{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:17:36Z","timestamp":1792793856661,"version":"4.5.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["U01 AG006786"],"award-info":[{"award-number":["U01 AG006786"]}]},{"name":"National Institute of Health","award":["R01 NS097495"],"award-info":[{"award-number":["R01 NS097495"]}]},{"name":"National Institute of Health","award":["R01 AG056366"],"award-info":[{"award-number":["R01 AG056366"]}]},{"name":"National Institute of Health","award":["P50 AG016574"],"award-info":[{"award-number":["P50 AG016574"]}]},{"name":"National Institute of Health","award":["R37 AG011378"],"award-info":[{"award-number":["R37 AG011378"]}]},{"name":"National Institute of Health","award":["R01 AG041851"],"award-info":[{"award-number":["R01 AG041851"]}]},{"name":"National Institute of Health","award":["K76 AG057015"],"award-info":[{"award-number":["K76 AG057015"]}]},{"name":"National Institute of Health","award":["R01 AG034676"],"award-info":[{"award-number":["R01 AG034676"]}]},{"name":"Gerald and Henrietta Rauenhorst Foundation"},{"name":"Alzheimer\u2019s Drug Discovery Foundation","id":[{"id":"https:\/\/ror.org\/0185drb55","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Alexander Family Alzheimer\u2019s Disease Research Professorship of the Mayo Foundation"},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Liston Award, Elsie and Marvin Dekelboum Family Foundation","id":[{"id":"https:\/\/ror.org\/01qsat610","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Schuler Foundation"},{"name":"Opus building NIH","award":["C06 RR018898"],"award-info":[{"award-number":["C06 RR018898"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>While cerebrovascular disease can be observed in vivo using MRI, the multiplicity and heterogeneity in the mechanisms of cerebrovascular damage impede accounting for these measures in ageing and dementia studies. Our primary goal was to investigate the key sources of variability across MRI markers of cerebrovascular disease and evaluate their impact in comparison to amyloidosis on cognitive decline in a population-based sample. Our secondary goal was to evaluate the prognostic utility of a cerebrovascular summary measure from all markers. We included both visible lesions seen on MRI (white matter hyperintensities, cortical and subcortical infarctions, lobar and deep microbleeds) and early white matter damage due to systemic vascular health using diffusion changes in the genu of the corpus callosum. We identified 1089 individuals aged \u226560\u2009years with concurrent amyloid-PET and MRI scans from the population-based Mayo Clinic Study of Aging. We divided these into discovery and validation datasets. Using the discovery dataset, we conducted principal component analyses and ascertained the main sources of variability in cerebrovascular disease markers. Using linear regression and mixed effect models, we evaluated the utility of these principal components and combinations of these components for the prediction of cognitive performance along with amyloidosis. Our main findings were (i) there were three primary sources of variability among the CVD measures\u2014white matter changes are driven by white matter hyperintensities and diffusion changes; number of microbleeds (lobar and deep); and number of infarctions (cortical and subcortical); (ii) Components of white matter changes and microbleeds but not infarctions significantly predicted cognition trajectories in all domains with greater contributions from white matter; and (iii) The summary vascular score explained 3\u20135% of variability in baseline global cognition in comparison to 3\u20136% variability explained by amyloidosis. Across all cognitive domains, the vascular summary score had the least impact on memory performance (\u223c1%). Though there is mechanistic heterogeneity in the cerebrovascular disease markers measured on MRI, these changes can be grouped into three components and together explain variability in cognitive performance equivalent to the impact of amyloidosis on cognition. White matter changes represent dynamic ongoing damage, predicts future cognitive decline across all domains and diffusion measurements help capture white matter damage due to systemic vascular changes. Therefore, measuring and accounting for white matter changes using diffusion MRI and white matter hyperintensities along with microbleeds will allow us to capture vascular contributions to cognitive impairment and dementia.<\/jats:p>","DOI":"10.1093\/braincomms\/fcab076","type":"journal-article","created":{"date-parts":[[2021,4,10]],"date-time":"2021-04-10T07:49:59Z","timestamp":1618040999000},"source":"Crossref","is-referenced-by-count":48,"title":["White matter abnormalities are key components of cerebrovascular disease impacting cognitive decline"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4286-0589","authenticated-orcid":false,"given":"Prashanthi","family":"Vemuri","sequence":"first","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2770-0691","authenticated-orcid":false,"given":"Jonathan","family":"Graff-Radford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G","family":"Lesnick","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A","family":"Przybelski","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert I","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Information Technology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashritha L","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val J","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7177-1185","authenticated-orcid":false,"given":"Michelle M","family":"Mielke","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M","family":"Machulda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry\/Psychology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald C","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Knopman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Clifford R","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"issue":"24","key":"2021070810514151200_fcab076-B1","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1212\/01.wnl.0000271090.28148.24","article-title":"Mixed brain pathologies account for most dementia cases in 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