Temporal Quantification of Alzheimer's Disease Severity: 'Time Index' Model

Abstract

A fundamental issue in the clinical and neuropathological assessment of Alzheimer''s disease patients is quantification of dementia severity progression. Several methods have been advanced for the purpose of staging dementia with various sensitivities at different phases of the disease, but no mathematical function has been developed to link these measures to a physical continuum. Using a dynamic method for quantifying illness severity, change in severity over time was referenced to a cumulative temporal index, a physical dimension. Data from 33 patients with probable Alzheimer''s disease with at least 2 successive assessments on three 50-point scales measuring cognitive, behavioral, and daily living skills were used to determine rate of change. ''Fuzzy-logic'' smoothing of the data, integration over time, and least-squares regression were used to derive a cubic polynomial function to calculate a severity measure in which ''days of illness'' was estimated from the severity score. This method can be used to improve the comparability of performance across various mental status tests, and to link measures of very early phases of preclinical dementia and late profound dementia phases. This method also provides a description of an ''average'' time course for any population from which the index is derived.

The Not So ‘Mighty Chondrion’: Emergence of Renal Diseases due to Mitochondrial Dysfunction

“…Experimentally, exposing rat proximal tubular cells to cystine causes a decrease in solute reabsorption. This is associated with a fall in ATP levels and oxygen consumption, and more detailed analysis suggests inhibition of complex I (see figure 2) in the mitochondrial respiratory chain [25]. More recent work on primary cultures of human proximal tubular cells derived from urine has demonstrated that although mitochondria in cystinosis appear to function normally under baseline conditions, the levels of the important intracellular antioxidant agent glutathione are reduced.…”

Modeling the time-course of Alzheimer dementia

“…By systematic combination, these multiple scales provide a 150-point dynamic range. GCS values were then translated into TI units [1]. Using TI units, the repeated measures over time clearly demonstrate the devastating progression of AD (Fig.…”

The Stages of Alzheimer’s Disease: A Reappraisal

“…Ashford et al [19], for example, note that among the range of patients they tested, there was a close correlation between the MMSE and the time-index form of assessment, such that the MMSE could explain 90% of the variance of the latter. Each such scale could also be used to define stages that would perform comparably to both the GDS and the MMSE staging.…”

“…The issue of more meaningful quantification of rate of decline has been discussed in depth by Ashford et al [19]. In this study they developed a 'time-index' model of severity of AD, thus also an interval scale.…”

“…Ashford et al [19] emphasize the necessity of testing the entire range of AD pathology to obtain a nonbiased measurement of duration in any stage of disease. Such a task can very likely only be accomplished by sampling patients at the time of diagnosis of AD with regular and frequent assessment up to the time of death.…”