Effects of cognitive changes on survival for persons with Alzheimer\u27s Disease - joint modeling analysis

This study assessed three associations simultaneously: the association of baseline disease characteristics on survival, the association of disease progression on survival and lastly the association of baseline disease characteristics on progression among persons with Alzheimer’s Disease by modeling the longitudinal cognitive scores and survival process simultaneously. We hypothesized that cognitive changes over time would have an effect on the survival experience for this disease and that these two processes are correlated. The study design was a prospective cohort of community-dwelling patients seen in an academic memory disorders research center in Houston, Texas who were diagnosed with probable Alzheimer’s disease at baseline and had at least one comprehensive follow-up visit until loss due to death, drop off from the study or who remained in the study through January 31, 2014. Vital statuses for all study participants were ascertained by the Social Security Administration Death Master File prior to January 31, 2014. Censoring (right) was chosen for subjects who did not experience the event (death) when the study terminated on January 31, 2014. Individual-level covariates were obtained at the initial visit. Cognitive and functional measurements were collected at each annual visit. Length of follow-up in years at each study visit was calculated as duration in time from the initial visit. A joint modeling technique was applied to the data by specifying the shared random effects of the survival model and the mixed- effects model. We found that gender, disease severity at time of diagnosis, rate of progression at time of diagnosis measured by a simple calculated variable based on a global cognitive score and an estimated duration of illness had significant effects not only on the repeatedly measured Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB) but also on the mean survival time. We found that there was a correlation, which depended on the follow-up (time elapsed since initial visit), between the longitudinal CDR Sum of Boxes and the log of survival time. By year 5 of follow-up this correlation coefficient reached -0.84. These findings suggested that the survival time of persons with Alzheimer’s disease were affected by the progression of their cognitive/functional performance in the presence of other risk factor