APOE and obesity due to melanocortin 4 receptor deficiency: In this study, we took advantage of the large sample size of UK Biobank to (1) evaluate the individual and joint associations of walking pace and handgrip strength with the risk of new-onset dementia, and the major subtypes of dementia (AD and vascular dementia), and (2) to further examine the possible modifying effects of age, APOE ε4 dosage, family history of dementia, and dementia modifiable risk factors including obesity, physical activity, hypertension, depression, and diabetes on the walking pace and dementia associations.