{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:40:21Z","timestamp":1790617221929,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore Ministry of Health\u2019s National Medical Research Council","award":["NMRC\/TA\/0008\/2012"],"award-info":[{"award-number":["NMRC\/TA\/0008\/2012"]}]},{"name":"Singapore Ministry of Health\u2019s National Medical Research Council","award":["NMRC\/STaR\/0003\/2008"],"award-info":[{"award-number":["NMRC\/STaR\/0003\/2008"]}]},{"name":"Biomedical Research Council (BMRC), Singapore","award":["08\/1\/35\/19\/550"],"award-info":[{"award-number":["08\/1\/35\/19\/550"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The role of leptin (a hormone related to fat mass) in cognition remains equivocal. Our objective was to investigate the relationship between circulating leptin concentration and cognition in older adults, accounting for potential confounders. We categorized 1061 community-dwelling older participants \u226560 years (mean \u00b1 SD, 70.6 \u00b1 6.4 years; 41.6% female) from the Singapore Kidney Eye Study according to quintiles of leptin concentration (\u22642.64; 2.64\u20135.1; 5.2\u20138.6; 8.7\u201317.96; \u226518 ng\/mL). Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Age, gender, body mass index, mean arterial pressure, smoking, alcohol, education, memory complaint, anxiodepressive disorders, circulating concentrations of 25-hydroxyvitamin D, glycosylated hemoglobin, low-density lipoprotein cholesterol, and estimated glomerular filtration rate were used as potential confounders. Participants within the lowest (Q1) and highest (Q5) leptin quintiles exhibited lower (i.e., worse) mean total AMT scores compared to those within the intermediate quintiles (Q2, Q3, and Q4). Compared to Q3 as the reference, Q1 and Q5 were associated with decreased total AMT score (respectively, \u03b2 = \u22120.53 p = 0.018; \u03b2 = \u22120.60 p = 0.036). Compared to Q3, Q5 was also associated with decreased subscores on anterograde (\u03b2 = \u22120.19 p = 0.020) and retrograde episodic memories (\u03b2 = \u22120.18 p = 0.039). We found a non-linear U-shaped relationship between circulating leptin and cognition, with both lower and higher concentrations of leptin being associated with more severe cognitive impairment in community-dwelling older Asians.<\/jats:p>","DOI":"10.3390\/nu11030660","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T12:12:25Z","timestamp":1552997545000},"page":"660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["U-Shaped Relationship between Serum Leptin Concentration and Cognitive Performance in Older Asian Adults"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-8109","authenticated-orcid":false,"given":"Cedric","family":"Annweiler","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine, Angers University Hospital, University Memory Clinic of Angers, UPRES EA 4638, University of Angers, 49100 Angers, France"},{"name":"Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume T.","family":"Duval","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Angers University Hospital, University Memory Clinic of Angers, UPRES EA 4638, University of Angers, 49100 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Yu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, #06-13, SNEC Bldg, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Yin","family":"Wong","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, #06-13, SNEC Bldg, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ecosse L.","family":"Lamoureux","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, #06-13, SNEC Bldg, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Milea","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, #06-13, SNEC Bldg, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"Department of Ophthalmology, Angers University Hospital, 49100 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charumathi","family":"Sabanayagam","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, #06-13, SNEC Bldg, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/372425a0","article-title":"Positional cloning of the mouse obese gene and its human homologue","volume":"372","author":"Zhang","year":"1994","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/nm1195-1155","article-title":"Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects","volume":"1","author":"Maffei","year":"1995","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"731","DOI":"10.3233\/JAD-2009-1021","article-title":"Leptin: A novel therapeutic strategy for Alzheimer\u2019s disease","volume":"16","author":"Tezapsidis","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1530\/JME-12-0151","article-title":"Neuroprotective and anti-ageing role of leptin","volume":"49","author":"Folch","year":"2012","journal-title":"J. Mol. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cmet.2013.05.010","article-title":"Leptin at the intersection of neuroendocrinology and metabolism: Current evidence and therapeutic perspectives","volume":"18","author":"Dalamaga","year":"2013","journal-title":"Cell Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.yhbeh.2015.06.013","article-title":"Leptin attenuates the detrimental effects of \u03b2-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats","volume":"73","author":"Tong","year":"2015","journal-title":"Horm. Behav."},{"key":"ref_7","first-page":"321","article-title":"The Role of Leptin in Cognitive Development During Aging","volume":"46","author":"Zhang","year":"2015","journal-title":"Sheng Li Ke Xue Jin Zhan"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20130155","DOI":"10.1098\/rstb.2013.0155","article-title":"Leptin regulation of hippocampal synaptic function in health and disease","volume":"369","author":"Irving","year":"2013","journal-title":"Philos Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.biopsych.2008.10.006","article-title":"Relationship between plasma leptin level and brain structure in elderly: A voxel-based morphometric study","volume":"65","author":"Narita","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2174\/1567205010666131212114156","article-title":"Low plasma leptin in cognitively impaired ADNI subjects: Gender differences and diagnostic and therapeutic potential","volume":"11","author":"Johnston","year":"2014","journal-title":"Curr. Alzheimer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1159\/000447447","article-title":"Low