ASSOCIATION WITH REDUCED MORTALITY USING CHOLINESTERASE INHIBITORS IN PATIENTS WITH DEMENTIA: DATA FROM SVEDEM, THE SWEDISH DEMENTIA REGISTRY

Abstract

Recent studies have shown that cholinesterase inhibitors (ChEIs) associate with a reduced risk of death among patients with mild-to-moderate Alzheimer's disease, but it is not known whether the associations exist for other types of dementia or varies with stage of dementia. Registrants of Swedish dementia registry between 2008 and 2015 were linked to national death and drug registries. ChEIs treatment duration and dosages were obtained from complete collection of pharmacy dispensations in the national drug prescription registry (Läkemedelsregistret). The association between the use of ChEIs and death was examined by Cox proportional hazards model. Propensity score adjusted for age, sex, comorbidity and medications. Stages in the dementia course were defined using Mini Mental State Examination (MMSE) assessments. The cohort included 31,794 patients with a diagnoses of Alzheimer's dementia or mixed or vascular or Lewy body dementia. Of these, 8,901 had very mild dementia (MMSE score 25-30), 12,665with mild dementia (MMSE 20-24), and 10,228 with moderate to severe dementia (MMSE 0-19) at the start of ChEI treatment or dementia diagnosis. Mean age was 79±7.6 years and 59% was female. The proportions of ChEIs treatment were 83%, 62%, 16% and 87% among the patients with Alzheimer's, mixed, vascular and Lewy body dementia separately. During an average of 3.2 (range 0.1-9) years of follow up, 12,850 (40%) of cases died. After adjustment for age, sex, comorbidity and medications, ChEIs users had a 22% lower risk of death (adjusted hazard ratio [HR], 0.78; 95% confidence interval, 0.73-0.84) in Alzheimer's dementia compared with non-users. Effect sizes were similar in mixed [0.78 (0.72-0.83)] and vascular dementia [0.76 (0.69-0.84)], but not in Lewy body dementia [0.93 (0.71-1.22)]. ChEIs users also associated with lower risk of death in patients with very mild [0.71(0.65-0.76)], mild [0.75 (0.72-0.79)] and moderate to severe dementia stages [0.80 (0.75-0.85)] separately. There was also a graded association between cumulative exposure to ChEIs and death. Propensity score matched analyses showed similar results. Initiation of ChEIs therapy and cumulative ChEIs exposure are associated with decreased risk of mortality in Alzheimer's, mixed and vascular dementia patients, irrespective of dementia stage.