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

BACKGROUND Alzheimer`s 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 Alzheimer`s disease on healthcare costs and quality-adjusted life-years (QALYs). METHODS. We employed two study designs to model the association between Alzheimer`s disease and healthcare costs and QALYs. We first estimated conventional multivariable models of the association between Alzheimer`s disease and these core economic outcomes. However, these types of model may be confounded by diseases, processes, or traits that independently affect Alzheimer`s 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 Alzheimer`s disease as instruments. We studied outcome data on inpatient hospital costs and QALYs in the UK Biobank cohort. RESULTS Data from up to 310,838 individuals were analyzed. N=55 cases of Alzheimer`s 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 (GBP1,140 in cases, 95% Confidence Interval (CI): GBP825 to GBP1,456) and QALYs (-25%, 95% CI: -28% to -21%). Mendelian randomization estimates were very imprecise for costs (GBP3,082, 95% CI: -GBP7,183 to GBP13,348) and QALYs (-32%, 95% CI: -149% to 85%), likely due to the small proportion of variance (0.9%) explained in Alzheimer`s disease status by the most predictive set of SNPs. IMPLICATIONS Conventional multivariable models suggested important impacts of Alzheimer`s 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.