Lower Bone Density Linked to Cognitive Decline

Chest CT-derived bone density was associated with changes in cognition and brain white matter


Sara Momtazmanesh, MD
Momtazmanesh
Shadpour Demehri, MD
Demehri

Researchers at Johns Hopkins University found that lower bone mineral density in the spine was associated with faster cognitive decline and accelerated age-related white matter injury, according to a new study published today in Radiology.

Low bone mineral density is associated with skeletal fragility, but its relationship with brain function is not well understood.

A multidisciplinary research team led by Sara Momtazmanesh, MD, postdoctoral research fellow in the Department of Radiology and Radiological Sciences at Johns Hopkins University in Baltimore, Maryland, conducted a secondary analysis of data from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants underwent non-contrast chest CT, multimodal brain MRI and cognitive testing.

The researchers used a deep learning algorithm developed in the Johns Hopkins University lab of Shadpour Demehri, MD, professor of radiology, to calculate baseline thoracic vertebral volumetric bone mineral density (vBMD) derived from the non-contrast chest CT scans of 2,086 MESA participants. The final study cohort included 715 participants with an established vBMD who underwent both MRI and cognitive testing.

MRI exams were analyzed for white matter hyperintensities and reduced fractional anisotropy, microstructural brain changes that are associated with cognitive decline and increased dementia risk. Longitudinal data for white matter hyperintensities and fractional anisotropy were available for 408 and 405 participants, respectively.

Three forest plots assess modifiers of associations between vertebral bone mineral density and changes in white matter hyperintensities, fractional anisotropy and global cognition. Diabetes significantly modifies white matter hyperintensity accumulation; sex and triglycerides show suggestive modification of fractional anisotropy and global cognition, respectively.

Effect modification of vertebral bone mineral density associations with longitudinal brain aging outcomes. (A) White matter hyperintensity (WMH) accumulation (n = 408) is shown, with percentage change per year in log-transformed WMH volume plotted on the x-axis. Diabetes status shows effect modification. (B) Fractional anisotropy (FA) change (n = 405) is shown. Sex shows suggestive effect modification. (C) Global cognitive composite (GCC) change (n = 639) is shown, with SD per year in z-standardized GCC plotted on the x-axis. APOE = apolipoprotein E.

https://doi.org/10.1148/radiol.260656 ©RSNA 2026

Lower Bone Density, Faster Cognitive Decline

The results showed that lower baseline vBMD was associated with faster decline in global cognition.

The researchers observed associations in specific brain regions: lower vBMD was associated with white matter hyperintensities accumulation in the corpus callosum, which supports executive functioning, working memory and attention. Lower vBMD was also associated with a steeper decline in total white matter fractional anisotropy in the anterior limb of the internal capsule, which is also involved in executive function.

“This study is the first longitudinal secondary analysis linking baseline vertebral bone mineral density to changes in white matter structure, white matter hyperintensity progression and cognition,” Dr. Demehri said. “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.”

The researchers cautioned that the findings do not suggest that osteoporosis causes dementia.

“This study is not about cause and effect, but rather the observation of a metabolic syndrome that may cause both bone and brain degeneration,” Dr. Demehri said. “The co-occurrence observed in the study may reflect shared metabolic drivers of aging, including insulin resistance, dyslipidemia, and menopausal change, rather than a direct bone-to-brain effect.”

The researchers said identifying individuals with low vBMD may help flag those at risk for parallel skeletal and neurologic decline, allowing earlier screening and shared risk-factor management.

“Chest CT is done for lung cancer screening, calcium scoring, nodule follow-up, and many other indications, Dr. Momtazmanesh said. “These scans could provide an opportunistic measurement of bone density from the thoracic spine that is associated with a loss of cognitive function.”

Dr. Demehri concurred: “Diagnostic images contain an immense amount of data that AI can now synthesize at scale across multiple organ systems. This creates a robust, newly feasible opportunity to interconnect co-existing age-related pathologies that have traditionally been studied in isolation and to identify shared biological pathways and potential common causal mechanisms.”

For More Information

Access the Radiology article, “Deep Learning-derived Bone Mineral Density and Longitudinal White Matter Microstructure and Cognitive Decline: Multi-Ethnic Study of Atherosclerosis.”

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