The meaning of white spots

The bright white spots detected on a brain MRI are lesions called white matter hyperintensities (WMHs). They appear to indicate the presence of a problem in the white matter of the brain and the possibility of structural abnormalities.

These lesions are quite common in people aged over 60 and their frequency gradually increases with age. Around 20% of people over 60 and over 90% of people over 80 are affected.

Studies have highlighted that these small lesions of the white matter could be linked to the thinning of the cerebral cortex.

Today, a new study published in the journal Nature Communications demonstrates that this is the case.

In collaboration with colleagues in the United States and Europe from the CHARGE (Cohorts of Heart and Aging Research in Genomic Epidemiology) consortium, researchers from the University of Montreal have identified clear genetic reasons explaining why HSB appears so commonly in older people.

“We set out to study HSB and their potential link with cortical atrophy, a dominant characteristic of dementia,” mentions Zdenka Pausova, professor of pediatrics at UdeM and researcher at CHU Sainte-Justine. We were motivated by a crucial question: could genetic factors underlie the association between HSB and cortical thinning and could they also explain part of the observed dementia risk? Our findings confirmed that it is possible.”

More than 50,000 participants

In their large-scale investigation into the genetics of HSB-associated cortical thinning, Zdenka Pausova and colleagues collected and analyzed data from 51,065 participants across 10 cohorts. All were of European ancestry, with the youngest subject being 19 years old and the oldest being 100 years old.

“The results established that, across all cohorts, higher HSB volume was consistently associated with reduced cortex thickness,” said study co-senior author Tomas Paus, professor of psychiatry and neuroscience at the UdeM and researcher at CHU Sainte-Justine.

“This was true even after taking into account typical vascular risk factors like hypertension and diabetes,” added Zdenka Pausova. The strongest correlation was observed in the insula, a key brain region for the integration of sensory, emotional and cognitive functions.

A genome-wide association study (meta-GWAS) was performed to explore the genetic loci associated with this HSB-related cortical atrophy. The researchers uncovered 20 significant loci, 15 of which influence genes in the cortex, particularly those active in axonal transport and cytoskeletal organization which are essential for maintaining neuronal health.

Additionally, these genetic signals were enriched in vascular cell types and cells supporting neuronal health, such as astrocytes and oligodendrocytes. According to the scientists, this pattern reflects the hypothesis that disruptions in small blood vessels and axonal health may contribute to cortical thinning, thereby linking vascular risk to cortical atrophy.

“A particularly important aspect of our study was the construction of a polygenic risk score based on our meta-GWAS,” said Zdenka Pausova. When applied to an independent dataset of 500,000 individuals in Finland, it demonstrated that greater genetic vulnerability to HSB-related cortical atrophy correlates with increased risk of vascular dementia and dementia all confused causes.”

The scientists who conducted this study conclude that this finding highlights the need to consider the vascular health and genetic susceptibility of certain individuals when understanding dementia risk.