scholarly journals Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia

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.

2019 ◽  
Author(s):  
Soo Hyun Cho ◽  
Sookyoung Woo ◽  
Changsoo Kim ◽  
Hee Jin Kim ◽  
Hyemin Jang ◽  
...  

Abstract Background: To 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. Methods: We used longitudinal data from 127 participants with preclinical AD and 309 participants with mild cognitive impairments (MCI) due to AD from the Alzheimer’s Disease Neuroimaging Initiative. In order 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 according to the follow-up time for each cohort, determined the time point at which the estimated scores of ADAS-cog 13 for the two cohorts first overlapped, and shifted the ADAS-cog 13 scores for the latter cohort at this time point to connect the two cohorts and to combine the data into a single unified progression course. Results: The estimated years for progression from the median ADAS-cog 13 score in the preclinical AD cohort (9.3 points) to the median ADAS-cog 13 score at the time of progression in the participants who progressed from preclinical AD to MCI due to AD (16.0 points) was 7.8 years. The estimated years for progression from preclinical AD to the median ADAS-cog 13 score at the time of progression in those who progressed from MCI to due AD to AD dementia (26.8 points) was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in female APOE ε4 carriers and most slowly in male APOE ε4 non-carriers ( p < 0.001). Conclusion: 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.


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 79 (1) ◽  
pp. 225-235
Author(s):  
Maya Arvidsson Rådestig ◽  
Johan Skoog ◽  
Henrik Zetterberg ◽  
Jürgen Kern ◽  
Anna Zettergren ◽  
...  

Background: We have previously shown that older adults with preclinical Alzheimer’s disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. Objective: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. Methods: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Results: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Conclusion: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.


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):  
T.M. Solomon ◽  
J.M. Barbone ◽  
H.T. Feaster ◽  
D.S. Miller ◽  
G.B. deBros ◽  
...  

The Alzheimer’s Disease Assessment Scale (ADAS-Cog) has become the de facto gold-standard for assessing the efficacy of putative anti-dementia treatments. There has been an increasing interest in providing greater standardization, automation, and administration consistency to the scale. Recently, electronic versions of the ADAS-Cog (eADAS-Cog) have been utilized in clinical trials and demonstrated significant reductions in frequency of rater error as compared to paper. In order to establish validity of the electronic version (eADAS-Cog), 20 subjects who had received a diagnosis of probable Alzheimer’s disease (AD) at a private US Memory Clinic completed a single-center, randomized, counterbalanced, prospective trial comparing a version of the eADAS-Cog to the standard paper scale. Interclass Correlation Coefficient on total scores and Kappa analysis on domain scores yielded high agreement (0.88 – 0.99). Effects of order and mode of administration on ADAS-Cog total scores did not demonstrate a significant main effect. Overall, this study establishes adequate concurrent validity between the ADAS-Cog and eADAS-Cog among an adult population with diagnosed AD.


2017 ◽  
Vol 60 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Sonia Ben Jemaa ◽  
Neila Attia Romdhane ◽  
Amel Bahri-Mrabet ◽  
Adel Jendli ◽  
Didier Le Gall ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document