Lower Spinal Bone Density Linked to Faster Cognitive Decline

Lower bone density in the spine is associated with faster cognitive decline and changes in brain white matter, especially in people with diabetes, a new longitudinal analysis showed.Using a deep learning model to assess clinical imaging data of over 700 older adults, researchers found that lower vertebral bone mineral density (vBMD) in the thoracic vertebrae was associated with faster decline in global cognition over approximately 5 years.Lower vBMD was also associated with faster accumulation of white matter hyperintensities (WMHs) in the corpus callosum, which is involved in executive functioning, working memory, and attention. Individuals with lower vBMD also showed greater loss of white matter integrity — measured by fractional anisotropy (FA) — in the anterior limb of the internal capsule, which also plays a role in executive function.“This comprehensive study using both imaging and clinical assessments sends a clear signal that bone density at baseline is associated with both functional and imaging measures of age-related brain degeneration,” investigator Shadpour Demehri, MD, professor of radiology at Johns Hopkins University in Baltimore, said in a statement.The study was published online on September 22 in Radiology.Connecting Bone and BrainBMD is commonly used to assess skeletal health, and lower density is associated with a higher risk for osteoporosis and fractures. Previous research has also suggested a link between bone health and cognitive function, potentially through shared metabolic and vascular risk factors.However, less is known about the link between lower bone density and changes in brain structure and cognition over time.Investigators conducted a secondary longitudinal analysis of participants in the Multi-Ethnic Study of Atherosclerosis. Using a deep learning algorithm, they measured thoracic vBMD from noncontrast chest CT scans in 2086 participants. The final cohort included 715 participants (median age, 69 years; 55.5% men) who had vBMD measurements as well as brain MRI scans and longitudinal cognitive testing.Participants with prior dementia or stroke at baseline were excluded.The primary cognitive outcome was a global cognitive composite, with additional tests assessing global cognition, processing speed, attention, and working memory.Participants were followed for approximately 5 years. Longitudinal WMH data were available for 408 participants, while FA data were available for 405. Analyses accounted for demographic characteristics and multiple cardiovascular, metabolic, lifestyle, and medication-related factors.Lower spinal bone density was associated with a faster and greater decline in global cognition over time, even after controlling for physical activity, cardiovascular risk factors, age, sex, and race or ethnicity. Each 0.1-g/cm3 decrease was linked to an additional 0.025-SD decline in the global cognitive composite per year (P = .002), or about 0.15 SD over 5 years.Although there was no significant link between lower bone density and total WMH accumulation in the corpus callosum, each 0.1-g/cm3 decrease in vBMD was associated with 12.8% faster annual accumulation of WMH (false discovery rate [FDR]-adjusted P = .04).White matter integrity, as measured by FA, also declined more rapidly in the anterior limb of the internal capsule, with a 0.048-SD greater annual decline for each 0.1-g/cm3 decrease in vBMD (FDR-adjusted P = .006). However, there was no association between vBMD and total white matter FA.Lower bone density was also associated with faster decline on the Cognitive Abilities Screening Instrument, another measure of global cognition. For each 0.1-g/cm3 decrease in vBMD, cognitive scores declined by an additional 0.32 points per year (P < .001). There was no link to significant changes in processing speed, attention, or working memory scores.The association between lower vBMD and faster WMH accumulation was seen only among participants with diabetes. In a post hoc analysis, each 0.1-g/cm3 decrease in vBMD was associated with a 4.99% faster annual rate of WMH accumulation in this group (P = .03). The investigators cautioned that this subgroup finding needs to be replicated.What Bone Density May ShowLower bone density was associated with several markers of brain aging, but the findings do not show that low vBMD itself causes cognitive decline or dementia, the investigators acknowledged. Instead, vBMD may reflect underlying processes that affect both bone and brain health.Spinal bone density may be “an integrative marker of cumulative systemic health, reflecting factors such as lifelong inflammation, metabolic dysfunction, physical inactivity, and frailty, rather than directly driving brain aging,” they wrote.In addition, the use of AI to extract vBMD from chest CT scans allowed the investigators to examine skeletal health alongside changes in the brain. “Diagnostic images contain an immense amount of data that AI can now synthesize at scale across multiple organ systems,” Demehri said.For now, however, the findings remain observational. The study cannot establish causality, and residual confounding is possible. The associations were relatively modest and were not consistent across all brain and cognitive measures, limiting the utility of vBMD as a predictor of cognitive decline for individual patients.Before CT-derived vBMD could be used routinely, it would need to be validated across different scanners and imaging protocols and in clinical settings, researchers noted.Disclosure information for study authors is available in the original study publication.