doi:10.1038/s41598-025-95411-1engZapater-Fajarí, MariolaCrespo-Sanmiguel, IsabelCedres, NiraRydberg Sterner, ThereseRydén, LinaSacuiu, SimonaWaern, MargdaZettergren, AnnaZetterberg, HenrikBlennow, KajKern, SilkeHidalgo, VanesaSalvador, AliciaWestman, EricSkoog, IngmarFerreira, DanielLoneliness and biomarkers of brain pathology in people with subjective cognitive declineART-2025-143710Loneliness is a neuropsychiatric symptom that has been associated with cognitive impairment and dementia. We aimed to investigate whether depressive symptomatology and biomarkers of Alzheimer’s disease (AD) and cerebrovascular disease (CVD) are associated with loneliness. Secondly, we aimed to investigate whether loneliness, depressive symptomatology, and biomarkers of AD and CVD are associated with subjective cognitive decline (SCD). We included 215 cognitively unimpaired participants (70 y/o) with cerebrospinal fluid biomarkers, magnetic resonance imaging, and questionnaires for loneliness, depressive symptomatology, and SCD. For aim 1, our findings showed that CVD and depressive symptomatology were the most relevant measures to discriminate people with loneliness. For aim 2, a random forest classification model showed that loneliness contributed to discriminate individuals with SCD, but logistic regression showed that its partial predictive effect was non-significant when depressive symptomatology and AD biomarkers were included in the models. We conclude that loneliness is associated with SCD, CVD, and depressive symptomatology. Given the complex interplay between loneliness, depressive symptomatology, and SCD, more research is needed to fully clarify the unique role of each neuropsychiatric symptom in relation to biomarkers of brain pathology.2025http://zaguan.unizar.es/record/15322610.1038/s41598-025-95411-1http://zaguan.unizar.es/record/153226oai:zaguan.unizar.es:153226info:eu-repo/grantAgreement/ES/DGA/S31-23Rinfo:eu-repo/grantAgreement/ES/MICIU/PID2020-119406GB-I00Scientific reports (Nature Publishing Group) 15, 1 (2025)byhttps://creativecommons.org/licenses/by/4.0/deed.esinfo:eu-repo/semantics/openAccess