Various measures of progression predicting mortality in Alzheimer’s disease

Abstract

To determine factors that might influence life expectancy in Alzheimer's disease (AD) patients treated with cholinesterase inhibitors (ChEIs) in clinical practice, the present study used statistical models with different measures of AD progression. The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study to evaluate the use of long-term ChEI therapy. The SATS included 1,021 participants with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination (MMSE) score, 10–26) at the start of ChEI treatment. Cognitive ability, activities of daily living (ADL), and use of community-based services were evaluated semiannually over 3 years. If patients died, their date of death was recorded. After up to 16 years of follow-up, 841 patients (82%) were deceased. Rates of cognitive decline and deterioration of basic ADL, and increased use of home help services and adult day care were independent predictors of survival after AD diagnosis in a Cox regression model after controlling for sex, age, disease severity, and number of medications at baseline. Kaplan–Meier modeling showed that the mean (95% confidence interval) time from AD diagnosis to death decreased for participants with increased cognitive decline, from 7.1 (6.6–7.7) years (MMSE change/year, ≤0 points) to 5.1 (4.7–5.6) years (MMSE change/year, ≥5 points; P<0.001), and also decreased for patients with increased deterioration of basic ADL from 7.4 (6.7–8.0) years (Physical Self-Maintenance Scale (PSMS) change/year, ≤0 points) to 4.1 (3.2–4.9) years (PSMS change/year, ≥4 points; P<0.001). Time from diagnosis to death decreased for patients who increased their use of home help services, from 6.7 (6.2–7.2) years (no change) to 5.6 (4.8–6.3) years (>5 hours increase/week; P<0.001), and for those who increased their use of adult day care, from 6.7 (6.3–7.1) years (no change) to 5.8 (5.2–6.4) years (>2 days increase/week; P<0.001). Risk factors for shorter life expectancy were annual decrease of ≥3 MMSE points, ≥2 basic ADL points, or an increase of >2 hours of home help services/week or >1 day of adult day care/week. These figures can be used as prognostic tools for patient survival in AD.