Deep Learning-derived Bone Mineral Density and Longitudinal White Matter Microstructure and Cognitive Decline: Multi-Ethnic Study of Atherosclerosis.

Abstract

Background White matter (WM) microstructural degeneration and WM hyperintensities (WMH) are imaging markers of brain aging. Low bone mineral density (BMD) and brain aging co-occur, but longitudinal evidence linking skeletal health to WM injury and cognitive decline remains limited. Purpose To determine whether deep learning-derived thoracic vertebral BMD (vBMD) from noncontrast chest CT is associated with longitudinal changes in WM integrity, WMH burden, and cognitive decline. Materials and Methods This secondary analysis of a prospective study conducted from September 2016 to March 2024 included participants without clinically recognized cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis. Participants underwent noncontrast chest CT, multimodal brain MRI (diffusion tensor imaging and fluid-attenuated inversion recovery), and cognitive testing. Thoracic vBMD was quantified at baseline using a validated deep learning algorithm. Linear mixed-effects models related baseline vBMD to longitudinal changes in WMH volume, WM fractional anisotropy, and cognition, adjusting for demographics, apolipoprotein E-ε4, cardiometabolic risk factors, lifestyle, and medications. Results This study included 715 participants (median age [IQR], 69 years [65-75 years]; 397 men and 318 women). Lower baseline vBMD was associated with faster decline in total WM fractional anisotropy (n = 405; β = -0.036 SD/year/0.1 g/cm³ vBMD decrease [95% CI: -0.065, -0.006]; nominal P = .02), although this did not survive false discovery rate correction (adjusted P = .07). Regionally, lower vBMD was associated with faster fractional anisotropy decline in the anterior limb of the internal capsule (β = -0.048 SD/year; adjusted P = .006) and faster WMH accumulation in the corpus callosum (n = 408; β = 12.8%/year; adjusted P = .04). Lower vBMD was also associated with faster decline in the global cognitive composite (n = 639; β = -0.025 SD/year; P = .002) and the Cognitive Abilities Screening Instrument (n = 675; β = -0.320/year; P < .001). Diabetes amplified associations with WMH progression (β = 4.99%; P = .03). Conclusion Lower vBMD from noncontrast chest CT was associated with modestly accelerated regional WM injury and faster cognitive decline, particularly among participants with diabetes, suggesting utility for detecting accelerated brain aging. ClinicalTrials.gov: NCT00005487 © RSNA, 2026 Supplemental material is available for this article.