Although life-spans of individuals with Down syndrome have increased dramatically in recent years—now reaching into the late 50s and early 60s—these adults continue to experience health declines in their later years. With the exception of Alzheimer's dementia, however, few studies have examined Down syndrome health issues across the decades of adulthood. In this study, we utilize five separate databases—collected for different purposes and at different times—to examine cross-sectional changes in the levels of overall health and percentages experiencing specific aging-related health conditions. Especially by their 50s, adults with Down syndrome show general health declines, with 1/3 or more rated as having “poor” or “fair” overall health. From Tennessee's National Core Indicators (NCIs) and the national DS-Connect databases, percentages of Alzheimer's dementia rise in the 50s and again in the 60s; increasing percentages are also found of diabetes, skeletal problems, and cardiovascular problems. After documenting age-related health changes, we evaluate the use of large-scale databases to inform us about aging-related health changes, especially given potential limitations of using diverse and non-medical respondents as well as triangulation as a research method. Beyond needing more, more diverse, and higher-quality health studies in the future, we need to consider the ways in which Down syndrome constitutes a health condition; how aging-related health changes may interact with family coping and individual family members; and how such changes impact residential settings, work activities, daily living skills, and community involvement.