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Background: Arterial hypertension (HTN) dramatically increases the risk for stroke and neurodegenerative disease, but signatures of macro- and microangiopathic brain damage are already visible in magnetic resonance imaging (MRI) of asymptomatic HTN patients. Blood pressure (BP) levels that initiate detrimental effects on brain tissue are still undefined. Their identification may be important for successful BP-management and prevention of subsequent cerebrovascular disease. Our objective was to test whether elevated BP relates to lower grey matter volume (GMV) in young adults who had not been diagnosed as hypertensive (≥140/90 mmHg) previously. Methods: We related BP and GMV from structural 3 Tesla T1-weighted MRI of 423 healthy adults between 19-40 years (age=27.7±5.3 years, 177 women, systolic BP (SBP)=123.2±12.2 mmHg, diastolic BP (DBP)=73.4±8.5 mmHg). Data originated from four previously unpublished cross-sectional studies conducted in Leipzig, Germany. We performed voxel-based morphometry on each study separately and combined results in image-based meta-analyses (IBMA) to assess cumulative effects across studies. Resting BP was assigned to one of four categories: (1) SBP<120 mmHg and DBP<80 mmHg, (2) SBP 120-129 mmHg or DBP 80-84 mmHg, (3) SBP 130-139 mmHg or DBP 85-89 mmHg, (4) SBP≥140 mmHg or DBP≥90 mmHg. Findings: IBMA yielded: (a) regional GMV decreased linearly as peripheral BP increased; (b) significantly decreased GMV with higher peripheral BP when comparing individuals in sub-hypertensive categories 3 and 2, respectively, to those in category 1; (c) lower BP-related GMV was found in regions including hippocampus, amygdala, thalamus, frontal and parietal structures (e.g. precuneus). Interpretation: In young adults without previously diagnosed HTN, BP≥120/80 mmHg was associated with lower GMV in regions that have previously been related to GM decline in older individuals with manifest HTN. This suggests that subtle pressure-related brain alterations might occur earlier in adulthood than previously assumed and already at sub-hypertensive BP levels.

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