OBJECTIVES: It is unclear if slowing disease progression with disease-modifying treatment (DMT) for Alzheimer’s disease (AD) also leads to a reduction in mortality. The study aims to determine the overall and cause-specific mortality of AD in relation to disease severity and the impact of different mortality assumptions on the cost-effectiveness of a hypothetical DMT.

METHODS: Data were derived from the Swedish Dementia Registry (N=41,101). The overall and cause-specific mortality were estimated by survival analysis and multinomial logistic regression. A state-transition microsimulation model was constructed to assess the cost-effectiveness of DMT using routine care as a comparator. Three hypothetical scenarios were explored: (1) slowing progression with DMT leads to corresponding reduction of mortality, (2) no effect of DMT on mortality, (3) slowing disease progression only affects AD-related mortality.

RESULTS: Hazard ratio (HR) of death was increased with age, disease severity, and in male patients (p<0.001). After adjusting for age, gender, BMI and number of medications, the mortality from cardiovascular, dementia, gastrointestinal, respiratory, infectious causes and external injury were increased with disease severity (p<0.001). DMT was projected to increase survival to 0.34 years in scenario 1 and 0.14 years in scenario 3. At an annual price of 274,000 SEK (1USD=8.55SEK) for DMT, the costs were estimated to increase by 1,024,585 SEK, 872,398 SEK and 934,501 SEK and QALYs by 0.41, 0.23 and 0.30 for scenario 1, 2 and 3 respectively. The incremental cost-effectiveness ratio (ICER) was the highest in scenario 2. When reducing the DMT price to 50,000 SEK, the results were contradictory, with cost-saving in scenario 2.

CONCLUSIONS: Delaying disease progression might also lead to reducing mortality from all causes. With a high price of DMT, not having a mortality effect results in higher ICER than having an indirect mortality effect. The cost and mortality effect have a major influence on the cost-effectiveness of DMT.