Associations of Alzheimer's disease with inpatient hospital costs and with quality-adjusted life years: Evidence from conventional and Mendelian randomization analyses in the UK Biobank

BACKGROUNDAlzheimers disease and other dementias are progressive neurodegenerative disorders with profound impacts on cognitive function. There is a shortage of economic evidence relating to the impact Alzheimers disease on healthcare costs and quality-adjusted life-years (QALYs). METHODSWe employed two study designs to model the association between Alzheimers disease and healthcare costs and QALYs. We first estimated conventional multivariable models of the association between Alzheimers disease and these core economic outcomes. However, these types of model may be confounded by diseases, processes, or traits that independently affect Alzheimers disease and either or both of healthcare costs and QALYs. We therefore also explored a complementary approach using germline genetic variation as instrumental variables in a Mendelian randomization analysis. We used single nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies of Alzheimers disease as instruments. We studied outcome data on inpatient hospital costs and QALYs in the UK Biobank cohort. RESULTSData from up to 310,838 individuals were analyzed. N=55 cases of Alzheimers disease were reported at or before recruitment into UK Biobank. A further N=284 incident cases were identified over follow-up. Multivariable observational analysis of the prevalent cases suggested significant impacts on costs ({pound}1,140 in cases, 95% Confidence Interval (CI): {pound}825 to {pound}1,456) and QALYs (-25%, 95% CI: -28% to -21%). Mendelian randomization estimates were very imprecise for costs ({pound}3,082, 95% CI: -{pound}7,183 to {pound}13,348) and QALYs (-32%, 95% CI: -149% to 85%), likely due to the small proportion of variance (0.9%) explained in Alzheimers disease status by the most predictive set of SNPs. IMPLICATIONSConventional multivariable models suggested important impacts of Alzheimers disease on inpatient hospital costs and QALYs, although this finding was based on very few cases which may have included instances of early-onset dementia. Mendelian randomization was very imprecise. Larger GWAS of clinical cases, improved understanding of the architecture of the disease, and the follow-up of cohorts until old age and death will help overcome these challenges.