{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:55:49Z","timestamp":1768571749747,"version":"3.49.0"},"posted":{"date-parts":[[2025,5,21]]},"group-title":"Neurology","reference-count":36,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:bold>Introduction:<\/jats:bold>\n                  Dementia presents with significant heterogeneity across age groups, particularly in early-onset cognitive decline (EOCD), which poses diagnostic and management challenges. The Cognitive and Neuroimaging for Neurodegenerative Disorders (CogNID) study aims to characterise clinical, cognitive, neuroimaging, and biomarker features across a diverse cohort of individuals with cognitive impairment, with a focus on diagnostic complexity, biomarker utility, and mortality.\n                  <jats:bold>Methods:<\/jats:bold>\n                  Out of 680 study participants within this prospective cohort enrolled from the real-world clinics within the National Health Service, who consented to take part in the study, we analysed data from 429 individuals recruited between December 2018 and November 2024 from the Memory Clinics, including the young-onset dementia service and associated services. Participants underwent structured cognitive assessments, neuroimaging (MRI\/CT), and Cerebrospinal fluid (CSF) biomarker evaluation, where available. Diagnoses were made by multidisciplinary consensus. Group comparisons were conducted between early-onset (EOCD, &lt;65 years) and late-onset cognitive decline (LOCD, \u226565 years).\n                  <jats:bold>Results:<\/jats:bold>\n                  Of the 429 participants, 349 (81.4%) had EOCD and 80 (18.6%) had LOCD. The mean age was 60.05 years, with no significant difference in sex or ethnicity across groups. Depression and anxiety were common (29.6%), as were cardiovascular risk factors. Lumbar punctures were more frequently performed in EOCD (p = 0.03), with 36.4% of tested participants demonstrating biomarker profiles consistent with Alzheimer\u2019s disease (A+T+). Functional cognitive disorder (FCD) was more common in EOCD (22.3% vs. 5.0%, p &lt; 0.001). Subgroup analysis revealed significantly lower ACE-III scores and higher pathological CSF findings in Alzheimer\u2019s disease versus FCD. Mortality was higher in the LOCD group (11.3% vs. 4.6%, p = 0.03).\n                  <jats:bold>Conclusion:<\/jats:bold>\n                  The CogNID study highlights the clinical and diagnostic heterogeneity of individuals with cognitive impairment, particularly in younger adults. Incorporating neuroimaging and CSF biomarkers into routine clinical pathways enhances diagnostic precision and reveals distinct phenotypic profiles between EOCD and LOCD. These findings underscore the need for harmonised diagnostic protocols, broader biomarker accessibility, and inclusive recruitment strategies in dementia research and clinical services.\n                <\/jats:p>","DOI":"10.1101\/2025.05.19.25327923","type":"posted-content","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:40:17Z","timestamp":1747874417000},"source":"Crossref","is-referenced-by-count":0,"title":["Cognitive and Neuroimaging for Neurodegenerative Disorders: A Cohort Study Design with Initial Findings"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0133-9842","authenticated-orcid":false,"given":"Akram A.","family":"Hosseini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5333-370X","authenticated-orcid":false,"given":"Beili","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail Rebecca","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Permesh","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kehinde","family":"Junaid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Gran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Sellars","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Sargisson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JeYoung","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeta","family":"Mukaetova-Ladinska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025052407051108000_2025.05.19.25327923v1.1","doi-asserted-by":"crossref","first-page":"e088815","DOI":"10.1002\/alz.088815","article-title":"Correlation Between Cognitive Impairment in Early-Stage Amyloid-Positive Alzheimer\u2019s Disease and CA1 Hippocampal Subfield Volume Loss Using 7T MRI","volume":"20","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2025052407051108000_2025.05.19.25327923v1.2","unstructured":"Alzheimer\u2019s Society (2023) Alzheimer\u2019s Society says 19,000 people in England could be living with undiagnosed young-onset dementia. Alzheimer\u2019s Society. [online] Available at: https:\/\/www.alzheimers.org.uk\/news\/2023-10-20\/19000-people-england-could-be-living-undiagnosed-young-onset-dementia."