PREDICTORS OF MORTALITY IN EARLY- VERSUS LATE-ONSET ALZHEIMER’S DISEASE: AN 18-YEAR FOLLOW-UP

Abstract

Background: Few studies have focused on predictors of survival in patients with early-onset Alzheimer’s disease (EOAD) compared with late-onset Alzheimer’s disease (LOAD). We aimed to investigate the effect of genetic, sociodemographic, and clinical factors on mortality in the two groups.Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for longitudinal assessment of cholinesterase inhibitor (ChEI) therapy in clinical practice that includes 1,021 participants diagnosed with mild-to-moderate Alzheimer’s disease (AD) (Mini-Mental State Examination score, 10–26) at the start of ChEI treatment. Of these, 143 were defined as having EOAD (onset =65 years), and four missing age-at-onset; thus, 1,017 patients were included. Cox proportional hazards regression was used to determine characteristics that affected life expectancy: sex, apolipoprotein E genotype, solitary-living, duration of AD, age at baseline, years of education, specific concomitant medications, cognition (Alzheimer’s Disease Assessment Scale–cognitive subscale [ADAS-cog]) and activities of daily living (ADL) (Instrumental Activities of Daily Living scale [IADL] and Physical Self-Maintenance Scale [PSMS]) at baseline, and their rates of decline.Results: After 18 years of follow-up, 115 (80%) of the EOAD and 797 (91%) of the LOAD patients had died (p<0.001). In EOAD, males living alone, hazard ratio (95% confidence interval), 2.71 (1.18–6.22), p=0.019, lower IADL capacity at baseline, 1.07 (1.02–1.11), p=0.002, and faster rate of basic ADL deterioration/year 0.87 (0.77–0.98), p=0.026 independently predicted shorter survival. In LOAD, males of any living status 1.64 (1.41–1.92), p<0.001, older age at baseline, 1.04 (1.03–1.06), p<0.001, use of antihypertensive/cardiac therapy, 1.26 (1.09–1.47), p=0.002, use of antidiabetics, 1.51 (1.06–2.14), p=0.021, lower cognitive ability 1.02 (1.01–1.03), p<0.001 and worse basic ADL at baseline 1.05 (1.02–1.09), p=0.004, and faster rates of progression/year (ADAS-cog, 0.99 (0.98–0.99), p=0.004, PSMS, 0.92 (0.89–0.95), p<0.001) independently predicted shorter survival.Conclusions: Predictors of mortality differed between age groups. More impaired IADL, but not cognitive performance, was a risk factor for worse prognosis in EOAD. Solitary-living younger males exhibited nearly a threefold risk of death compared with corresponding males living with a family. In LOAD, demographic factors, cardiovascular comorbidities, and cognitive status had a significant impact on survival. (Less)