{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:05:11Z","timestamp":1793235911505,"version":"4.5.0"},"reference-count":25,"publisher":"American Diabetes Association","issue":"8","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,8,1]]},"abstract":"\n OBJECTIVE<\/jats:title>\n Diabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer\u2019s disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults.<\/jats:p>\n <\/jats:sec>\n \n RESEARCH DESIGN AND METHODS<\/jats:title>\n Framingham Offspring participants who underwent volumetric MRI and detailed cognitive testing and were free of clinical stroke and dementia during examination 7 (1998\u20132001) constituted our study sample (n = 2,439; 1,311 women; age 61 \u00b1 9 years). We related diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, and glycohemoglobin levels to cross-sectional MRI measures of total cerebral brain volume (TCBV) and hippocampal volume and to verbal and visuospatial memory and executive function. We serially adjusted for age, sex, and education alone (model A), additionally for other vascular risk factors (model B), and finally, with the inclusion of apolipoprotein E-\u03b54, plasma homocysteine, C-reactive protein, and interleukin-6 (model C).<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n We observed an inverse association between all indices of metabolic dysfunction and TCBV in all models (P &lt; 0.030). The observed difference in TCBV between participants with and without diabetes was equivalent to approximately 6 years of chronologic aging. Diabetes and elevated glycohemoglobin, HOMA-IR, and fasting insulin were related to poorer executive function scores (P &lt; 0.038), whereas only HOMA-IR and fasting insulin were inversely related to visuospatial memory (P &lt; 0.007).<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n Metabolic dysregulation, especially insulin resistance, was associated with lower brain volumes and executive function in a large, relatively healthy, middle-aged, community-based cohort.<\/jats:p>\n <\/jats:sec>","DOI":"10.2337\/dc11-0308","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T22:54:48Z","timestamp":1308351288000},"page":"1766-1770","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":117,"title":["Association of Metabolic Dysregulation With Volumetric Brain Magnetic Resonance Imaging and Cognitive Markers of Subclinical Brain Aging in Middle-Aged Adults"],"prefix":"10.2337","volume":"34","author":[{"given":"Zaldy S.","family":"Tan","sequence":"first","affiliation":[{"name":"Geriatric Research Education and Clinical Center, Veterans Administration Boston Healthcare System, Boston, Massachusetts"},{"name":"Department of Medicine, Division of Aging, Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"National Heart, Lung and Blood Institute\u2019s Framingham Heart Study, Framingham, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa S.","family":"Beiser","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute\u2019s Framingham Heart Study, Framingham, Massachusetts"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, Massachusetts"},{"name":"Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline S.","family":"Fox","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"National Heart, Lung and Blood Institute\u2019s Framingham Heart Study, Framingham, Massachusetts"},{"name":"Department of Medicine, Division of Endocrinology, Hypertension and Metabolism, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhoda","family":"Au","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute\u2019s Framingham Heart Study, Framingham, Massachusetts"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayandra J.","family":"Himali","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute\u2019s Framingham Heart Study, Framingham, Massachusetts"},{"name":"Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Debette","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"DeCarli","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California\u2013Davis, Davis, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramachandran S.","family":"Vasan","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute\u2019s Framingham Heart Study, Framingham, Massachusetts"},{"name":"Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A.","family":"Wolf","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute\u2019s Framingham Heart Study, Framingham, Massachusetts"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute\u2019s Framingham Heart Study, Framingham, Massachusetts"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2011,7,16]]},"reference":[{"key":"2022031219125223800_B1","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1001\/archneur.60.8.1119","article-title":"Alzheimer disease in the US population: prevalence estimates using the 2000 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