Abstract

White matter hyperintensities (WMH) are a magnetic resonance imaging (MRI) sign associated with cognitive complaints in the Alzheimer's Disease (AD) continuum, including the pre-dementia steps. Cardiovascular and neurodegenerative pathophysiology have been postulated as relevant factors in the origin of WMH in AD. However, this evidence comes mainly from northern global populations, where the epidemiological profile differs from other geographical regions. This study explores the relationship between WMH, cardiometabolic and plasma neurodegeneration biomarkers in individuals with cognitive complaints from a developing country in the global south, where cardiometabolic risk factors are highly prevalent. We analyzed 112 individuals with cognitive complaints, assessing plasma pTau217, A(342/A(340 ratio, blood pressure, and glycemia levels while quantifying and segmenting WMH volumes. Multiple regression analyses revealed that diastolic blood pressure was significantly associated with WMH in specific white matter tracts, including the anterior thalamic radiation, cingulum, forceps minor, and subcortical regions. In contrast, no associations were found with glycemia, pTau217, A(342/40, or systolic blood pressure. These findings suggest that cardiovascular factors could be more critical in WMH development than neurodegeneration markers in this population. Our study, in addition to reflecting, in part, the associations between cardiovascular risk factors , WMH, highlights the need for further research on neurovascular contributions to dementia pathophysiology in these populations, emphasizing the role of neurovascular integrity, blood-brain barrier function , cerebrospinal fluid circulation in underrepresented geographical contexts.