Abstract
There have been several reports on the varying rates of progression among Alzheimer's Disease (AD) patients; however, there has been no quantitative study of the amount of heterogeneity in AD. Obtaining a reliable quantitative measure of AD progression rates and their variances among the patients for each stage of AD is essential for evaluating results of any clinical study. The Global Deterioration Scale (GDS) and Functional Assessment Staging procedure (FAST) characterize seven stages in the course of AD from normal aging to severe dementia. Each GDS/FAST stage has a published mean duration, but the variance is unknown. We use statistical analysis to reconstruct GDS/FAST stage durations in a cohort of 648 AD patients with an average follow-up time of 4.78 years. Calculations for GDS/FAST stages 4–6 reveal that the standard deviations for stage durations are comparable with their mean values, indicating the presence of large variations in the AD progression among patients. Such amount of heterogeneity in the course of progression of AD is consistent with the existence of several sub-groups of AD patients, which differ by their patterns of decline.
Highlights
The temporal progression of Alzheimer’s Disease (AD) shows a pattern of high variability, with patients transiting the stages of the disease having time-courses ranging from months to decades [1,2]
We quantify the amount of spread in Global Deterioration Scale (GDS)/Functional Assessment Staging procedure (FAST) stage durations
We arrive at an astonishing conclusion that the mean length of AD stages is comparable with their standard deviation! This means that individual courses of AD progression may differ very much from each other, and from the textbook mean values
Summary
The temporal progression of Alzheimer’s Disease (AD) shows a pattern of high variability, with patients transiting the stages of the disease having time-courses ranging from months to decades [1,2]. For any current and future progression-delaying drug, it is important to be able to establish whether and by how much it delays the deterioration caused by AD. To this end, it is necessary to have a reliable quantification of the heterogeneity of the disease. While a number of scales exist, GDS is one of the most widely used instruments to stage the course of AD. It measures cognitive, behavioral and functional impairment of patients. GDS has been shown to correlate with both behavioral measures, and anatomic brain changes [20]
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