{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:01:52Z","timestamp":1791478912690,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T00:00:00Z","timestamp":1508976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS097495"],"award-info":[{"award-number":["R01 NS097495"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG56366"],"award-info":[{"award-number":["R01 AG56366"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG06786"],"award-info":[{"award-number":["U01 AG06786"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 AG16574\/P1"],"award-info":[{"award-number":["P50 AG16574\/P1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 AG16574"],"award-info":[{"award-number":["P50 AG16574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG11378"],"award-info":[{"award-number":["R01 AG11378"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG41851"],"award-info":[{"award-number":["R01 AG41851"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["C06 RR018898"],"award-info":[{"award-number":["C06 RR018898"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P50 AG16574"],"award-info":[{"award-number":["P50 AG16574"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P50 AG16574\/P1"],"award-info":[{"award-number":["P50 AG16574\/P1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG11378"],"award-info":[{"award-number":["R01 AG11378"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG41851"],"award-info":[{"award-number":["R01 AG41851"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG56366"],"award-info":[{"award-number":["R01 AG56366"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01 AG06786"],"award-info":[{"award-number":["U01 AG06786"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS097495"],"award-info":[{"award-number":["NS097495"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We identified 430 individuals along the cognitive continuum aged &gt;60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population\u2010based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence\/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC\u2010tau) from tau\u2010PET, and neurodegeneration in AD signature regions from MRI and FDG\u2010PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC\n                      <jats:sup>\u2212<\/jats:sup>\n                      ) versus CMC &gt; 0 (CMC\n                      <jats:sup>+<\/jats:sup>\n                      ) and tested for age\u2010adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CMC\n                      <jats:sup>+<\/jats:sup>\n                      participants had significantly greater neurodegeneration than CMC\n                      <jats:sup>\u2212<\/jats:sup>\n                      participants but did not differ by amyloid or ERC\u2010tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC\u2010tau.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706\u2013718<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25071","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T14:39:16Z","timestamp":1507646356000},"page":"706-718","source":"Crossref","is-referenced-by-count":168,"title":["Age, vascular health, and Alzheimer disease biomarkers in an elderly sample"],"prefix":"10.1002","volume":"82","author":[{"given":"Prashanthi","family":"Vemuri","sequence":"first","affiliation":[{"name":"Department of Radiology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Lesnick","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Przybelski","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Knopman","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val J.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Graff\u2010Radford","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosebud O.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Mielke","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic Rochester MN"},{"name":"Department of Neurology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Machulda","sequence":"additional","affiliation":[{"name":"Department of Psychology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald C.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Clifford R.","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic Rochester MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,26]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0594.2010.00603.x"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000341271.90478.8e"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0718-6"},{"key":"e_1_2_1_6_1","first-page":"1","article-title":"Vascular risk factors and Alzheimer's disease: are these risk factors for plaques and tangles or for concomitant vascular pathology that increases the likelihood of dementia? An evidence\u2010based review","volume":"4","author":"Chui HC","year":"2012","journal-title":"Alzheimers Res Ther"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.4.643"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.322.7300.1447"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.007847"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000550"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn016"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0315-6"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv283"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2012.08.012"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys195"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f11d85"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000115751"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.13612"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2014.07.010"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glx026"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.005"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2016.12.010"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2014.02.004"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e8e8b8"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S37929"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/10705511.2016.1154793"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2015.03.013"},{"key":"e_1_2_1_29_1","volume-title":"Harrison's principles of internal medicine","author":"Ferrucci L","year":"2012"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90638-6"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24271"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003748"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.07.078"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.0244"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0381021"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31819ac3cb"},{"key":"e_1_2_1_38_1","first-page":"1864","article-title":"Inhibition of tau hyperphosphorylation and beta amyloid production in rat brain by oral administration of atorvastatin","volume":"123","author":"Lu F","year":"2010","journal-title":"Chin Med J (Engl)"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000277657.95487.1c"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2006-10408"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1349-0"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3230"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.01.002"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.27"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.62.10.1556"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.2174\/15672050113109990037"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002624"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.09.013"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e318231d535"},{"key":"e_1_2_1_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.25.12.2348"},{"key":"e_1_2_1_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLR.0b013e3181589b92"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(02)00390-6"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.10.050"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.25071","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T23:12:09Z","timestamp":1696029129000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.25071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,26]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1002\/ana.25071"],"URL":"https:\/\/doi.org\/10.1002\/ana.25071","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,26]]}}}