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This study evaluates the diagnostic performance of plasma biomarkers (neurofilament light chain and phosphorylated tau181) and retinal biomarkers (retinal nerve fibre layer and ganglion cell-inner plexiform layer), individually and in combination, in differentiating moderate cognitive impairment and dementia from mild cognitive impairment and no cognitive impairment. A cross-sectional study was conducted involving 509 participants, aged 50 and older, recruited from a memory clinic. The participants were categorized as normal (n = 100), mild cognitive impairment (n = 144), moderate cognitive impairment (n = 90) or dementia (n = 175) based on detailed clinical assessments, neuropsychological testing and MRI scans. The thickness of the ganglion cell-inner plexiform layer (P &amp;lt; 0.001) and retinal nerve fibre layer (P = 0.030) decreased progressively from normal cognition to cognitive impairment and dementia. The thickest layers were observed in individuals with no cognitive impairment (mean \u00b1 standard deviation: ganglion cell-inner plexiform layer: 76 \u00b1 11\u2005\u00b5m, retinal nerve fibre layer: 92 \u00b1 10\u2005\u00b5m), while the thinnest layers were found in individuals with dementia (ganglion cell-inner plexiform layer: 72 \u00b1 14\u2005\u00b5m, retinal nerve fibre layer: 89 \u00b1 12\u2005\u00b5m). Plasma biomarker levels increased progressively from normal cognition to cognitive impairment and dementia (P &amp;lt; 0.001). Levels were lowest in individuals with no cognitive impairment [median (interquartile range): neurofilament light chain: 15 (9) pg\/mL, phosphorylated tau181: 1.85 (1.00) pg\/mL] and highest in those with dementia [neurofilament light chain: 34 (27) pg\/mL, phosphorylated tau181: 3.24 (2.81) pg\/mL]. After adjusting for retinal scan signal strength, neurofilament light chain showed a stronger negative association with retinal nerve fibre layer thickness [standardized beta estimate (\u03b2) = \u22120.184] and ganglion cell-inner plexiform layer thickness (\u03b2 = \u22120.139) compared to phosphorylated tau181, which exhibited weaker associations with ganglion cell-inner plexiform layer (\u03b2 = \u22120.091) and retinal nerve fibre layer (\u03b2 = \u22120.059). While retinal parameters provided modest discriminatory ability (AUC = 0.60), plasma biomarkers demonstrated superior diagnostic performance (AUC = 0.76). Notably, neurofilament light chain had a stronger association with retinal thinning than phosphorylated tau181 and offered superior diagnostic value for identifying moderate cognitive decline. These findings underscore the potential of plasma biomarkers, particularly neurofilament light chain, for the early detection of dementia.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae472","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T15:07:42Z","timestamp":1735312062000},"source":"Crossref","is-referenced-by-count":9,"title":["Diagnosis of cognitive impairment and dementia: blood plasma and optical coherence tomography"],"prefix":"10.1093","volume":"7","author":[{"given":"Vidishaa","family":"Jali","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Memory Aging and Cognition Centre, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Memory Aging and Cognition Centre, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]},{"name":"Department of Neurosurgery, Tsinghua University Yuquan Hospital , Beijing 100040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce Ruifen","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Memory Aging and Cognition Centre, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damon","family":"Wong","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, The Academia , Singapore 169856 ,","place":["Singapore"]},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, National University of Singapore , Singapore 169857 ,","place":["Singapore"]},{"name":"SERI-NTU Advanced Ocular Engineering (STANCE) , Nanyang Technological University, Singapore 639798 ,","place":["Singapore"]},{"name":"School of Chemical and Biological Engineering, Nanyang Technological University , Singapore 637371 ,","place":["Singapore"]},{"name":"Institute of Molecular and Clinical Ophthalmology , The University of Basel, Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyao","family":"Tan","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, The Academia , Singapore 169856 ,","place":["Singapore"]},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, National University of Singapore , Singapore 169857 ,","place":["Singapore"]},{"name":"SERI-NTU Advanced Ocular Engineering (STANCE) , Nanyang Technological University, Singapore 639798 ,","place":["Singapore"]},{"name":"School of Chemical and Biological Engineering, Nanyang Technological University , Singapore 637371 ,","place":["Singapore"]},{"name":"Institute of Molecular and Clinical Ophthalmology , The University of Basel, Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Garh\u00f6fer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University Vienna , Wien 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saima","family":"Hilal","sequence":"additional","affiliation":[{"name":"Saw Swee Hock School of Public Health, National University of Singapore , Singapore 117549 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell K P","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Memory Aging and Cognition Centre, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopold","family":"Schmetterer","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, The Academia , Singapore 169856 ,","place":["Singapore"]},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, National University of Singapore , Singapore 169857 ,","place":["Singapore"]},{"name":"SERI-NTU Advanced Ocular Engineering (STANCE) , Nanyang Technological University, Singapore 639798 ,","place":["Singapore"]},{"name":"School of Chemical and Biological Engineering, Nanyang Technological University , Singapore 637371 ,","place":["Singapore"]},{"name":"Institute of Molecular and Clinical Ophthalmology , The University of Basel, Basel 4031 ,","place":["Switzerland"]},{"name":"Fondation Ophtalmologique Adolphe De Rothschild , Paris 75019 ,","place":["France"]},{"name":"Center for Medical Physics and Biomedical Engineering, Medical University Vienna , Wien 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Li-Hsian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Memory Aging and Cognition Centre, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-5293","authenticated-orcid":false,"given":"Jacqueline","family":"Chua","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, The Academia , Singapore 169856 ,","place":["Singapore"]},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, National University of Singapore , Singapore 169857 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