Abstract
IntroductionThis longitudinal study examined multiple factors that influence survival in a cohort of Alzheimer patients followed over two decades.MethodsTime to death after symptom onset was determined in 641 probable AD patients who were evaluated annually until death or loss to follow-up, and information was entered into a longitudinal database. Date of death was available for everyone including those eventually lost. Baseline variables included age, sex, race, disease severity, a calculated index of rate of initial cognitive decline from symptom onset to cohort entry (pre-progression rate or PPR), years of education, and medical comorbidities (diabetes, hypertension, hyperlipidemia, coronary disease, cerebrovascular disease). Multivariable Cox proportional hazard regression analysis was used to analyze the baseline and/or time dependent association in Mini-mental Status Exam (MMSE) severity, Physical Self Maintenance Scale (PSMS), Persistency Index (PI) of exposure to antipsychotic and antidementia drugs, and psychotic symptoms (hallucinations, delusions) with mortality.ResultsBaseline covariates significantly associated with increased survival were younger age (p = .0016), female sex (p = .0001), and a slower PPR (p < .0001). Overall disease severity at baseline, medical comorbidities, and education did not influence time to death. Time-dependent changes in antipsychotic drug use, development of psychotic symptoms, antidementia drug use, and observed MMSE change were not predictive. In the final model the only time-dependent covariate that significantly decreased survival was worsening of functional ability on the PSMS (hazard ratio = 1.10; CI: 1.07-1.11).ConclusionsIn this large AD cohort survival is influenced by age, sex, and the development of functional disability during follow-up. The most important predictor of mortality was a faster rate of cognitive decline at the initial patient visit (PPR). The currently available antidementia drugs do not prolong survival in Alzheimer patients.
Highlights
This longitudinal study examined multiple factors that influence survival in a cohort of Alzheimer patients followed over two decades
Median survival time among the 641 patients with probable Alzheimer’s disease (AD) following the onset of symptoms was 11.3 years (CI = 10.4 to 11.8), and there were 352 deaths
Increasing age, male gender, and faster rate of cognitive decline at baseline as measured by the pre-progression rate (PPR) category - hazard ratios were 0.45, 0.75, and 0.59, and 95% confidence interval (CI) were 0.30 to 0.66, 0.54 to 1.04, and 0.43 to 0.82, respectively - were significantly associated with increased risk of death (Table 2)
Summary
This longitudinal study examined multiple factors that influence survival in a cohort of Alzheimer patients followed over two decades. Several observational studies [11,12,13,14] found no relationship between the use of any antidementia drug regimen (cholinesterase inhibitor or memantine or both) and survival when users were compared with untreated patients. Two large cross-sectional studies that involved retrospective data analysis reported that the use of cholinesterase inhibitors versus no treatment significantly increased survival in nursing home patients. Both tacrine use [15] (hazard ratio = 0.76, confidence interval (CI) = 0.70 to 0.83) and donepezil use [16] (hazard ratio = 0.89, 95% CI = 0.83 to 0.95) were associated with significantly reduced mortality. This study evaluated a broad range of covariates suspected to influence survival and assessed the use of antidementia drugs in a time-dependent analysis
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call