@article {Acostasvn-2022-001929, author = {Juli{\'a}n N Acosta and Stefan P Haider and Cyprien Rivier and Audrey C Leasure and Kevin N Sheth and Guido J Falcone and Seyedmehdi Payabvash}, title = {Blood pressure-related white matter microstructural disintegrity and associated cognitive function impairment in asymptomatic adults}, elocation-id = {svn-2022-001929}, year = {2023}, doi = {10.1136/svn-2022-001929}, publisher = {BMJ Specialist Journals}, abstract = {Background and objectives We aimed to investigate the white matter (WM) microstructural/cytostructural disintegrity patterns related to higher systolic blood pressure (SBP), and whether they mediate SBP effects on cognitive performance in middle-aged adults.Methods Using the UK Biobank study of community-dwelling volunteers aged 40{\textendash}69 years, we included participants without a history of stroke, dementia, demyelinating disease or traumatic brain injury. We investigated the association of SBP with MRI diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (a measure of neurite density), isotropic (free) water volume fraction (ISOVF) and orientation dispersion across WM tracts. Then, we determined whether WM diffusion metrics mediated the effects of SBP on cognitive function.Results We analysed 31 363 participants{\textemdash}mean age of 63.8 years (SD: 7.7), and 16 523 (53\%) females. Higher SBP was associated with lower FA and neurite density, but higher MD and ISOVF. Among different WM tracts, diffusion metrics of the internal capsule anterior limb, external capsule, superior and posterior corona radiata were most affected by higher SBP. Among seven cognitive metrics, SBP levels were only associated with {\textquoteleft}fluid intelligence{\textquoteright} (adjusted p\<0.001). In mediation analysis, the averaged FA of external capsule, internal capsule anterior limb and superior cerebellar peduncle mediated 13\%, 9\% and 13\% of SBP effects on fluid intelligence, while the averaged MD of external capsule, internal capsule anterior and posterior limbs, and superior corona radiata mediated 5\%, 7\%, 7\% and 6\% of SBP effects on fluid intelligence, respectively.Discussion Among asymptomatic adults, higher SBP is associated with pervasive WM microstructure disintegrity, partially due to reduced neuronal count, which appears to mediate SBP adverse effects on fluid intelligence. Diffusion metrics of select WM tracts, which are most reflective of SBP-related parenchymal damage and cognitive impairment, may serve as imaging biomarkers to assess treatment response in antihypertensive trials.Data are available in a public, open access repository. The clinical and imaging data analysed in our study is available to researcher via the UK Biobank on completion of the registration process (see https://www.ukbiobank.ac.uk/enable-your-research/register) and on successful application (see https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access).}, issn = {2059-8688}, URL = {https://svn.bmj.com/content/early/2023/03/05/svn-2022-001929}, eprint = {https://svn.bmj.com/content/early/2023/03/05/svn-2022-001929.full.pdf}, journal = {Stroke and Vascular Neurology} }