},{"key":"2025052407051108000_2025.05.19.25327923v1.3","doi-asserted-by":"publisher","DOI":"10.1097\/wad.0000000000000279"},{"key":"2025052407051108000_2025.05.19.25327923v1.4","doi-asserted-by":"crossref","unstructured":"Bisschop, J.M. , de Jonge, H.J. , Brunsveld-Reinders, A.H. , van de Mheen, D.H. , Mathijssen, J.J. and Rozema, A.D. , 2025. Screening instruments to detect problematic alcohol use among adults in hospitals and their diagnostic test accuracy: A systematic review. Drug and Alcohol Review.","DOI":"10.1111\/dar.13987"},{"key":"2025052407051108000_2025.05.19.25327923v1.5","doi-asserted-by":"crossref","unstructured":"Bruno, D. and Schurmann Vignaga, S ., 2019. Addenbrooke\u2019s cognitive examination III in the diagnosis of dementia: a critical review. Neuropsychiatric disease and treatment, pp.441\u2013447.","DOI":"10.2147\/NDT.S151253"},{"issue":"6","key":"2025052407051108000_2025.05.19.25327923v1.6","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1192\/bjb.2021.104","article-title":"Differences in care between younger and older patients in the 2019 English national memory service audit","volume":"46","year":"2022","journal-title":"BJPsych Bulletin"},{"key":"2025052407051108000_2025.05.19.25327923v1.7","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.12.2308"},{"key":"2025052407051108000_2025.05.19.25327923v1.8","unstructured":"Dementia UK. (2025). Young onset dementia. [online] Available at: https:\/\/www.dementiauk.org\/information-and-support\/young-onset-dementia\/?gad_source=1&gclid=EAIaIQobChMI-uuojJ3wiQMVHaRQBh39pi6DEAAYASAAEgIjNfD_BwE"},{"key":"2025052407051108000_2025.05.19.25327923v1.9","doi-asserted-by":"crossref","first-page":"e076814","DOI":"10.1002\/alz.076814","article-title":"The cerebrospinal fluid A-T+ Alzheimer disease biomarker profile: prevalence and clinical relevance","volume":"19","year":"2023","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2025052407051108000_2025.05.19.25327923v1.10","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s40615-016-0332-y","article-title":"Barriers and strategies for recruitment of racial and ethnic minorities: perspectives from neurological clinical research coordinators","volume":"4","year":"2017","journal-title":"Journal of racial and ethnic health disparities"},{"key":"2025052407051108000_2025.05.19.25327923v1.11","doi-asserted-by":"crossref","first-page":"120607","DOI":"10.1016\/j.neuroimage.2024.120607","article-title":"Memory impairment in Amyloid\u03b2-status Alzheimer\u2019s disease is associated with a reduction in CA1 and dentate gyrus volume: In vivo MRI at 7T","volume":"292","year":"2024","journal-title":"Neuroimage"},{"issue":"1","key":"2025052407051108000_2025.05.19.25327923v1.12","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41398-025-03275-w","article-title":"Global burden of young-onset dementia, from 1990 to 2021: an age-period-cohort analysis from the global burden of disease study 2021","volume":"15","year":"2025","journal-title":"Translational Psychiatry"},{"issue":"9","key":"2025052407051108000_2025.05.19.25327923v1.13","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1001\/jamaneurol.2021.2161","article-title":"Global prevalence of young-onset dementia: a systematic review and meta-analysis","volume":"78","year":"2021","journal-title":"JAMA neurology"},{"issue":"2","key":"2025052407051108000_2025.05.19.25327923v1.14","doi-asserted-by":"crossref","first-page":"771","DOI":"10.3233\/JAD-215650","article-title":"Clinical Utility of Cerebrospinal Fluid A\u03b242 and Tau Measures in Diagnosing Mild Cognitive Impairment in Early Onset Dementia","volume":"87","year":"2022","journal-title":"Journal of Alzheimer\u2019s Disease"},{"key":"2025052407051108000_2025.05.19.25327923v1.15","doi-asserted-by":"publisher","DOI":"10.1159\/000351671"},{"key":"2025052407051108000_2025.05.19.25327923v1.16","unstructured":"Humphreys, G. , Bickerton, W.-L. , Samson, D. and Riddoch, J . (2012). BCoS Cognitive Screen. Psychology Press."