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. 2011 Nov;7(11):e1002251.
doi: 10.1371/journal.pcbi.1002251. Epub 2011 Nov 3.

High degree of heterogeneity in Alzheimer's disease progression patterns

Natalia L Komarova  1 , Craig J Thalhauser
Affiliations

High degree of heterogeneity in Alzheimer's disease progression patterns

Natalia L Komarova et al. PLoS Comput Biol. 2011 Nov.

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The calculated cumulative probability distribution functions for GDS/FAST stage durations.
Figure 2
Figure 2. The mean values and standard deviations calculated for GDS/FAST stages 4–6.
The black bars represent GDS stages, and the gray bars – FAST stages. The mean stage values reported in are presented by dashed horizontal lines.
Figure 3
Figure 3. Some statistics of the dataset.
(a) A histogram showing the number of records per patient. (b) A histogram showing patient inter-visit times.
See this image and copyright information in PMC

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