Progression of Alzheimer's disease as measured by Clinical Dementia Rating Sum of Boxes scores

Background: This study examined rates of dementia progression as ascertained by the Clinical Dementia Rating Sum of Boxes (CDR-SB) for symptomatic Alzheimer's disease (sAD), and assessed participant characteristics as predictors of CDR-SB progression. Methods: Participants (n = 792) were enrolled in longitudinal studies at an Alzheimer's Disease Research Center, received a diagnosis of sAD with a global CDR of 0.5 (n = 466) or 1 (n = 326), and had at least one follow-up assessment. Progression in CDR-SB over time as a function of baseline global CDR was examined. Results: A longitudinal increase (P <.0001) in CDR-SB was observed. The annual rate of change in CDR-SB scores was 1.43 (standard error [SE] = 0.05) in the CDR 0.5 sample and 1.91 (SE = 0.07) in the CDR 1 sample. For participants followed from the beginning of the CDR stage, time to progression to a higher global CDR was longer for individuals who were CDR 0.5 (3.75 years; 95% confidence interval [CI]: 3.18-4.33) than those who were CDR 1 at baseline (2.98 years; 95% CI: 2.75-3.22). In the total CDR 0.5 sample, the significant predictors of progression to the next global CDR stage (P <.01) were age at first sAD diagnosis and apolipoprotein E4 genotype. Conclusions: The study findings are relevant to sAD clinical trial design and accurate, reliable ascertainment of the effect of disease-modifying treatments.