Intraocular pressure, systemic blood pressure, and brain volumes: observational and Mendelian Randomization analyses

Abstract Background It is unclear whether brain volumes are causally affected by Intraocular pressure (IOP) is highly correlated with blood pressure (BP). Methods The study included 8634 participants for IOP and 36069 participants for BP in observational analyses and 37410 participants for both IOP and BP in Mendelian Randomisation (MR) analyses from UK Biobank. IOP and BP were measured between 2006–2010. Brain volumes were measured using MRI between 2014–2019. Results Higher IOP was associated with smaller volumes of total brain (β (95% CI) for each 5-mmHg increment: -3.24 (-5.05, -1.44) ml) and grey matter (-1.10 (-2.17, -0.03) ml) independent of BP. Diastolic BP (β (95% CI) for each 10-mmHg increment: 0.13 (0.05, 0.21)) was associated with higher white matter hyperintensity (WMH) independent of antihypertensive medications. Associations between IOP and total brain and WMH volumes were stronger in younger individuals or those without hypertension. Associations between DBP/SBP and brain volumes were stronger in younger individuals, women, and lowly educated individuals. All MR analytic methods demonstrated a significant relationship between DBP and WMH (β (95% CI) for each 10-mmHg increment of DBP for inverse-variance weighting method: 0.019 (0.013, 0.026)). The β (95% CI) for grey matter volume (ml) associated with each 5-mmHg increment of IOP for inverse-variance weighting method was − 3.42 (-5.39, -1.45). Conclusions Higher IOP is casually linked to larger grey matter volume reduction while increased DBP casually linked to higher WMH load. Younger or lowly educated individuals deserve more scrutiny for the prevention of brain volume reduction potentially via IOP/DBP lowering.