Predictors of mortality in patients with different apolipoprotein E genotypes—a 20-year follow-up of Alzheimer’s disease.

Background: To identify apolipoprotein E (APOE)-specific factors that may predict life expectancy after a diagnosis of Alzheimer’s disease (AD). Method: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, clinical-practice-based, multicentre study that includes 999 participants diagnosed with mild-to-moderate AD at the start of cholinesterase inhibitor (ChEI) therapy (time of diagnosis). Cognition and activities of daily living (ADL) were evaluated at baseline and semi-annually over 3 years, and the date of death was recorded. Result: After 20 years, 309/320 (97%) of the APOE non-ε4-carriers, 497/528 (94%) of the one-ε4-carriers, and 140/151 (93%) of the two-ε4-carriers had died (p=0.154). In the multivariate Cox regression models, risk factors for shorter lifespan in all patients were older age, lower cognitive ability at baseline, and faster cognitive decline/year. Moreover, a higher ChEI dose and/or longer treatment duration predicted increased survival. In APOE non-ε4-carriers, male sex, antidiabetic or antihypertensive/cardiac therapy, worse basic ADL at baseline, and faster instrumental ADL progression were observed to decrease life expectancy. In one-ε4-carriers, male sex, antihypertensive/cardiac therapy, and faster basic ADL deterioration predicted shorter survival. In two-ε4-carriers, antidiabetic use and longer AD duration were risk factors for decreased lifespan. Conclusion: Common risk factors for death, such as male sex, cardiovascular disorders, and functional impairment, were demonstrated in non-ε4-carriers and one-ε4-carriers, but not in two-ε4-carriers. The consequences of dementia, such as cognitive decline and duration of AD, may have a greater impact on survival in APOE two-ε4-carriers. Optimal ChEI treatment had positive effects in all patients irrespective of APOE genotype.