Impact of cardiometabolic factors and AD plasma biomarkers on white matter hyperintensities volume in individuals with cognitive complaints from the global south
Impact of cardiometabolic factors and AD plasma biomarkers on white matter hyperintensities volume in individuals with cognitive complaints from the global south
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, Aβ42/Aβ40 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, Aβ42/40, 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 and 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, and cerebrospinal fluid circulation in underrepresented geographical contexts.
Cardiometabolic factors, Dementia-free cognitive complaint individuals, Neurodegeneration blood biomarkers, White matter hyperintensities
270-279
Riquelme-Contreras, Patricio
76927e0a-6a2d-49d3-8bf4-5cb4f56285c2
Henriquez, Fernando
19ef66aa-6f10-41fe-a210-0353c8b4f72f
Gonzalez-Campo, Cecilia
fbf8f925-e61b-4ca5-87ee-10ef4da85873
Hornberger, Michael
a48c1c63-422a-4c11-9a51-c7be0aa3026d
17 January 2026
Riquelme-Contreras, Patricio
76927e0a-6a2d-49d3-8bf4-5cb4f56285c2
Henriquez, Fernando
19ef66aa-6f10-41fe-a210-0353c8b4f72f
Gonzalez-Campo, Cecilia
fbf8f925-e61b-4ca5-87ee-10ef4da85873
Hornberger, Michael
a48c1c63-422a-4c11-9a51-c7be0aa3026d
Riquelme-Contreras, Patricio, Henriquez, Fernando and Gonzalez-Campo, Cecilia
,
et al.
(2026)
Impact of cardiometabolic factors and AD plasma biomarkers on white matter hyperintensities volume in individuals with cognitive complaints from the global south.
Neuroscience, 595, .
(doi:10.1016/j.neuroscience.2025.11.013).
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, Aβ42/Aβ40 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, Aβ42/40, 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 and 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, and cerebrospinal fluid circulation in underrepresented geographical contexts.
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Accepted/In Press date: 8 November 2025
e-pub ahead of print date: 10 December 2025
Published date: 17 January 2026
Keywords:
Cardiometabolic factors, Dementia-free cognitive complaint individuals, Neurodegeneration blood biomarkers, White matter hyperintensities
Identifiers
Local EPrints ID: 510038
URI: http://eprints.soton.ac.uk/id/eprint/510038
ISSN: 0306-4522
PURE UUID: 983625c2-9552-4508-a7d6-71d081672482
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Date deposited: 16 Mar 2026 17:38
Last modified: 19 Mar 2026 03:16
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Contributors
Author:
Patricio Riquelme-Contreras
Author:
Fernando Henriquez
Author:
Cecilia Gonzalez-Campo
Author:
Michael Hornberger
Corporate Author: et al.
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