog score was included in the final model using an inverse-U type function. Age was found to be negatively correlated with disease progression rate. After correcting the baseline ADAS-cog score and the age effect, no significant difference in disease progression rate was found between trials published before and after 2008, and between trials using add-on design and those that did not use add-on design. However, a significant difference was found among different trial regions. Trials in East Asian countries showed the slowest decline rate and the largest placebo effect. Conclusions Our model successfully quantified AD disease progression by integrating baseline ADAS-cog score and age as important predictors. These factors and geographic location should be considered when optimizing future trial designs and conducting indirect comparisons of clinical outcomes.


Author(s):  
F. McDougall ◽  
C. Edgar ◽  
M. Mertes ◽  
P. Delmar ◽  
P. Fontoura ◽  
...  

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.


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