Diagnosis of dementia in adults with intellectual disabilities requires documentation of clinically significant declines in memory and other cognitive skills, as well as changes in everyday and emotional functioning. To improve diagnostic accuracy in adults with Down syndrome, the authors examined conditions often associated with dementia, as well as tests useful for documentation of decline. Specific aims were to identify psychiatric disorders or medical conditions that increased the odds of a dementia diagnosis; to evaluate the sensitivity and specificity of widely used dementia scales; and to determine which tests, used singly or in combination, most accurately supported the presence of dementia. Participants were 78 adults with Down syndrome. Two methods based on a large test battery and one method based on clinical judgment were used to diagnose dementia. It was found that combinations of tests lead to increased levels of diagnostic sensitivity compared with single tests. When taken in combination with other investigations, our results suggest that assessment for psychiatric disorders, delayed memory decline, adaptive behavior decline, and the presence of seizures would be useful for the diagnosis of dementia and that dementia scales would provide additional useful information. The authors conclude that combinations of tests and scales will be most useful for diagnosing dementia in adults with intellectual disabilities. The authors suggest that further research is needed to promote rapid progress, with studies that focus on common diagnostic methodology, identification of screening instruments, and amounts of decline indicative of dementia.