Brain lesions in Down syndrome show unexpected reversible changes

What has long been interpreted as permanent and irreversible vascular damage may not be exclusively so. In people with Down syndrome-one of the most robust populations for studying Alzheimer's disease due to the near-universal presence of the characteristic proteinopathies of this dementia from the age of 40-some lesions visible on magnetic resonance imaging do not follow a linear course. A longitudinal study from the Institut de Recerca Sant Pau (IR Sant Pau), published in Alzheimer's & Dementia, shows that these alterations can fluctuate and even decrease over time in the Down syndrome population. This is especially true once the clinical symptoms of Alzheimer's disease have begun to manifest.

The study analyzed the evolution of white matter hyperintensities (WMH), lesions typically associated with cerebral vascular alterations that appear as brighter areas on magnetic resonance imaging. These alterations are considered a marker of small vessel disease and have been linked to cognitive impairment in different contexts.

Previous studies from IR Sant Pau had shown that, in people with Down syndrome, the burden of these lesions increases with age and is associated with characteristic Alzheimer's biomarkers, such as beta-amyloid and phosphorylated tau proteins. However, those studies were cross-sectional and provided a snapshot of the disease at different time points, without allowing observation of its evolution within the same individuals.

"The cross-sectional analysis gives us a snapshot of each stage of the process, but it does not show how these alterations change within each individual over time. With this study, we were able to see the movie and confirm that the trajectory is not always linear," explains Alejandra Morcillo-Nieto, researcher in the Brain Imaging and Aging group at IR Sant Pau and first author of the article.