{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T07:51:50Z","timestamp":1769154710859,"version":"3.49.0"},"reference-count":28,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T00:00:00Z","timestamp":1595203200000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Type 2 diabetes has been associated with depression. However, the underlying pathophysiological mechanisms remain unknown. Cerebral small vessel disease, a consequence of diabetes, may lead to depression. Therefore, we evaluated whether cerebral small vessel disease mediates the association between type 2 diabetes and higher depressive symptoms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>We used longitudinal data from the population-based Age, Gene\/Environment Susceptibility (AGES)-Reykjavik Study, with examinations from 2002 to 2006 and 5 years later. Type 2 diabetes was defined as self-reported history of type 2 diabetes, use of blood glucose\u2013lowering drugs, or fasting blood glucose level \u22657.0 mmol\/L. Cerebral small vessel disease load was quantified in a composite score based on MRI-defined presence of high white matter hyperintensity volume, low total brain parenchyma volume, and subcortical infarcts, cerebral microbleeds, and large perivascular spaces. The 5-year change in the 15-item Geriatric Depression Scale score (GDS-15) was measured between baseline and follow-up.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Included were 2,135 individuals without dementia and baseline depression (baseline age 74.5 [SD 4.6] years, 1,245 women [58.3%], and 197 [9.2%] with diabetes). The GDS-15 score increased 0.4 (SD 1.6) points over time. Baseline diabetes was associated with a greater increase in the GDS-15 score (\u03b2 = 0.337; 95% CI 0.094; 0.579), adjusted for age, sex, education, and cardiovascular risk factors. Baseline cerebral small vessel disease and change of cerebral small vessel disease statistically significantly mediated a part of this association.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Type 2 diabetes is associated with a greater increase in depressive symptoms score over 5 years, and cerebral small vessel disease partly explains this association.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc19-2437","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T20:19:31Z","timestamp":1591906771000},"page":"1781-1787","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":23,"title":["Type 2 Diabetes, Change in Depressive Symptoms Over Time, and Cerebral Small Vessel Disease: Longitudinal Data of the AGES-Reykjavik Study"],"prefix":"10.2337","volume":"43","author":[{"given":"Sytze P.","family":"Rensma","sequence":"first","affiliation":[{"name":"CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre+, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas T.","family":"van Sloten","sequence":"additional","affiliation":[{"name":"CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre+, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Ding","sequence":"additional","affiliation":[{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigurdur","family":"Sigurdsson","sequence":"additional","affiliation":[{"name":"Icelandic Heart Association, K\u00f3pavogur, Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coen D.A.","family":"Stehouwer","sequence":"additional","affiliation":[{"name":"CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre+, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5696-0084","authenticated-orcid":false,"given":"Vilmundur","family":"Gudnason","sequence":"additional","affiliation":[{"name":"Icelandic Heart Association, K\u00f3pavogur, Iceland"},{"name":"Faculty of Medicine, University of Iceland, Reykjav\u00edk, Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3238-7612","authenticated-orcid":false,"given":"Lenore J.","family":"Launer","sequence":"additional","affiliation":[{"name":"Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"2022031300300419500_B1","first-page":"120","article-title":"The association between diabetes mellitus and depression","volume":"9","author":"B\u0103descu","year":"2016","journal-title":"J Med Life"},{"key":"2022031300300419500_B2","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1001\/archpsyc.1997.01830220033006","article-title":"\u2018Vascular depression\u2019 hypothesis","volume":"54","author":"Alexopoulos","year":"1997","journal-title":"Arch Gen Psychiatry"},{"key":"2022031300300419500_B3","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1176\/appi.ajp.2014.14050578","article-title":"Cerebral small vessel disease and association with higher incidence of depressive symptoms in a general elderly population: the AGES-Reykjavik Study","volume":"172","author":"van Sloten","year":"2015","journal-title":"Am J Psychiatry"},{"key":"2022031300300419500_B4","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol"},{"key":"2022031300300419500_B5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S2213-8587(14)70148-2","article-title":"Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review","volume":"3","author":"Geijselaers","year":"2015","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2022031300300419500_B6","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.neubiorev.2018.04.003","article-title":"Cerebral small vessel disease and risk of incident stroke, dementia and depression, and all-cause mortality: a systematic review and meta-analysis","volume":"90","author":"Rensma","year":"2018","journal-title":"Neurosci Biobehav Rev"},{"key":"2022031300300419500_B7","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1093\/aje\/kwk115","article-title":"Age, Gene\/Environment Susceptibility-Reykjavik Study: multidisciplinary applied phenomics","volume":"165","author":"Harris","year":"2007","journal-title":"Am J Epidemiol"},{"key":"2022031300300419500_B8","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/1753-0407.12524","article-title":"American Diabetes Association Standards of Medical Care in Diabetes 2017","volume":"9","author":"Marathe","year":"2017","journal-title":"J