Potential of facial biomarkers for Alzheimer's disease and obstructive sleep apnea in Down syndrome and general population

Down syndrome (DS), caused by trisomy 21, is associated with an increased risk of Alzheimer's disease (AD) and obstructive sleep apnea (OSA). Traditional diagnostic methods for AD and OSA, like cerebrospinal fluid analysis and polysomnography, are invasive and challenging for people with DS. In this study, we assessed whether facial morphology could be used as a potential noninvasive biomarker for these conditions in both DS and the general population. We performed a comprehensive 3D analysis of facial shape variation by registering the 3D coordinates of 21 landmarks on facial models extracted from magnetic resonance images of 131 individuals with DS and 216 euploid (EU) adult controls, including AD and OSA cases. Procrustes ANOVA and MANOVA quantified shape variation by sex, age, and facial size, while geometric morphometrics assessed diagnostic group differences. Significant facial shape differences were observed between the DS and EU groups, indicating sex-dependent differences and altered age-related changes in DS, particularly in females. Facial shape correlated with the amyloid beta ratio (Aβ1-42/Aβ1-40), a key AD biomarker. In DS, facial shape differences by AD diagnosis were not significant after adjusting for age and facial size, but significant shape differences were detected in the EU population. For OSA, facial shape correlated with the apnea–hypopnea index (AHI), and DS individuals with severe OSA showed distinct facial morphology compared with those without OSA, suggesting an association between facial shape and sleep respiratory disturbances. These results highlight the potential of facial morphology as a noninvasive biomarker for AD and OSA detection and management.