Summary:
Researchers at Johns Hopkins used artificial intelligence to analyze chest CT and brain MRI scans and found that lower thoracic vertebral bone mineral density is associated with faster cognitive decline and greater microstructural white matter damage. The results suggest shared systemic metabolic processes that simultaneously weaken bone and accelerate brain aging.
Key Facts:
- Accelerated Cognitive Decline: Lower baseline thoracic volumetric bone mineral density (vBMD) from chest CT scans was linked to a more rapid decline in overall cognitive performance over time.
- Targeted White Matter Vulnerability: Reduced spinal bone density correlated with microstructural deterioration in networks tied to executive function, including greater white matter hyperintensities in the corpus callosum and faster fractional anisotropy loss in the anterior limb of the internal capsule.
- Shared Metabolic Drivers Rather Than Direct Causation: The authors emphasize that bone loss does not directly cause dementia; instead, both bone and brain deterioration appear to stem from overlapping metabolic aging mechanisms such as insulin resistance, lipid abnormalities, and hormonal changes associated with menopause.
Source: Radiological Society of North America (RSNA) and Johns Hopkins Medicine
Uncovering the Link Between Bone Health and Brain Aging
Bone mineral density is a standard marker of skeletal strength; when it declines, bones become more fragile and susceptible to fractures. Though osteoporosis and cognitive impairment commonly occur together in older adults, research has typically examined the skeleton and the brain separately.
A new study published in Radiology by investigators at Johns Hopkins University presents longitudinal evidence that spinal bone loss is closely associated with accelerated brain degeneration and cognitive decline.
Applying a deep learning model to routine clinical imaging, researchers found that people with lower thoracic vertebral vBMD experienced quicker cognitive decline and progressive microstructural injury in key white matter tracts.
“This is the first longitudinal secondary analysis linking baseline vertebral bone mineral density to subsequent changes in white matter structure, white matter hyperintensity progression, and cognition,” said senior author Shadpour Demehri, M.D., professor of radiology at Johns Hopkins University. “By combining imaging and clinical assessments, our study indicates that baseline bone density is associated with both functional and structural measures of age-related brain degeneration.”
AI Extracts Opportunistic Biomarkers from Routine Scans
The team, led by postdoctoral fellow Sara Momtazmanesh, M.D., analyzed data from the Multi-Ethnic Study of Atherosclerosis (MESA). They used a deep learning algorithm developed in Dr. Demehri’s lab to quantify thoracic vertebral vBMD from noncontrast chest CT scans in 2,086 individuals.
From that pool, a final cohort of 715 participants had both validated vBMD measurements and completed multimodal brain MRI exams along with longitudinal cognitive testing.
To measure brain changes, the investigators tracked two imaging markers of vascular and microstructural injury:
- White Matter Hyperintensities (WMHs): Bright regions on MRI that reflect small vessel disease and focal ischemic damage. Longitudinal WMH data were available for 408 participants.
- Fractional Anisotropy (FA) Decline: A diffusion MRI metric that indicates loss of white matter tract integrity. Longitudinal FA measurements were analyzed for 405 participants.
Analyses showed participants with lower baseline spinal bone density had a faster decline in global cognition. Structural damage appeared concentrated in functionally important hubs: individuals with lower vBMD displayed greater WMH accumulation in the corpus callosum—critical for working memory and executive processes—and steeper FA decline in the anterior limb of the internal capsule.
A Shared Metabolic Decline
The investigators caution against interpreting the results as evidence that osteoporosis causes dementia. Instead, the patterns point to a shared metabolic decline that can damage both bone and brain over time.
“Our findings reflect an overlapping metabolic syndrome that may underlie degeneration of both organ systems,” Dr. Demehri explained. “Factors such as insulin resistance, dyslipidemia, and menopausal hormonal changes likely contribute to parallel aging processes rather than a direct bone-to-brain causal pathway.”
Opportunistic Screening for At-Risk Individuals
Millions of people undergo chest CT scans each year for lung cancer screening, coronary calcium scoring, or pulmonary follow-up. AI tools can opportunistically measure spinal bone density from these existing scans without extra radiation or cost. Identifying early bone loss on routine imaging could flag patients at higher risk for accelerated cognitive decline and prompt combined preventive strategies.
“Diagnostic images contain vast amounts of information that AI can now synthesize across organ systems,” Dr. Demehri said. “This enables new opportunities to link coexisting age-related conditions that were previously studied separately and to investigate shared biological pathways and potential common mechanisms.”
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by staff.
- Additional context was added by the editorial team.
About this Genetics and Neuroregeneration Research:
- Media Contact: Linda Brooks
- Source: RSNA
- Image Credit: Image credited to Neuroscience News
- Original Research (Open Access): Radiology (September 22, 2026). “Deep Learning-derived Bone Mineral Density and Longitudinal White Matter Microstructure and Cognitive Decline: Multi-Ethnic Study of Atherosclerosis.” Authors: Sara Momtazmanesh et al.
- DOI: 10.1148/radiol.260656
Abstract
Deep Learning-derived Bone Mineral Density and Longitudinal White Matter Microstructure and Cognitive Decline: Multi-Ethnic Study of Atherosclerosis
Background
White matter microstructural degeneration and white matter hyperintensities are established imaging markers of brain aging. Low bone mineral density and brain aging often occur together, but longitudinal evidence that links skeletal health with progressive white matter injury and cognitive decline has been limited.
Purpose
The study aimed to determine whether deep learning–derived thoracic vertebral BMD (vBMD) from noncontrast chest CT scans is associated with longitudinal changes in white matter integrity, white matter hyperintensity burden, and cognitive decline.
Materials and Methods
This secondary analysis used data collected from September 2016 to March 2024 from the Multi-Ethnic Study of Atherosclerosis. Participants without clinically recognized cardiovascular disease underwent noncontrast chest CT, multimodal brain MRI (including diffusion tensor imaging and fluid-attenuated inversion recovery), and serial cognitive testing. Baseline thoracic vBMD was quantified with a validated deep learning algorithm. Linear mixed-effects models tested associations between baseline vBMD and longitudinal changes in WMH volume, white matter fractional anisotropy, and cognition, adjusting for demographics, APOE-ε4 status, cardiometabolic risk factors, lifestyle, and medications.
Results
The analysis included 715 participants (median age 69 years; interquartile range 65–75; 397 men, 318 women). Lower baseline vBMD was linked to a faster decline in total white matter fractional anisotropy (n = 405; β = −0.036 SD/year per 0.1 g/cm³ vBMD decrease; nominal P = .02), though this finding did not meet false discovery rate correction (adjusted P = .07). Regionally, lower vBMD was associated with a faster FA decline in the anterior limb of the internal capsule (β = −0.048 SD/year; adjusted P = .006) and greater WMH accumulation in the corpus callosum (n = 408; β = 12.8%/year; adjusted P = .04). Lower vBMD was also associated with faster decline in a global cognitive composite (n = 639; β = −0.025 SD/year; P = .002) and on the Cognitive Abilities Screening Instrument (n = 675; β = −0.320/year; P < .001). Diabetes strengthened the association with WMH progression (β = 4.99%; P = .03).
Conclusion
Lower thoracic vBMD derived from routine noncontrast chest CT was associated with modestly accelerated regional white matter injury and faster cognitive decline, particularly among participants with diabetes. These results support the potential utility of opportunistic vBMD assessment to detect accelerated brain aging.
ClinicalTrials.gov: NCT00005487