Diabetes"},{"key":"2022031300300419500_B9","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/(SICI)1099-1166(199910)14:10<858::AID-GPS35>3.0.CO;2-8","article-title":"Short versions of the geriatric depression scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV","volume":"14","author":"Almeida","year":"1999","journal-title":"Int J Geriatr Psychiatry"},{"key":"2022031300300419500_B10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0022-3956(82)90033-4","article-title":"Development and validation of a geriatric depression screening scale: a preliminary report","volume":"17","author":"Yesavage","year":"1982\u20131983","journal-title":"J Psychiatr Res"},{"key":"2022031300300419500_B11","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1001\/archgenpsychiatry.2011.1858","article-title":"Association of vascular factors with apathy in community-dwelling elderly individuals","volume":"69","author":"Ligthart","year":"2012","journal-title":"Arch Gen Psychiatry"},{"key":"2022031300300419500_B12","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1136\/jnnp.2007.121913","article-title":"Cerebral microbleeds in the population based AGES-Reykjavik Study: prevalence and location","volume":"79","author":"Sveinbjornsdottir","year":"2008","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2022031300300419500_B13","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1001\/jama.2009.932","article-title":"Migraine headache in middle age and late-life brain infarcts","volume":"301","author":"Scher","year":"2009","journal-title":"JAMA"},{"key":"2022031300300419500_B14","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1016\/j.neuroimage.2011.11.024","article-title":"Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik Study","volume":"59","author":"Sigurdsson","year":"2012","journal-title":"Neuroimage"},{"key":"2022031300300419500_B15","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1001\/jamaneurol.2017.1397","article-title":"Large perivascular spaces visible on magnetic resonance imaging, cerebral small vessel disease progression, and risk of dementia: the Age, Gene\/Environment Susceptibility-Reykjavik Study","volume":"74","author":"Ding","year":"2017","journal-title":"JAMA Neurol"},{"key":"2022031300300419500_B16","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1007\/s11920-013-0390-3","article-title":"The comorbidity between depression and diabetes","volume":"15","author":"Oladeji","year":"2013","journal-title":"Curr Psychiatry Rep"},{"key":"2022031300300419500_B17","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.cpr.2011.08.001","article-title":"The bidirectional relationship of depression and diabetes: a systematic review","volume":"31","author":"Renn","year":"2011","journal-title":"Clin Psychol Rev"},{"key":"2022031300300419500_B18","volume-title":"Diagnostic and Statistical Manual of Mental Disorders, DSM-IV","author":"American Psychiatric Association","year":"1994","edition":"4th ed."},{"key":"2022031300300419500_B19","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.2307\/2531158","article-title":"Procedures for comparing samples with multiple endpoints","volume":"40","author":"O\u2019Brien","year":"1984","journal-title":"Biometrics"},{"key":"2022031300300419500_B20","volume-title":"Introduction to Mediation, Moderation, and Conditional Process Analysis. A Regression-Based Approach","author":"Hayes","year":"2017"},{"key":"2022031300300419500_B21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ecl.2013.09.005","article-title":"Type 2 diabetes mellitus and hypertension: an update","volume":"43","author":"Lastra","year":"2014","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2022031300300419500_B22","first-page":"274","article-title":"Hypertension as a risk factor for developing depressive symptoms among community-dwelling elders","volume":"61","author":"Garc\u00eda-Fabela","year":"2009","journal-title":"Rev Invest Clin"},{"key":"2022031300300419500_B23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1152\/physrev.00045.2011","article-title":"Mechanisms of diabetic complications","volume":"93","author":"Forbes","year":"2013","journal-title":"Physiol Rev"},{"key":"2022031300300419500_B24","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.2337\/dbi17-0044","article-title":"Microvascular dysfunction and hyperglycemia: a vicious cycle with widespread consequences","volume":"67","author":"Stehouwer","year":"2018","journal-title":"Diabetes"},{"key":"2022031300300419500_B25","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1161\/01.CIR.88.4.1973","article-title":"Socioeconomic factors and cardiovascular disease: a review of the literature","volume":"88","author":"Kaplan","year":"1993","journal-title":"Circulation"},{"key":"2022031300300419500_B26","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/S0140-6736(06)68770-9","article-title":"Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data","volume":"367","author":"Lopez","year":"2006","journal-title":"Lancet"},{"key":"2022031300300419500_B27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nrn2294","article-title":"Glucose neurotoxicity","volume":"9","author":"Tomlinson","year":"2008","journal-title":"Nat Rev Neurosci"},{"key":"2022031300300419500_B28","first-page":"113","article-title":"Depression in diabetic patients: the relationship between mood and glycemic control","volume":"19","author":"Lustman","year":"2005","journal-title":"J Diabetes Complications"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/care.diabetesjournals.org\/syndication\/doi\/10.2337\/dc19-2437","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/43\/8\/1781\/630026\/dc192437.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/43\/8\/1781\/630026\/dc192437.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T03:47:13Z","timestamp":1647143233000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/43\/8\/1781\/35596\/Type-2-Diabetes-Change-in-Depressive-Symptoms-Over"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,11]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,6,11]]},"published-print":{"date-parts":[[2020,8,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc19-2437","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,11]]}}}