Atorvastatin Mitigates WMH-Related Cognitive Impairment by Reducing VCAM-1

Atorvastatin Mitigates WMH-Related Cognitive Impairment by Reducing VCAM-1: A Randomized, Double-Blind, Placebo-Controlled Study

This prospective study will enroll patients younger than 60 years with ischemic white matter lesions (WMIL) and age-matched healthy controls. We will measure circulating endothelial-related biomarkers, including endothelial progenitor cells (EPCs), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), asymmetric dimethylarginine (ADMA), and homocysteine (Hcy). We will also assess transcription levels of ICAM-1, VCAM-1, and ADMA. All participants will be followed and managed for 2 years, with repeated assessments of endothelial biomarkers and their transcriptional levels, as well as clinical and imaging evaluations. The aims are to characterize changes in endothelial biomarkers in WMIL, to determine how these changes relate to clinical features and imaging progression, and to evaluate whether statins protect endothelial function-by modifying these biomarkers-and thereby help treat WMIL and slow its progression.

Inclusion Criteria:

• Age 45-60 years.
• Provides written informed consent.
• WMIL group: consecutive outpatients/inpatients from the Neurology Department of Suzhou Municipal Hospital, with WMIL confirmed by brain MRI. Diagnostic features: symmetric, diffusely distributed, ill-defined lesions in periventricular and subcortical white matter; iso- or hypointense on T1WI; hyperintense on T2WI and FLAIR.
• Control group: healthy individuals aged 45-60 years with brain MRI showing no intracranial lesions.

Exclusion Criteria:

• Acute intracerebral hemorrhage or acute infarction on brain MRI or CT.
• Central nervous system diseases that severely affect cognition, such as Alzheimer's disease or frontotemporal dementia.
• White matter lesions due to other causes (e.g., toxic, genetic, immune, infectious, neoplastic, radiation-related).
• Severe hepatic, renal, or cardiac insufficiency.
• Recent major surgery or severe trauma.
• History of psychiatric disorders that would preclude completion of study scales.
• Unable to provide written informed consent.