An association between weight loss and Alzheimer’s disease has been established in the general population but little information is available regarding this association in people with intellectual disabilities. A 4-year longitudinal study of adults with Down syndrome with and without Alzheimer’s disease was undertaken. Age-associated weight loss was seen in virtually all older adults with Down syndrome. A significant association between weight loss and Alzheimer’s disease was found for older adults with Down syndrome. This study highlights important research and clinical issues regarding weight loss and nutrition in Down syndrome adults with dementia.