BACKGROUND: The economic burden associated with inefficiencies and waste in the US healthcare system ranges from $760 to $935 billion annually.1 Certain categories of healthcare inefficiencies, such as missed prevention opportunities, leave a significant impact on society from both health and economic perspectives.2 In the context of health economics, prevention of a chronic condition includes opportunities to slow disease progression. In patients with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or AD dementia, the costs of potential missed prevention opportunities correspond to the economic burden associated with progression to later stages of AD.
OBJECTIVES: To estimate the economic burden of daily transitions to later stages of AD in the US.
METHODS: A comprehensive literature review was conducted to estimate the number of patients transitioning to the next stage of AD severity and the associated costs. Using a funnel-based approach, we first estimated the number of biomarker-positive MCI due to AD and AD dementia cases in the US among those ≥50 years old. Starting with the Centers for Disease Control and Prevention WONDER data in the population ≥50 years old, we applied age- and race/ethnicity-stratified estimates of the prevalence of all-cause MCI or AD dementia clinical syndrome from a recent study in individuals ≥65 years old.3 In those <65 years old, literature on MCI prevalence was limited and estimates were derived from 2 additional sources.4,5 Likewise in AD, estimates in individuals <65 years old were sourced from the Alzheimer’s Association.6 We then estimated the number of all-cause MCI cases that would be clinically attributable to AD7 and the proportion of AD cases by dementia severity (mild, moderate, severe).8 Finally, we estimated the number of these cases likely to be amyloid-positive using results from the Amyloid Biomarker Study.9 Annual transition probabilities from the National Alzheimer’s Coordinating Center10 were applied to the amyloid-positive case estimates, and these counts were used to approximate the number of daily transitions from each stage to the next advanced stage of AD severity. Next, we identified direct medical, nonmedical, and unpaid caregiving costs in the US by disease stage. The GERAS-US study11 was selected as the most appropriate source of costs in patients with MCI due to AD and mild AD dementia. Costs for moderate and severe AD dementia were estimated using between-stage ratios from an observational study.12 Both studies relied on the Resource Utilization in Dementia questionnaire13 and US-specific unit costs to estimate care costs. For the proportion of patients in institutional settings,14 direct medical costs were assumed to equal costs in the community, direct nonmedical costs were obtained from the Genworth Cost of Care Survey15,16 and unpaid caregiving costs were set to 44% of those in the community based on results from the What Matters Most study.17 Costs were inflated to 2021 US dollars where required.18,19
RESULTS: The economic burden associated with progression of AD was estimated using the number of patients who transition from one stage to the next each day. Progression of 5792 patients from MCI due to AD to mild AD dementia per day accounted for the highest burden with an incremental daily cost of $323,891 (approximately $118 million per year). Likewise, the burden associated with daily transitions from mild to moderate AD dementia (n=2308) and from moderate to severe AD dementia (n=1438) were $88,747 and $143,923, respectively. Cost of progression to more advanced stages of AD dementia might be even higher when including transitions of >1 stage annually or when accounting for the potential impact of AD caregiving on a caregiver’s direct medical costs.11 Results should be considered in the context of limitations of the available data.
CONCLUSION: The estimated daily impact of disease progression to later stages of AD on a population-level in the US is associated with significant economic burden that represents potential missed prevention opportunities. Any timely intervention that slows the progression could substantially mitigate the economic and health burden of AD in the US.
