Abstract WP65: Inflammatory Biomarkers and Progression of MRI-Visible Perivascular Spaces: Findings from The Framingham Heart Study

Introduction: Perivascular Spaces (PVS) visible on brain magnetic resonance imaging (MRI) are markers of Cerebral Small Vessel Disease (CSVD). Recent evidence suggests a potential role of inflammatory biomarkers in the pathogenesis of PVS. This study aimed to examine the relation between inflammation markers and progression of PVS burden in community-dwelling individuals. Methods: Offspring Framingham Heart Study participants with available inflammatory biomarkers at exam 7 and MRI-PVS assessments at exams 7 and 8 were included. Sixteen components of the inflammatory cascade were analyzed at baseline. PVS were rated as low PVS burden (grade I-II) and high PVS burden (grade III-IV) separately in the Basal Ganglia (BG) and Centrum Semiovale (CSO), using a validated method. Progression in PVS burden between exams 7 and 8 were categorized as change (low to high burden) vs no change. Multivariable logistic regression models were used to assess the association between individual inflammatory biomarkers and changes in MRI-PVS burden. Model 1 was adjusted for age and sex, and Model 2 was additionally adjusted for smoking (SMK), diabetes (DM), hypertension (HTN), prevalent cardiovascular disease (CVD), body mass index and apoE4. Results: Among 561 participants (mean age 61.12 ± 8.85 years, 48% male) with an overall low prevalence of vascular risk factors (HTN 37 %, DM 11,15%, SMK 10,87%, CVD 10.34%) we observed that Osteoprotegerin (OPG) levels (mean 5.40 pmol/L ± 1.62) were associated with increase in PVS burden in BG (OR 1.43 [1.08, 1.88] p = 0.01) and CSO (OR 1.32 [1.07, 1.62] p = 0.008). Further adjustment for vascular risk factors did not change this association. No other significant associations were observed. Conclusion: In community dwelling individuals free of stroke and dementia with a low prevalence of vascular risk factors, the inflammatory marker OPG was associated with progression of PVS burden in BG and CSO. Further research is needed to elucidate the specific mechanism behind this association and the potential role of OPG as treatment target to mitigate the inflammatory processes contributing to PVS and its adverse consequences.