},{"key":"2025052407051108000_2025.05.19.25327923v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy059"},{"issue":"8","key":"2025052407051108000_2025.05.19.25327923v1.18","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup","volume":"20","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2025052407051108000_2025.05.19.25327923v1.19","doi-asserted-by":"crossref","unstructured":"Khalatbari-Soltani, S. , Si, Y. , Dominguez, M. , Scott, T. and Blyth, F.M ., 2024. Worldwide cohort studies to support healthy ageing research: data availabilities and gaps. Ageing Research Reviews, p.102277.","DOI":"10.1016\/j.arr.2024.102277"},{"key":"2025052407051108000_2025.05.19.25327923v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)30367-6"},{"key":"2025052407051108000_2025.05.19.25327923v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00064-X"},{"key":"2025052407051108000_2025.05.19.25327923v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrl.2014.05.004"},{"issue":"2","key":"2025052407051108000_2025.05.19.25327923v1.23","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S2215-0366(19)30405-5","article-title":"Functional cognitive disorders: a systematic review","volume":"7","year":"2020","journal-title":"The Lancet Psychiatry"},{"key":"2025052407051108000_2025.05.19.25327923v1.24","unstructured":"National Institute for Healthand Care Excellence (NICE). (2018). Dementia: Assessment, management and support for people living with dementia and their carers. NICE Guideline 97, Methods, evidence and recommendations."},{"key":"2025052407051108000_2025.05.19.25327923v1.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"issue":"3","key":"2025052407051108000_2025.05.19.25327923v1.26","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.1192\/bjo.2019.36","article-title":"Young-onset dementia: scoping review of key pointers to diagnostic accuracy","volume":"5","year":"2019","journal-title":"BJPsych Open"},{"issue":"1","key":"2025052407051108000_2025.05.19.25327923v1.27","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1177\/1471301215626889","article-title":"How people come to recognise a problem and seek medical help for a person showing early signs of dementia: A systematic review and meta-ethnography","volume":"17","year":"2018","journal-title":"Dementia"},{"key":"2025052407051108000_2025.05.19.25327923v1.28","unstructured":"Rethink Mental Illness (2023). What is schizophrenia? [online] Available at: https:\/\/www.rethink.org\/advice-and-information\/about-mental-illness\/mental-health-conditions\/schizophrenia-the-key-facts\/."},{"key":"2025052407051108000_2025.05.19.25327923v1.29","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa438"},{"key":"2025052407051108000_2025.05.19.25327923v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00599-y"},{"key":"2025052407051108000_2025.05.19.25327923v1.31","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00702-018-01967-w","article-title":"Comparison of clinical and neuropathological diagnoses of neurodegenerative diseases in two centres from the Brains for Dementia Research (BDR) cohort","volume":"126","year":"2019","journal-title":"Journal of neural transmission"},{"issue":"1","key":"2025052407051108000_2025.05.19.25327923v1.32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2217\/nmt-2017-0029","article-title":"Understanding important issues in young-onset dementia care: The perspective of healthcare professionals","volume":"8","year":"2018","journal-title":"Neurodegenerative Disease Management"},{"issue":"1","key":"2025052407051108000_2025.05.19.25327923v1.33","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1186\/s12913-024-10947-8","article-title":"Identifying barriers to outpatient appointment attendance in patient groups at risk of inequity: a mixed methods study in a London NHS trust","volume":"24","year":"2024","journal-title":"BMC Health Services Research"},{"key":"2025052407051108000_2025.05.19.25327923v1.34","doi-asserted-by":"publisher","DOI":"10.1176\/appi.neuropsych.20100266"},{"key":"2025052407051108000_2025.05.19.25327923v1.35","doi-asserted-by":"publisher","DOI":"10.1002\/gps.2439"},{"key":"2025052407051108000_2025.05.19.25327923v1.36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1983.tb09716.x"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.05.19.25327923","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:36:31Z","timestamp":1768509391000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.05.19.25327923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":36,"URL":"https:\/\/doi.org\/10.1101\/2025.05.19.25327923","relation":{},"subject":[],"published":{"date-parts":[[2025,5,21]]},"subtype":"preprint"}}