Masebo, Lehane; Whitfield, Tim; Demnitz-King, Harriet; Heslegrave, Amanda; Poisnel, Geraldine; Lutz, Antoine; Frison, Eric; ... Marchant, Natalie L; + view all Masebo, Lehane; Whitfield, Tim; Demnitz-King, Harriet; Heslegrave, Amanda; Poisnel, Geraldine; Lutz, Antoine; Frison, Eric; Wirth, Miranka; Hye, Abdul; Jessen, Frank; Ashton, Nicholas J; Zetterberg, Henrik; Marchant, Natalie L; - view fewer (2025) Can non-pharmacological interventions change levels of neurofilament light in older adults at risk of dementia? A secondary analysis of the SCD-Well randomized clinical trial. The Journal of Prevention of Alzheimer's Disease , 12 (8) , Article 100299. 10.1016/j.tjpad.2025.100299.

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Abstract

Background: Older adults with subjective cognitive decline (SCD) and/or elevated neurofilament light (NfL), a neurodegeneration biomarker, are at increased risk of dementia. Non-pharmacological interventions offer a promising strategy for reducing dementia risk, yet none have utilized NfL as a marker of response in dementia prevention trials. / / Objective: To investigate the effects of two non-pharmacological interventions on NfL in older adults with SCD. / / Design: SCD-Well was an 8-week observer-blinded, randomized, clinical trial with 6-month follow-up, and was a part of the Horizon 2020 European Union-funded "Medit-Ageing" project. