{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:27:37Z","timestamp":1774956457945,"version":"3.50.1"},"reference-count":40,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>While the apolipoprotein E \u03b54 allele (ApoE-\u03b54) is related to cognitive and brain decline in the general population, its effect on the brain in type 1 diabetes mellitus (T1DM) remains unclear. Therefore, the aim was to determine the interaction between ApoE-\u03b54 and T1DM on cognitive performance and hippocampal structure and connectivity as the brain area most vulnerable to ApoE-\u03b54 effects in adult patients with T1DM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Blood sampling was performed in 104 patients with T1DM and 49 control subjects for ApoE genotyping, neuropsychology, and neuroimaging to determine hippocampal volume and resting-state connectivity. The interaction between T1DM status and ApoE-\u03b54 presence was investigated and adjusted for age and mean systolic blood pressure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>ApoE genotyping could not be performed for three patients with T1DM. Significant interaction effects, indicating a differential effect of ApoE-\u03b54 between both groups, were found for overall cognitive functioning and for the subdomains of information processing speed and attention. Additionally, interaction effects were present for right hippocampal connectivity with the right posterior cingulate and supramarginal gyri. Subsequent group analysis showed that patients with T1DM with ApoE-\u03b54 performed worse on these cognitive domains with increased connectivity, relative to their counterparts without ApoE-\u03b54. In contrast, no cognitive effects, but decreased connectivity, were observed in control subjects with ApoE-\u03b54. In patients with T1DM, higher right hippocampus connectivity with the posterior cingulate gyrus was related to poorer overall cognitive functioning.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>The results may suggest that ApoE-\u03b54 presence leaves our patients with T1DM more susceptible to cognitive decrements at a younger age, possibly through vascular pathways, warranting further longitudinal studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc21-0483","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T17:00:27Z","timestamp":1628701227000},"page":"2388-2396","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":2,"title":["Cognitive Functioning and Hippocampal Connectivity in Patients With Longstanding Type 1 Diabetes and Apolipoprotein E \u03b54"],"prefix":"10.2337","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0558-9435","authenticated-orcid":false,"given":"Eelco","family":"van Duinkerken","sequence":"first","affiliation":[{"name":"Department of Medical Psychology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Amsterdam Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Instituto Estadual do C\u00e9rebro Paulo Niemeyer, Center for Epilepsy, Rio de Janeiro, RJ, Brazil"},{"name":"Department of Neurology, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard G.","family":"IJzerman","sequence":"additional","affiliation":[{"name":"Amsterdam Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Institute of Neurology and Healthcare Engineering, University College London, London, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette C.","family":"Moll","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Diamant","sequence":"additional","affiliation":[{"name":"Amsterdam Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J.","family":"Snoek","sequence":"additional","affiliation":[{"name":"Department of Medical Psychology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Department of Medical Psychology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Medical Psychology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"2022031309344795000_B1","doi-asserted-by":"crossref","first-page":"104608","DOI":"10.1016\/j.nbd.2019.104608","article-title":"Diabetes mellitus in the young and the old: effects on cognitive functioning across the life span","volume":"134","author":"van Duinkerken","year":"2020","journal-title":"Neurobiol Dis"},{"key":"2022031309344795000_B2","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1007\/s00125-015-3515-x","article-title":"Risk of dementia in patients hospitalised with type 1 and type 2 diabetes in England, 1998-2011: a retrospective national record linkage cohort study","volume":"58","author":"Smolina","year":"2015","journal-title":"Diabetologia"},{"key":"2022031309344795000_B3","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1017\/S2045796019000374","article-title":"Risk of dementia and cognitive dysfunction in individuals with diabetes or elevated blood glucose","volume":"29","author":"Wium-Andersen","year":"2019","journal-title":"Epidemiol Psychiatr Sci"},{"key":"2022031309344795000_B4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"2022031309344795000_B5","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis","volume":"278","author":"Farrer","year":"1997","journal-title":"JAMA"},{"key":"2022031309344795000_B6","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/418932a","article-title":"Cognitive change and the APOE epsilon 4 allele","volume":"418","author":"Deary","year":"2002","journal-title":"Nature"},{"key":"2022031309344795000_B7","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.neurobiolaging.2006.10.030","article-title":"Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E epsilon 4","volume":"29","author":"Espeseth","year":"2008","journal-title":"Neurobiol Aging"},{"key":"2022031309344795000_B8","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.neuroimage.2008.03.039","article-title":"Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers","volume":"41","author":"Burggren","year":"2008","journal-title":"Neuroimage"},{"key":"2022031309344795000_B9","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.bbadis.2008.10.013","article-title":"A look inside the diabetic brain: contributors to diabetes-induced brain aging","volume":"1792","author":"Wrighten","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"2022031309344795000_B10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.17925\/EE.2014.10.01.14","article-title":"Hippocampal volume in type 1 diabetes","volume":"10","author":"Murray","year":"2014","journal-title":"Eur Endocrinol"},{"key":"2022031309344795000_B11","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.neulet.2012.02.031","article-title":"Association between apolipoprotein E gene polymorphism and the risk of vascular dementia: a meta-analysis","volume":"514","author":"Yin","year":"2012","journal-title":"Neurosci Lett"},{"key":"2022031309344795000_B12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1464-5491.2009.02885.x","article-title":"The associations of apolipoprotein E and angiotensin-converting enzyme polymorphisms and cognitive function in Type 1 diabetes based on an 18-year follow-up of the DCCT cohort","volume":"27","author":"Jacobson","year":"2010","journal-title":"Diabet Med"},{"key":"2022031309344795000_B13","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2337\/diabetes.52.1.145","article-title":"Apolipoprotein-E influences aspects of intellectual ability in type 1 diabetes","volume":"52","author":"Ferguson","year":"2003","journal-title":"Diabetes"},{"key":"2022031309344795000_B14","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/BF00410281","article-title":"Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM complications study","volume":"38","author":"Aldington","year":"1995","journal-title":"Diabetologia"},{"key":"2022031309344795000_B15","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.2337\/db11-1358","article-title":"Resting-state brain networks in type 1 diabetic patients with and without microangiopathy and their relation to cognitive functions and disease variables","volume":"61","author":"van Duinkerken","year":"2012","journal-title":"Diabetes"},{"key":"2022031309344795000_B16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.7326\/0003-4819-124-4-199602150-00001","article-title":"Effects of intensive diabetes therapy on neuropsychological function in adults in the Diabetes Control and Complications Trial","volume":"124","author":"The Diabetes Control Complications Trial Research Group","year":"1996","journal-title":"Ann Intern Med"},{"key":"2022031309344795000_B17","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1097\/PSY.0000000000000335","article-title":"Subgenual cingulate cortex functional connectivity in relation to depressive symptoms and cognitive functioning in type 1 diabetes mellitus patients","volume":"78","author":"van Duinkerken","year":"2016","journal-title":"Psychosom Med"},{"key":"2022031309344795000_B18","volume-title":"Nederlandse Leeslijst Volwassenen: Handleiding","author":"Schmand","year":"1992"},{"key":"2022031309344795000_B19","first-page":"13","article-title":"New version of 15 words test (15WTA and 15 WTB)","volume-title":"Neuropsychological Diagnostics Handbook","author":"Saan","year":"1986"},{"key":"2022031309344795000_B20","volume-title":"Wechsler Adult Intelligence Scale Manual","author":"Wechsler","year":"1955"},{"key":"2022031309344795000_B21","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1037\/1040-3590.18.4.424","article-title":"The Concept Shifting Test: adult normative data","volume":"18","author":"Van der Elst","year":"2006","journal-title":"Psychol Assess"},{"key":"2022031309344795000_B22","volume-title":"Stroop Color Word Test: A Manual for Clinical End Experimental Uses","author":"Golden","year":"1978"},{"key":"2022031309344795000_B23","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1111\/j.1528-1157.1990.tb05868.x","article-title":"Computerized neuropsychological assessment of cognitive functioning in children with epilepsy","volume":"31","author":"Alpherts","year":"1990","journal-title":"Epilepsia"},{"key":"2022031309344795000_B24","volume-title":"Aufmerksamkeits-Belastungs-Test (Test D2)","author":"Brickenkamp","year":"1962"},{"key":"2022031309344795000_B25","volume-title":"Wisconsin Cart Sorting Test Manual: Revised and Expanded (WCTS)","author":"Heaton","year":"1993"},{"key":"2022031309344795000_B26","volume-title":"Primary