More White Matter Hyperintensities, Greater Cognitive Decline

Researchers here show that the burden of white matter hyperintensities in the brain correlates with both age and with loss of cognitive function. A white matter hyperintensity is named for its appearance in MRI images of the brain, and is an area of damaged tissue. The cause can include rupture of small blood vessels, which is increasingly common with advancing age, particularly in patients with hypertension, or forms of inflammation and scarring, often associated with leakage of the blood-brain barrier, another issue that becomes prevalent with age. These incidences of damage to the brain are individually minor, but collectively add up over time.

To elucidate the relationship between aging and cognitive decline, it is important to understand the structural changes in the brain that occur throughout aging as a potential mechanistic explanation. One example of structural changes that are typically associated with older age is the presence of white matter hyperintensities (WMHs). WMHs are a neuroimaging marker of small vessel disease and are often indicative of chronic, insufficient cerebrovascular supply.

The accrual of WMHs is a subtle, progressive process typically associated with cardiovascular risk factors (e.g., body mass index, hypertension, or diabetes) and aging. There is also evidence that both age and cardiovascular risk factors predict increasing WMH load over time. This is supported by findings suggesting that increasing physical activity or controlling vascular risk factors such as blood pressure can slow the progression of WMHs.

We aimed to investigate if WMH load is a mediator of the relationship between age and cognitive decline. Healthy participants (N = 166, 20-80 years) completed the Montreal Cognitive Assessment (MoCA). WMHs were manually delineated on fluid-attenuated inversion recovery (FLAIR) scans. Mediation analysis was conducted to determine if WMH load mediates the relationship between age and cognition. Older age was associated with worse cognition, but this was an indirect effect: older participants had more WMHs, and, in turn, increased WMH load was associated with worse MoCA scores. Thus WMH load mediates the relationship between age and cognitive decline. Importantly, this relationship was not moderated by age, i.e., increased WMH severity is associated with poorer MoCA scores irrespective of age.