Effects of Higher Normal Blood Pressure on Brain Are Detectable before Middle‐Age and Differ by Sex

Background: To quantify the association between blood pressure (BP) across its full range, brain volumes and white matter lesions (WMLs) while investigating the effects of age, sex, body mass index (BMI), and antihypertensive medication. Methods: UK Biobank participants (n = 36,260) aged (40–70) years were included and stratified by sex and four age groups (age ≤ 45, 46–55, 56–65 and > 65 years). Multi‐level regression analyses were used to assess the association between mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP), and brain volumes segmented using the FreeSufer software (gray matter volume [GMV], white matter volume [WMV], left [LHCV] and right hippocampal volume [RHCV]) and WMLs. Interaction effects between body mass index (BMI), antihypertensive medication and BP in predicting brain volumes and WMLs were also investigated. Results: Every 10 mmHg higher DBP was associated with lower brain volumes (GMV: −0.19%– −0.40%) [SE = 47.7–62.4]; WMV: −0.20–−0.23% [SE = 34.66–53.03]; LHCV: −0.40–−0.59% [SE = 0.44– 0.57]; RHCV: −0.17–−0.57% [SE = 0.32–0.95]) across all age groups. A similar pattern was detected in both sexes, although it was weaker in men. Every 10 mmHg higher MAP was associated with larger WMLs across all age groups but peaked >65 years (1.19–1.23% [SE = 0.002]). Both lower BMI and anti‐hypertensive medication appeared to afford a protective effect. Conclusion: Higher BP is associated with worse cerebral health across the full BP range from middle adulthood and into old age.