APPLICATION OF A GROWTH CURVE APPROACH TO MODELING THE PROGRESSION OFALZHEIMERS-DISEASE

Background. Studies using clinical measures to track AD progression of ten assume linear declines over the entire course of the disease. whic h may not be justified. The objective of this study was to model chang e in measures of the clinical severity of Alzheimer's disease (AD) ove r time. Methods. We developed a method to apply growth curve models to prospective data and characterize AD patients' functional change over time. Data from the modified Mini-Mental State Examination (mMMSE) an d measures of basic and instrumental ADL. administered semiannually fo r up to 5 years to 236 patients with probable AD, were modeled. Result s. The rate of decline in mMMS scores per 6-month interval gradually i ncreased as scores dropped from the maximum of 57 to 20. The rate of d ecline then decreased as scores approached 0, resulting in an inverse ''S'' curve. The rate of increase in instrumental ADL scores per inter val attenuated as the scores increased. while that for basic ADL score s across intervals was constant. Conclusions. Differences in the patte rn of progression of the three measures is in pan a function of their psychometric properties. The progression curves may also reflect conte nt-specific features of the instruments. Superimposition oi. the model ed decline in these three content areas suggests a hypothetical model of the relative timing of cognitive and and functional changes in AD.