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 (£1,140 in cases, 95% Confidence Interval (CI): £825 to £1,456) and QALYs (−25%, 95% CI: -28% to -21%). Mendelian randomization estimates were very imprecise for costs (£3,082, 95% CI: -£7,183 to £13,348) 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding statement: P.D. received support from NIHR ARCs Dementia Capacity Building Post-Doctoral Training Scheme (DEM-COMM). E.A. is supported by a UKRI Future Leaders Fellowship (MR/W011581/1) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Our principal data source was the prospective UK Biobank cohort (North west Haydock research ethics approval reference 11/NW/0382) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The derived cost and QALY variables will be archived with UK Biobank as returned variables and will be made available to individuals who obtain the necessary permissions from the study`s data access committee. Analysis code is available here: .