Mental Abilities","author":"Thurstone","year":"1962"},{"key":"2022031309344795000_B27","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1080\/13803390591004428","article-title":"The Letter Digit Substitution Test: normative data for 1,858 healthy participants aged 24-81 from the Maastricht Aging Study (MAAS): influence of age, education, and sex","volume":"28","author":"van der Elst","year":"2006","journal-title":"J Clin Exp Neuropsychol"},{"key":"2022031309344795000_B28","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2337\/db09-0653","article-title":"A genome-wide association study identifies a novel major locus for glycemic control in type 1 diabetes, as measured by both A1C and glucose","volume":"59","author":"Paterson","year":"2010","journal-title":"Diabetes"},{"key":"2022031309344795000_B29","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.neuroimage.2015.02.064","article-title":"ICA-AROMA: a robust ICA-based strategy for removing motion artifacts from fMRI data","volume":"112","author":"Pruim","year":"2015","journal-title":"Neuroimage"},{"key":"2022031309344795000_B30","doi-asserted-by":"crossref","first-page":"7900","DOI":"10.1073\/pnas.1602413113","article-title":"Cluster failure: why fMRI inferences for spatial extent have inflated false-positive rates","volume":"113","author":"Eklund","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022031309344795000_B31","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.3233\/JAD-2010-091198","article-title":"Joint effect of hypertension and APOE genotype on CSF biomarkers for Alzheimer\u2019s disease","volume":"20","author":"Kester","year":"2010","journal-title":"J Alzheimers Dis"},{"key":"2022031309344795000_B32","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.2337\/dc13-1586","article-title":"Proliferative retinopathy in type 1 diabetes is associated with cerebral microbleeds, which is part of generalized microangiopathy","volume":"37","author":"Woerdeman","year":"2014","journal-title":"Diabetes Care"},{"key":"2022031309344795000_B33","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1007\/s00125-014-3333-6","article-title":"Cerebrospinal fluid levels of Alzheimer\u2019s disease biomarkers in middle-aged patients with type 1 diabetes","volume":"57","author":"Ouwens","year":"2014","journal-title":"Diabetologia"},{"key":"2022031309344795000_B34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jdiacomp.2018.04.003","article-title":"Clinically significant cognitive impairment in older adults with type 1 diabetes","volume":"33","author":"Chaytor","year":"2019","journal-title":"J Diabetes Complications"},{"key":"2022031309344795000_B35","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.2337\/db12-1159","article-title":"Cerebral blood flow and glucose metabolism measured with positron emission tomography are decreased in human type 1 diabetes","volume":"62","author":"van Golen","year":"2013","journal-title":"Diabetes"},{"key":"2022031309344795000_B36","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fnagi.2018.00180","article-title":"APOE and Alzheimer\u2019s disease: neuroimaging of metabolic and cerebrovascular dysfunction","volume":"10","author":"Brandon","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"2022031309344795000_B37","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1146\/annurev-neuro-071013-014030","article-title":"The brain\u2019s default mode network","volume":"38","author":"Raichle","year":"2015","journal-title":"Annu Rev Neurosci"},{"key":"2022031309344795000_B38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3389\/fnagi.2018.00289","article-title":"Apolipoprotein E \u03b54 specifically modulates the hippocampus functional connectivity network in patients with amnestic mild cognitive impairment","volume":"10","author":"Zhu","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"2022031309344795000_B39","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2174\/1567205014666170206113528","article-title":"ApoE \u03b54 allele related alterations in hippocampal connectivity in early Alzheimer\u2019s disease support memory performance","volume":"14","author":"De Marco","year":"2017","journal-title":"Curr Alzheimer Res"},{"key":"2022031309344795000_B40","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1212\/WNL.0b013e3181db9957","article-title":"The limits of functional reorganization in multiple sclerosis","volume":"74","author":"Schoonheim","year":"2010","journal-title":"Neurology"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/44\/10\/2388\/632259\/dc210483.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/44\/10\/2388\/632259\/dc210483.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T10:45:56Z","timestamp":1647168356000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/44\/10\/2388\/138522\/Cognitive-Functioning-and-Hippocampal-Connectivity"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,11]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,8,11]]},"published-print":{"date-parts":[[2021,10,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc21-0483","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,11]]}}}