Biomarkers

Area of Science:

• Neurology
• Neuroimaging
• Alzheimer's Disease Research

Background:

• White matter hyperintensities (WMH) are common in elderly individuals and Alzheimer's disease (AD) patients.
• The underlying pathophysiology of WMH in AD remains unclear.
• This study investigates the causes and cognitive associations of WMH in biologically diagnosed AD patients.

Purpose of the Study:

• To explore the etiologies of global and regional white matter hyperintensities (WMH) in Alzheimer's disease (AD) patients.
• To examine the cognitive correlates of WMH burden in a cohort of AD patients.
• To investigate the relationship between WMH, AD biomarkers, and cognitive decline.

Main Methods:

• A cross-sectional study of 170 AD patients with cerebrospinal fluid (CSF) biomarkers, MRI scans, and cognitive assessments (CDR, MMSE).
• Semiquantitative scales were used to assess WMH and atrophy.
• Linear regression models analyzed associations between WMH, age, cerebral microbleeds (CMB), AD biomarkers, atrophy, and vascular risk factors, adjusting for covariates.

Main Results:

• Global WMH in AD patients were associated with older age, lower CSF Aβ42 levels, and more severe cerebral microbleeds (CMB).
• Regional WMH (paraventricular, frontal, parietal) showed associations with age, CMB, and CSF Aβ42 levels.
• Lower Mini-Mental State Examination (MMSE) scores were significantly linked to increased paraventricular WMH and medial temporal atrophy (MTA) after adjusting for age, sex, and education.

Conclusions:

• In AD patients, WMH, particularly in frontal, parietal, and paraventricular regions, are associated with AD pathology (CSF Aβ42, CMB), not vascular risk factors or tau.
• Paraventricular WMH are significantly associated with cognitive decline in AD patients.
• The link between paraventricular WMH and cognitive decline is independent of cortical atrophy.