{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:27:18Z","timestamp":1785292038070,"version":"3.55.0"},"reference-count":58,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,10]],"date-time":"2025-08-10T00:00:00Z","timestamp":1754784000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Identifying predictive biomarkers of cognitive decline is critical for timely intervention in early Alzheimer's disease and related dementia. Biomarkers such as cerebrospinal fluid (CSF) neurofilament light (NfL), and MRI-based hippocampal atrophy are potential indicators of neurodegeneration, but their long-term predictive value remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study examined 20-year longitudinal associations between CSF NfL, MRI-based hippocampal atrophy, and cognitive decline in cognitively normal older adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cohort of 279 cognitively normal adults aged \u226555 years was followed from 2003 to 2023 at the Knight ADRC. Participants underwent annual cognitive and neurological assessments, including Clinical Dementia Rating (CDR), CSF NfL quantification, and MRI-based hippocampal volumetry. Cognitive decline was defined as: (1) first progression (CDR\u2009\u2265\u20090.5) and (2) sustained progression (two consecutive CDRs\u2009\u2265\u20090.5). Analyses included Kaplan-Meier survival, Cox proportional hazards models, and linear mixed-effects (LME) models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Participants had a mean age of 66.5 years (SD\u2009=\u20096.08); 58.4% were female. Mean follow-up was 11.41 years (SD\u2009=\u20093.5). First progression occurred in 71 participants (25.4%), and sustained progression in 35 (13%). Higher CSF NfL levels were associated with faster time to first (95% CI:0.2\u20131; p\u2009&lt;\u20090.001) and sustained progression (95% CI:0.46\u20131; p\u2009=\u20090.008). Cox models showed increased risk of first progression (HR\u2009=\u20091.83; 95% CI: 1.11\u20133.01; p\u2009=\u20090.018) but not sustained (p\u2009=\u20090.093). LME models showed CSF NfL increase and hippocampal volume decline (p\u2009&lt;\u20090.001) in both outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CSF NfL is a strong predictor of cognitive decline and may serve as a screening biomarker for early dementia risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251365219","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T06:53:37Z","timestamp":1754895217000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["The relationships between cerebrospinal fluid neurofilament light chain and hippocampal atrophy with cognitive decline"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9022-2317","authenticated-orcid":false,"given":"Ramkrishna K","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6514-0502","authenticated-orcid":false,"given":"Semere","family":"Bekena","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6106-1893","authenticated-orcid":false,"given":"Nikitha","family":"Damera","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-589X","authenticated-orcid":false,"given":"Yiqi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9187-0946","authenticated-orcid":false,"given":"Jean-Francois","family":"Trani","sequence":"additional","affiliation":[{"name":"School of Public Health, Washington University in St Louis, St Louis, MO, USA"},{"name":"National Conservatory of Arts and Crafts, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7966-3509","authenticated-orcid":false,"given":"Ganesh M","family":"Babulal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO, USA"},{"name":"Department of Psychology, University of Johannesburg, Johannesburg, South Africa"},{"name":"Institute of Public Health, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.08.047"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20527"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_3_3_6_2","article-title":"Understanding recent advances in non-amyloid\/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer\u2019s disease","volume":"10","author":"Van Eldik LJ","year":"2024","unstructured":"Van Eldik LJ, Siemers ER, Collins EC, et al. 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