Development and validation of a dementia risk score in the UK Biobank and Whitehall II cohorts

Abstract

Background: Current dementia risk scores have had limited success in consistently identifying at-risk individuals across different ages and geographical locations.

Objective: We aimed to develop and validate a novel dementia risk score for a midlife UK population, using two cohorts: the UK Biobank, and UK Whitehall II study.

Methods: We divided the UK Biobank cohort into a training (n=176 611, 80%) and test sample (n=44 151, 20%) and used the Whitehall II cohort (n=2934) for external validation. We used the Cox LASSO regression to select the strongest predictors of incident dementia from 28 candidate predictors and then developed the risk score using competing risk regression.

Findings: Our risk score, termed the UK Biobank Dementia Risk Score (UKBDRS), consisted of age, education, parental history of dementia, material deprivation, a history of diabetes, stroke, depression, hypertension, high cholesterol, household occupancy, and sex. The score had a strong discrimination accuracy in the UK Biobank test sample (area under the curve (AUC) 0.8, 95% CI 0.78 to 0.82) and in the Whitehall cohort (AUC 0.77, 95% CI 0.72 to 0.81). The UKBDRS also significantly outperformed three other widely used dementia risk scores originally developed in cohorts in Australia (the Australian National University Alzheimer's Disease Risk Index), Finland (the Cardiovascular Risk Factors, Ageing, and Dementia score), and the UK (Dementia Risk Score).

Clinical implications: Our risk score represents an easy-to-use tool to identify individuals at risk for dementia in the UK. Further research is required to determine the validity of this score in other populations.

Keywords: Adult psychiatry; Delirium & cognitive disorders; PSYCHIATRY.

Figure 1

Receiver-operating characteristic curves (ROC) for each risk score in the UKB test set. Sensitivity and specificity (plotted from 1 to 0) at varying thresholds to build and ROC curve for each risk score computed in the UKB test set. The highest performing score, as indicated by the greatest area under the curve, was the UKBDRS-APOE model, followed by the UKBDRS, age only, DRS, CAIDE, and ANU-ADRI. The UKBDRS-APOE performance is assessed in the subset of individuals with genotype information available. ANU-ADRI, Australian National University Alzheimer’s Disease Risk Index; CAIDE, Cardiovascular Risk Factors, Aging and Dementia; DRS, Dementia Risk Score; UKB, UK Biobank; UKBDRS, UK Biobank Dementia Risk Score; WHII, Whitehall II.