{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:49:24Z","timestamp":1792446564083,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":37,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201023\u2010IAHU\u20100011"],"award-info":[{"award-number":["ANR\u201023\u2010IAHU\u20100011"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006556","name":"Centre Hospitalier Universitaire de Toulouse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006556","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&D Transl Res & Clin Interv"],"published-print":{"date-parts":[[2025,4]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Although recent studies have suggested a positive association between plasma neurofilament light chain (NfL) and depressive symptoms, the moderating effect of cognitive performance on this relationship remains unclear. The aim of this study was to investigate the association between NfL and depressive symptoms in a population of community\u2010dwelling older adults and to determine whether cognitive status could modify this relationship.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n This is a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 512 individuals (60.2% women) with a median age of 76 years (interquartile range [IQR]: 7) and with available data for plasmatic NfL levels. Depressive symptoms and cognitive status were assessed using the 15\u2010item Geriatric Depression Scale (GDS\u201015) and the Clinical Dementia Rating (CDR) scale, respectively. Multivariable linear regression analyses were conducted to explore the cross\u2010sectional association between GDS\u201015 (dependent variable) and plasma NfL levels (pg\/mL). The interaction between CDR status (binary: 0 or 0.5) and NfL levels in relation to depressive symptoms was also examined, followed by exploratory simple\u2010slope analyses according to CDR status.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n No significant association was observed between GDS\u201015 scores and plasma NfL levels (\n B<\/jats:italic>\n \u00a0=\u00a00.002, standard error [SE]\u00a0=\u00a00.001,\n p<\/jats:italic>\n \u00a0=\u00a00.08) in the entire sample. Although the CDR\u2013NfL interaction was not significant (\n B<\/jats:italic>\n \u00a0=\u00a00.003, SE\u00a0=\u00a00.002,\n p<\/jats:italic>\n \u00a0=\u00a00.17), exploratory simple\u2010slope analyses revealed that elevated NfL levels were associated with GDS\u201015 scores (\n N<\/jats:italic>\n \u00a0=\u00a0233,\n B<\/jats:italic>\n \u00a0=\u00a00.004, SE\u00a0=\u00a00.002,\n p<\/jats:italic>\n \u00a0=\u00a00.03) among individuals with a CDR 0.5, but not among those with a CDR 0 (\n N<\/jats:italic>\n \u00a0=\u00a0186,\n p<\/jats:italic>\n \u00a0=\u00a00.81).\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n NfL levels were not significantly associated with GDS\u201015 in a population of community\u2010dwelling older adults without dementia. Although no significant CDR\u2013NfL interaction was detected, exploratory analyses suggest that plasma NfL might be associated with GDS\u201015 scores only among people with a CDR 0.5 (indicative of mild cognitive impairment). Further studies with larger sample sizes are needed to elucidate the potential biological differences in depressive symptoms across different cognitive statuses.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Plasma neurofilament light (NfL) levels might be associated with 15\u2010Geriatric Depression Scale (GDS\u201015) scores only among people with Clinical Dementia Rating (CDR) 0.5 (indicative of mild cognitive impairment [MCI]), but not among those with CDR 0 (normal cognition).<\/jats:p>\n <\/jats:list-item>\n \n Depressive symptoms arising in the context of cognitive impairment may represent a distinct clinical entity compared to those observed in individuals with normal cognitive functioning.<\/jats:p>\n <\/jats:list-item>\n \n Further research with larger sample sizes is needed to elucidate potential biological differences in depressive symptoms across varying cognitive statuses (unimpaired cognition, MCI, and dementia).<\/jats:p>\n <\/jats:list-item>\n 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Cit\u00e9 de la Sant\u00e9 Place Lange Toulouse France"},{"name":"CERPOP, Inserm 1295 Toulouse University INSERM, UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Angioni","sequence":"additional","affiliation":[{"name":"IHU HealthAge La Cit\u00e9 de la Sant\u00e9 Place Lange Toulouse France"},{"name":"CERPOP, Inserm 1295 Toulouse University INSERM, UPS Toulouse France"},{"name":"Alzheimer's Disease Research and Clinical Center Toulouse University Hospital Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Romana","sequence":"additional","affiliation":[{"name":"Institut du Vieillissement G\u00e9rontop\u00f4le de Toulouse Centre Hospitalo\u2010Universitaire de Toulouse Toulouse France"},{"name":"Centre Hospitalo\u2010Universitaire de la Guadeloupe Route de Chauvel Guadeloupe 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Toulouse Centre Hospitalo\u2010Universitaire de Toulouse Toulouse France"},{"name":"IHU HealthAge La Cit\u00e9 de la Sant\u00e9 Place Lange Toulouse France"},{"name":"CERPOP, Inserm 1295 Toulouse University INSERM, UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the MAPT\/DSA study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/6166775"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)30367\u20106"},{"issue":"4","key":"e_1_2_8_4_1","first-page":"274","article-title":"Hypertension as a risk factor for developing depressive symptoms among community\u2010dwelling elders","volume":"61","author":"Garc\u00eda\u2010Fabela L","year":"2009","journal-title":"Rev Investig 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