Leptin Availability as a Risk Factor for Dementia in Chilean Older People","volume":"6","author":"Albala","year":"2016","journal-title":"Dement. Geriatr. Cogn. Dis. Extra"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/j.neurobiolaging.2011.05.008","article-title":"Serum leptin, thyroxine and thyroid-stimulating hormone levels interact to affect cognitive function among US adults: Evidence from a large representative survey","volume":"33","author":"Beydoun","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/WNR.0b013e32835c5254","article-title":"Alzheimer\u2019s Disease Neuroimaging Initiative. Fat-mass-related hormone, plasma leptin, predicts brain volumes in the elderly","volume":"24","author":"Rajagopalan","year":"2013","journal-title":"Neuroreport"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/jnc.12380","article-title":"Dysregulation of leptin signaling in Alzheimer disease: Evidence for neuronal leptin resistance","volume":"128","author":"Bonda","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3233\/JAD-141503","article-title":"Serum leptin is not altered nor related to cognitive decline in Alzheimer\u2019s disease","volume":"44","author":"Teunissen","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s12603-012-0058-4","article-title":"Ghrelin and leptin secretion in patients with moderate Alzheimer\u2019s disease","volume":"16","author":"Theodoropoulou","year":"2012","journal-title":"J. Nutr. Health Aging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3233\/JAD-2012-111385","article-title":"Lipids and adipokines as risk factors for Alzheimer\u2019s disease","volume":"29","author":"Warren","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1167\/iovs.14-15933","article-title":"Serum leptin and age-related macular degeneration","volume":"56","author":"Seshasai","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/09286580600878844","article-title":"Rationale and methodology for a population-based study of eye diseases in Malay people: The Singapore Malay Eye Study (SiMES)","volume":"14","author":"Foong","year":"2007","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"325","DOI":"10.3109\/09286580903144738","article-title":"Methodology of the Singapore Indian Chinese Cohort (SICC) eye study: Quantifying ethnic variations in the epidemiology of eye diseases in Asians","volume":"16","author":"Lavanya","year":"2009","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/ageing\/1.4.233","article-title":"Evaluation of a mental test score for assessment of mental impairment in the elderly","volume":"1","author":"Hodkinson","year":"1972","journal-title":"Age Ageing"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1111\/j.1532-5415.2010.03129.x","article-title":"Reliability and validity of the abbreviated mental test (Hong Kong version) in residential care homes","volume":"58","author":"Lam","year":"2010","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0167-4943(05)80007-X","article-title":"Study on the validity of the Hodkinson Abbreviated Mental Test Score (AMTS) in detecting dementia of elderly subjects in appignano (Macerata province), Italy","volume":"15","author":"Bonaiuto","year":"1992","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rochon, J., Gondan, M., and Kieser, M. (2012). To test or not to test: Preliminary assessment of normality when comparing two independent samples. BMC Med. Res. Methodol., 12.","DOI":"10.1186\/1471-2288-12-81"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2174\/13816128113199990015","article-title":"Leptin in thrombosis and atherosclerosis","volume":"20","author":"Wang","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1038\/ijo.2014.37","article-title":"The potential role of leptin in the vascular remodeling associated with obesity","volume":"38","author":"Miana","year":"2014","journal-title":"Int. J. Obes."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1161\/01.CIR.0000036864.14101.1B","article-title":"Does leptin cause vascular disease?","volume":"106","author":"Cooke","year":"2002","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10484-015-9301-1","article-title":"Serum leptin and cortisol, related to acutely perceived academic examination stress and performance in female university students","volume":"40","author":"Haleem","year":"2015","journal-title":"Appl. Psychophysiol. Biofeedback"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s11011-014-9501-z","article-title":"Obesity as a risk factor for Alzheimer\u2019s disease: The role of adipocytokines","volume":"29","author":"Letra","year":"2014","journal-title":"Metab. Brain Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1096\/fj.04-2572com","article-title":"Obesity-related leptin regulates Alzheimer\u2019s Abeta","volume":"18","author":"Fewlass","year":"2004","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1523\/JNEUROSCI.21-24-j0001.2001","article-title":"Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity","volume":"21","author":"Shanley","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1074\/jbc.M703753200","article-title":"Leptin-mediated cell survival signaling in hippocampal neurons mediated by JAK STAT3 and mitochondrial stabilization","volume":"283","author":"Guo","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000452908","article-title":"Leptin, Neuroinflammation and Obesity","volume":"48","author":"Dragano","year":"2017","journal-title":"Front. Horm. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tana, C., Ticinesi, A., Prati, B., Nouvenne, A., and Meschi, T. (2018). Uric Acid and Cognitive Function in Older Individuals. Nutrients, 10.","DOI":"10.3390\/nu10080975"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.2147\/CIA.S139163","article-title":"Gut microbiota, cognitive frailty and dementia in older individuals: A systematic review","volume":"13","author":"Ticinesi","year":"2018","journal-title":"Clin. Intervent. Aging"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/3\/660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:38:57Z","timestamp":1760186337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/3\/660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,19]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["nu11030660"],"URL":"https:\/\/doi.org\/10.3390\/nu11030660","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,19]]}}}