{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:27:34Z","timestamp":1793284054086,"version":"4.5.0"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"am","delay-in-days":316,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Gerontology"],"published-print":{"date-parts":[[2022,9]]},"DOI":"10.1016\/j.exger.2022.111890","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T12:19:36Z","timestamp":1657801176000},"page":"111890","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Metformin use and brain atrophy in nondemented elderly individuals with diabetes"],"prefix":"10.1016","volume":"166","author":[{"given":"Fardin","family":"Nabizadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Berchi","family":"Kankam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Balabandian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedeh Melika","family":"Hashemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Sharifkazemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Rostami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exger.2022.111890_bb0005","doi-asserted-by":"crossref","DOI":"10.1177\/1533317519899546","article-title":"Antidiabetic drugs for the risk of alzheimer disease in patients with type 2 DM using FAERS","volume":"35","author":"Akimoto","year":"2020","journal-title":"Am. J. Alzheimers Dis. Other Dement."},{"issue":"3","key":"10.1016\/j.exger.2022.111890_bb0010","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrneurol.2017.185","article-title":"Brain insulin resistance in type 2 diabetes and alzheimer disease: concepts and conundrums","volume":"14","author":"Arnold","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.exger.2022.111890_bb0015","series-title":"Antidiabetic Therapies and Alzheimer Disease","first-page":"83","volume":"21(1)","author":"Bendlin","year":"2019"},{"issue":"4","key":"10.1016\/j.exger.2022.111890_bb0020","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.3233\/JAD-180263","article-title":"Metformin use associated with reduced risk of dementia in patients with diabetes: a systematic review and meta-analysis","volume":"65","author":"Campbell","year":"2018","journal-title":"J. Alzheimers Dis."},{"issue":"10","key":"10.1016\/j.exger.2022.111890_bb0025","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/dom.13373","article-title":"Comparative efficacy and acceptability of antidiabetic agents for Alzheimer's disease and mild cognitive impairment: a systematic review and network meta-analysis","volume":"20","author":"Cao","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"10.1016\/j.exger.2022.111890_bb0030","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.irn.2020.02.010","article-title":"Antidiabetic drugs for Alzheimer's and Parkinson's diseases: repurposing insulin, metformin, and thiazolidinediones","volume":"155","author":"Cardoso","year":"2020","journal-title":"Int. Rev. Neurobiol."},{"issue":"6","key":"10.1016\/j.exger.2022.111890_bb0035","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1007\/s00415-018-9016-3","article-title":"Magnetic resonance imaging in Alzheimer's disease and mild cognitive impairment","volume":"266","author":"Chandra","year":"2019","journal-title":"J. Neurol."},{"key":"10.1016\/j.exger.2022.111890_bb0040","series-title":"Antidiabetic Drug Metformin (GlucophageR) Increases Biogenesis of Alzheimer's Amyloid Peptides via Up-regulating BACE1 Transcription","first-page":"3907","volume":"106(10)","author":"Chen","year":"2009"},{"issue":"1","key":"10.1016\/j.exger.2022.111890_bb0045","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3233\/JAD-141332","article-title":"Metformin treatment alters memory function in a mouse model of Alzheimer's disease","volume":"44","author":"DiTacchio","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.exger.2022.111890_bb0050","series-title":"Higher Atrophy Rate of Entorhinal Cortex Than Hippocampus in AD","first-page":"422","volume":"62(3)","author":"Du","year":"2004"},{"key":"10.1016\/j.exger.2022.111890_bb0055","series-title":"Pattern and Progression of White-matter Changes in a Case of Posterior Cortical Atrophy Using Diffusion Tensor Imaging","first-page":"432","volume":"80(4)","author":"Duning","year":"2009"},{"key":"10.1016\/j.exger.2022.111890_bb0060","series-title":"Prediction of Alzheimer's Disease in Subjects With Mild Cognitive Impairment From the ADNI Cohort Using Patterns of Cortical Thinning","first-page":"511","volume":"65","author":"Eskildsen","year":"2013"},{"issue":"6","key":"10.1016\/j.exger.2022.111890_bb0065","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/jdi.12087","article-title":"Diabetes mellitus and risk of dementia: a meta-analysis of prospective observational studies","volume":"4","author":"Gudala","year":"2013","journal-title":"J. Diabetes Investig."