A NEW study has found that Alzheimer’s disease in adults with Down syndrome develops rapidly after the onset of amyloid-β positivity, with cognitive decline and tau deposition occurring within a few years. This new timeline, established using amyloid age and tau-PET, offers critical insights for clinical practice and Alzheimer’s disease trials.
Adults with Down syndrome are at higher risk for developing Alzheimer’s disease, yet the timeline of disease progression remains poorly understood. Natural history studies have explored biomarkers such as amyloid-β and tau, but this study aims to refine that understanding by identifying the onset of symptomatic Alzheimer’s based on these biomarkers. Specifically, it uses a concept called “amyloid age,” derived from amyloid-PET scans, to track the progression of Alzheimer’s disease and its relationship to tau burden, offering a more precise framework for predicting disease onset.
In this longitudinal cohort study, data were collected from 167 adults with Down syndrome at four research sites across the UK and USA, as part of the Alzheimer’s Biomarker Consortium-Down Syndrome (ABC-DS) study. The participants, aged 25 and older, were assessed for cognitive performance and underwent amyloid-PET and tau-PET scans over a median follow-up of 32 months. Generalised linear regression models revealed significant associations between amyloid age and both cognitive performance and tau deposition, with cognitive decline and tau increases observed as early as 2.7 years after the detection of amyloid β positivity. Furthermore, the study found that mild cognitive impairment typically occurred at an amyloid age of 7.4 years, while dementia was observed at 12.7 years. These findings suggest that the disease progresses swiftly once amyloid β positivity and tau deposition are detected.
This study underscores the importance of monitoring amyloid and tau levels in clinical practice for adults with Down syndrome, as early identification of Alzheimer’s disease onset can lead to timely interventions. Additionally, the use of amyloid age as a predictor of cognitive decline has important implications for Alzheimer’s disease clinical trials, providing a more accurate and biomarker-based approach to studying disease progression in this population. Future studies should focus on validating these findings across broader cohorts and refining strategies for early intervention.
Reference
Schworer E K et al Timeline to symptomatic Alzheimer’s disease in people with Down syndrome as assessed by amyloid-PET and tau-PET: a longitudinal cohort study. The Lancet Neurology. 2024;23(12):1214-1224.
