{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:48:26Z","timestamp":1788968906473,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T00:00:00Z","timestamp":1490918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006380","name":"Rehabilitation Research and Development Service","doi-asserted-by":"publisher","award":["B9254\u2010C"],"award-info":[{"award-number":["B9254\u2010C"]}],"id":[{"id":"10.13039\/100006380","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age\u2010related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting\u2010state fMRI in a large sample of early\u2010 to mid\u2010life Veterans (<jats:italic>N<\/jats:italic>\u2009=\u2009206, Mean<jats:sub>age<\/jats:sub>\u2009=\u200932). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age\u2010related decoupling (i.e., decreased network connectivity with age), but <jats:italic>only<\/jats:italic> in participants with clinically\u2010elevated total cholesterol (\u2265180 mg\/dL). Crucially, decoupling in this network corresponded to greater day\u2010to\u2010day disability and mediated age\u2010related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age\u2010related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within\u2010module communication (indexed by Within\u2010Module Degree <jats:italic>Z<\/jats:italic>\u2010Score) and increasing between\u2010module communication (indexed by Participation Coefficient), but only in participants with clinically\u2010elevated cholesterol. Follow\u2010up analyses indicated that all findings were driven by low\u2010density lipoprotein (LDL) levels, rather than high\u2010density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. <jats:italic>Hum Brain Mapp 38:3249\u20133261, 2017<\/jats:italic>. \u00a9 <jats:bold>2017 Wiley Periodicals, Inc.<\/jats:bold><\/jats:p>","DOI":"10.1002\/hbm.23587","type":"journal-article","created":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T16:41:23Z","timestamp":1490978483000},"page":"3249-3261","source":"Crossref","is-referenced-by-count":21,"title":["Higher serum cholesterol is associated with intensified age\u2010related neural network decoupling and cognitive decline in early\u2010 to mid\u2010life"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-7157","authenticated-orcid":false,"given":"Jeffrey M.","family":"Spielberg","sequence":"first","affiliation":[{"name":"Department of Psychological and Brain Sciences University of Delaware Newark Delaware 19716"},{"name":"Neuroimaging Research for Veterans Center, VA Boston Healthcare System Boston Massachusetts 02130"},{"name":"Department of Psychiatry Boston University School of Medicine Boston Massachusetts 02130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Sadeh","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of Delaware Newark Delaware 19716"},{"name":"National Center for Posttraumatic Stress Disorder, Behavioral Sciences Division, VA Boston Healthcare System Boston Massachusetts 02130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Leritz","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education &amp; Clinical Center &amp; Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System Boston Massachusetts 02130"},{"name":"Department of Psychiatry Harvard Medical School Boston Massachusetts 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina E.","family":"McGlinchey","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education &amp; Clinical Center &amp; Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System Boston Massachusetts 02130"},{"name":"Department of Psychiatry Harvard Medical School Boston Massachusetts 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William P.","family":"Milberg","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education &amp; Clinical Center &amp; Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System Boston Massachusetts 02130"},{"name":"Department of Psychiatry Harvard Medical School Boston Massachusetts 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmeet P.","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Boston University School of Medicine Boston Massachusetts 02130"},{"name":"National Center for Posttraumatic Stress Disorder, Behavioral Sciences Division, VA Boston Healthcare System Boston Massachusetts 02130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Salat","sequence":"additional","affiliation":[{"name":"Neuroimaging Research for Veterans Center, VA Boston Healthcare System Boston Massachusetts 02130"},{"name":"Geriatric Research, Education &amp; Clinical Center &amp; Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System Boston Massachusetts 02130"},{"name":"Department of Radiology Harvard Medical School Boston Massachusetts 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