},{"issue":"7715","key":"10.1016\/j.exger.2022.111890_bb0070","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1038\/d41586-018-05717-6","article-title":"Alzheimer's disease","volume":"559","author":"Hodson","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.exger.2022.111890_bb0075","series-title":"Incidence of Dementia is Increased in Type 2 Diabetes and Reduced by the Use of Sulfonylureas and Metformin","first-page":"485","volume":"24(3)","author":"Hsu","year":"2011"},{"key":"10.1016\/j.exger.2022.111890_bb0080","series-title":"Metformin, Other Antidiabetic Drugs, and Risk of Alzheimer's Disease: A Population-based Case\u2013control Study","first-page":"916","volume":"60(5)","author":"Imfeld","year":"2012"},{"key":"10.1016\/j.exger.2022.111890_bb0085","series-title":"Distribution of Alzheimer's Neurofibrillary Tangles in the Basal Ganglia and Brain Stem of Progressive Supranuclear Palsy and Alzheimer's Disease","first-page":"179","volume":"29(2)","author":"Ishino","year":"1975"},{"key":"10.1016\/j.exger.2022.111890_bb0090","series-title":"Comparison of Different MRI Brain Atrophy Rate Measures With Clinical Disease Progression in AD","first-page":"591","volume":"62(4)","author":"Jack","year":"2004"},{"key":"10.1016\/j.exger.2022.111890_bb0095","series-title":"4D Deformation Modeling of Cortical Disease Progression in Alzheimer's Dementia","first-page":"661","volume":"46(4)","author":"Janke","year":"2001"},{"key":"10.1016\/j.exger.2022.111890_bb0100","series-title":"Neuroimaging in Alzheimer Disease: An Evidence-based Review","first-page":"197","volume":"13(2)","author":"Kantarci","year":"2003"},{"issue":"9","key":"10.1016\/j.exger.2022.111890_bb0105","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1474-4422(20)30231-3","article-title":"Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches","volume":"19","author":"Kellar","year":"2020","journal-title":"Lancet Neurol."},{"issue":"2","key":"10.1016\/j.exger.2022.111890_bb0110","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/WAD.0000000000000202","article-title":"Effects of the insulin sensitizer metformin in alzheimer disease: pilot data from a randomized placebo-controlled crossover study","volume":"31","author":"Koenig","year":"2017","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"10.1016\/j.exger.2022.111890_bb0115","series-title":"Psychiatry B. Effects of Metformin Exposure on Neurodegenerative Diseases in Elderly Patients With Type 2 Diabetes Mellitus","first-page":"77","volume":"79","author":"Kuan","year":"2017"},{"key":"10.1016\/j.exger.2022.111890_bb0120","series-title":"Disease-specific Patterns of Cortical and Subcortical Degeneration in a Longitudinal Study of Alzheimer's Disease and Behavioural-variant Frontotemporal Dementia","first-page":"72","volume":"151","author":"Landin-Romero","year":"2017"},{"issue":"1","key":"10.1016\/j.exger.2022.111890_bb0125","doi-asserted-by":"crossref","first-page":"11258","DOI":"10.1038\/s41598-018-29295-9","article-title":"Structural brain imaging in Alzheimer's disease and mild cognitive impairment: biomarker analysis and shared morphometry database","volume":"8","author":"Ledig","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exger.2022.111890_bb0130","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fnagi.2018.00227","article-title":"Evaluation of metformin on cognitive improvement in patients with non-dementia vascular cognitive impairment and abnormal glucose metabolism","volume":"10","author":"Lin","year":"2018","journal-title":"Front. Aging Neurosci."},{"issue":"12","key":"10.1016\/j.exger.2022.111890_bb0135","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1007\/s11095-017-2199-y","article-title":"Metformin - a future therapy for neurodegenerative diseases : theme: drug discovery, development and delivery in Alzheimer's disease guest editor: davide brambilla","volume":"34","author":"Markowicz-Piasecka","year":"2017","journal-title":"Pharm. Res."