Determinants of survival of patients with Alzheimer's disease: The role of disability and severity of cognitive impairment

This study focused on ascertaining whether there is an independent role of cognitive impairment and associated disability in the survival of patients with Alzheimer's disease. Survival of a cohort of 273 consecutive patients first diagnosed at Rho Hospital with Alzheimer's disease from 1990 to 1995 was analyzed by the Kaplan-Meier method and Cox's proportional hazard model. The risks of death were evaluated as hazard ratios (HR) from the coefficients of Cox regression, and 95% confidence intervals (95% CI) were calculated from the standard errors of these coefficients. The mean age of the cohort was 75 years with a mean duration of the disease of 2 years and a mean MMSE and IADL score of 12 and 2.3, respectively. After a median follow-up of 67 months there were 110 deaths; mortality was 9% after 1 year and 17 and 45% after 3 and 5 years from the first diagnosis. In univariate analysis, age, cognitive impairment, and severity of disability were significant predictors of survival. In particular, patients older than 80 years had a risk of death that was significantly increased two fold with respect to patients younger than 70 years (HR 2.0 95% CI 1.22-3.16). Subjects with a MMSE score lower than 5 had a two fold increased risk of death with respect to subjects with a MMSE score of 16 or higher (HR 2.0 95% CI 1.18-3.40). No difference in mortality was observed between patients with a MMSE score of 16 or higher and those who had scores from 6 to 15. Patients with a IADL score of two or lower had a risk of death of 2.2 (95% CI 1.45-3.40) relative to those with higher IADL scores. When a multivariable analysis was carried out considering MMSE and IADL scores, the degree of cognitive impairment was no longer a significant predictor of survival, whereas the severity of disability was still significantly associated with the risk of death (HR 2.0 95% CI 1.22-3.31 for patients with IADL scores of 2 or lower). The significance of degree of disability as a mortality predictor was conserved also when other variables (age, comorbility, education and sex) were considered. In conclusion, these results suggest that, at the time of first diagnosis, disability is crucial and even more relevant than cognitive impairment in predicting survival of patients with Alzheimer's disease.