In this cohort study including 465 929 participants from the UK Biobank, 4 widely-used risk scores (Cardiovascular Risk Factors, Ageing and Dementia [CAIDE-Clinical], CAIDE–APOE-supplemented, Brief Dementia Screening Indicator [BDSI], and Australian National University Alzheimer Disease Risk Index [ANU-ADRI]) missed 84% to 91% of participants with incident dementia when the threshold for a positive test result was calibrated to achieve a 5% false-positive rate, and to detect at least half of participants with incident dementia, the ratio of true to false positives exceeded 1 to 66. This evidence concerns the gene APOE and dementia.