},{"issue":"5","key":"10.1016\/j.exger.2022.111890_bb0140","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1159\/000510677","article-title":"Antidiabetic drugs in Alzheimer's disease and mild cognitive impairment: a systematic review","volume":"49","author":"Mu\u00f1oz-Jim\u00e9nez","year":"2020","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"10.1016\/j.exger.2022.111890_bb0145","series-title":"Long-term Metformin Usage and Cognitive Function Among Older Adults With Diabetes","first-page":"61","volume":"41(1)","author":"Ng","year":"2014"},{"key":"10.1016\/j.exger.2022.111890_bb0150","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.bbi.2017.12.009","article-title":"Metformin treatment prevents amyloid plaque deposition and memory impairment in APP\/PS1 mice","volume":"69","author":"Ou","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.exger.2022.111890_bb0155","series-title":"Alzheimer's Disease Neuroimaging Initiative (ADNI): Clinical Characterization","first-page":"201","volume":"74(3)","author":"Petersen","year":"2010"},{"key":"10.1016\/j.exger.2022.111890_bb0160","series-title":"Neuroimaging and Early Diagnosis of Alzheimer Disease: A Look to the Future","first-page":"315","volume":"226(2)","author":"Petrella","year":"2003"},{"issue":"8","key":"10.1016\/j.exger.2022.111890_bb0165","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.18632\/aging.101004","article-title":"Biological and biophysics aspects of metformin-induced effects: cortex mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar aggregates","volume":"8","author":"Picone","year":"2016","journal-title":"Aging"},{"issue":"1","key":"10.1016\/j.exger.2022.111890_bb0170","doi-asserted-by":"crossref","DOI":"10.1136\/bmjdrc-2020-001370","article-title":"Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis","volume":"8","author":"Ping","year":"2020","journal-title":"BMJ Open Diabetes Res. Care"},{"issue":"1","key":"10.1016\/j.exger.2022.111890_bb0175","article-title":"Loss of corneal nerves and brain volume in mild cognitive impairment and dementia","volume":"8","author":"Ponirakis","year":"2022","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.exger.2022.111890_bb0180","series-title":"Intranasal Insulin Improves Cognition and Modulates \u03b2-amyloid in Early AD","first-page":"440","volume":"70(6)","author":"Reger","year":"2008"},{"key":"10.1016\/j.exger.2022.111890_bb0185","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3389\/fnagi.2015.00199","article-title":"The roles of lipid and glucose metabolism in modulation of \u03b2-amyloid, tau, and neurodegeneration in the pathogenesis of alzheimer disease","volume":"7","author":"Sato","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.exger.2022.111890_bb0190","series-title":"JNK Activation is Associated With Intracellular \u03b2-amyloid Accumulation","first-page":"221","volume":"85(1-2)","author":"Shoji","year":"2000"},{"key":"10.1016\/j.exger.2022.111890_bb0195","series-title":"Clearance Systems in the Brain\u2014Implications for Alzheimer Disease","first-page":"457","volume":"11(8)","author":"Tarasoff-Conway","year":"2015"},{"issue":"1","key":"10.1016\/j.exger.2022.111890_bb0200","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00415-020-10109-w","article-title":"Cortical diffusivity investigation in posterior cortical atrophy and typical Alzheimer's disease","volume":"268","author":"Torso","year":"2021","journal-title":"J. Neurol."},{"key":"10.1016\/j.exger.2022.111890_bb0205","series-title":"Preserved Cognition in Patients With Early Alzheimer Disease and Amnestic Mild Cognitive Impairment During Treatment With Rosiglitazone: A Preliminary Study","first-page":"950","volume":"13(11)","author":"Watson","year":"2005"},{"issue":"Pt 1","key":"10.1016\/j.exger.2022.111890_bb0210","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/brain\/awr277","article-title":"Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease","volume":"135","author":"Weintraub","year":"2012","journal-title":"Brain"}],"container-title":["Experimental Gerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S053155652200198X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S053155652200198X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T03:39:50Z","timestamp":1759981190000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S053155652200198X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":42,"alternative-id":["S053155652200198X"],"URL":"https:\/\/doi.org\/10.1016\/j.exger.2022.111890","relation":{},"ISSN":["0531-5565"],"issn-type":[{"value":"0531-5565","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Metformin use and brain atrophy in nondemented elderly individuals with diabetes","name":"articletitle","label":"Article Title"},{"value":"Experimental Gerontology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exger.2022.111890","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"111890"}}