RESUMEN
Survival analysis techniques using Cox proportional hazards regressions with time-dependent covariates, life table survival plots, and Kaplan-Meier estimates were used to evaluate the effect of long-term tacrine hydrochloride (Cognex) treatment on nursing home placement (NHP) and mortality in patients with Alzheimer's disease. Patients with probable Alzheimer's disease (NINCDS criteria) who were randomized in a 30-week double-blind, placebo-controlled, parallel-group, high-dose study of tacrine (1) were subsequently allowed to receive long-term, open-label treatment during which they could receive doses up to 160 mg/day. Using last tacrine dose, the analyses demonstrated a dose-response relationship where patients on higher tacrine doses were less likely to enter a nursing home or die than patients on lower doses. The Cox proportional hazards regression approach with time-dependent covariates is also compared to logistic regression, which looks only at the crude proportions of patients having the event. Since logistic regression does not allow for the use of time-dependent covariates, it provides somewhat less conservative estimates of the magnitude of the treatment effect.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/mortalidad , Casas de Salud , Parasimpaticomiméticos/uso terapéutico , Análisis de Supervivencia , Tacrina/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Estudios de Evaluación como Asunto , Estudios de Seguimiento , Humanos , Placebos , Modelos de Riesgos ProporcionalesRESUMEN
Factor analysis methodology applied to Alzheimer's Disease Assessment Scale (ADAS) subtest profiles for patients in two large-scale clinical trials of the antidementia drug tacrine yielded three oblique factors interpreted as dysfunctions in memory, language, and praxis. The factor structures confirmed reliable assessment of primary dimensions of cognitive impairment in Alzheimer's disease that the original authors of the ADAS proposed to measure and that correspond well to that of the only previously reported factor analysis of the ADAS-COG. The presence of a strong general factor, supported by stable correlations among the oblique primary factors, justifies the recommendation to continue reliance on the ADAS-COG total score as a primary outcome measure in clinical trials, whereas the factor scores are recommended for evaluation of differential treatment effects on more specific aspects of the general cognitive decline. The stability of correlations across time appears to satisfy a primary requirement for application of repeated measures ANOVA to ADAS-COG total score and factor scores in longitudinal clinical trials.