A preprint analyzing 30,000 MRIs from the UK Biobank identifies choroid plexus calcification as a new radiation-free marker of brain aging, distinct from plexus volume and most strongly linked to diabetes, obesity, and hypertension in the understudied third ventricle
A preprint analyzing 30,000 MRIs from the UK Biobank identifies choroid plexus calcification as a new radiation-free marker of brain aging, distinct from plexus volume and most strongly linked to diabetes, obesity, and hypertension in the understudied third ventricle
In a preprint dated September 16, researchers at the University of Southern California measured choroid plexus calcification at an unprecedented scale in 30,012 UK Biobank participants, a cohort drawn from half a million residents of the United Kingdom. Calcification increased with age, was higher in men, and its associations with diabetes, obesity, smoking, and hypertension were strongest in the third ventricle.
The choroid plexus is a network of vascularized tissue lining the brain's cavities (the ventricles), forming the barrier between blood and cerebrospinal fluid. Its calcification with age is a routine finding: CT data show it in 60 to 70% of middle-aged and older adults. Yet measuring it in large samples has been nearly impossible. CT involves ionizing radiation, and conventional MRI cannot distinguish calcified tissue from the rest, so neuroimaging of the choroid plexus has generally been limited to its volume, a much cruder indicator.
The authors used QSM, a technique that reveals calcium deposits on MRI without radiation, and measured calcification separately in the lateral, third, and fourth ventricles. Calcification increased with age most steeply in the lateral ventricles and was higher in men. Plexus volume, by contrast, grows faster in women according to prior data and correlated with calcification only weakly. "These are not interchangeable measures; they appear to reflect different aspects of choroid plexus pathology," the authors write.
The strongest and most consistent associations were between calcification and diabetes, obesity, smoking, hypertension, and ischemic heart disease, specifically in the third ventricle, even after adjusting for plexus volume. Among participants who received their diagnosis after the scan, calcification was already elevated before the diagnosis was made. A similar signal had appeared earlier: in a prior study, calcification (not volume) predicted microglial activation, the brain's immune response, in the cortex.
The choroid plexus of the third ventricle lies adjacent to the hypothalamus, and its capillaries pass signals from the bloodstream into the brain directly. The authors suggest this is why disruptions such as diabetes and hypertension manifest as calcification most rapidly at this site. "This region remains relatively understudied in the choroid plexus imaging literature," they note.
Two months ago, a separate group working in the same cohort reported that greater plexus volume predicts a 1.6-fold higher risk of dementia, while high signal intensity predicts a more than twofold lower risk, with Mendelian randomization (a genetic test of causality) supporting a causal contribution. That finding prompted the current work: if volume matters for dementia risk but captures plexus tissue only crudely, what would calcification reveal? One additional, still preliminary signal: calcification was also higher in individuals with a maternal history of Alzheimer's disease.
The study was led by Neda Jahanshad, a member of ENIGMA, the world's largest neuroimaging genetics consortium (1,400+ scientists, 43 countries).
QSM offers a radiation-free way to detect this marker of brain aging, one that is distinct from plexus volume, tracks with metabolic and vascular risk factors, and by the first preliminary signal, with dementia risk as well. It can be incorporated into existing MRI protocols without additional equipment and monitored across large populations.