Statin Therapy Protects White Matter in Cerebral Small Vessel Disease Independent of Lipid‐Lowering: Biomarker and Neuroimaging Evidence

BACKGROUND: Cerebral small vessel disease (CSVD) is characterized by white matter damage, but the roles of hyperlipidemia and statin therapy in its pathogenesis remain controversial. This study aimed to investigate the independent effects of statin therapy and hyperlipidemia on white matter integrity in CSVD patients. OBJECTIVE: To investigate the independent effects of hyperlipidemia and statin therapy on white matter damage in CSVD by examining their relationship with serum myelin basic protein (MBP) levels, Fazekas scores, and hippocampal structure. METHODS: This study recruited 141 participants from Fuyang City, China, with 71 CSVD patients and 70 NCSVD controls. Participants underwent multimodal cranial MRI, cognitive assessments, and blood tests. Statistical analyses explored the relationships between MBP levels, Fazekas scores, hippocampal fimbria volume, and statin therapy. RESULTS: Statin therapy was significantly associated with lower Fazekas scores (p = 0.018), decreased MBP levels (p = 0.006), and higher hippocampal fimbria volumes (p = 0.009 for left fimbria, p = 0.010 for right fimbria) only in the CSVD group. Hyperlipidemia and blood lipid levels showed no statistically significant associations with Fazekas scores, MBP levels, or hippocampal fimbria volumes in either group. CONCLUSION: This study demonstrates that statin therapy is independently associated with reduced white matter damage in CSVD, irrespective of peripheral lipid levels. This protective effect is specific to CSVD patients, possibly related to statin therapy improving dysregulated central nervous system lipid metabolism following blood-brain barrier dysfunction. These findings provide new insights into CSVD pathophysiology and highlight the potential of statins as a therapeutic strategy for white matter protection in CSVD.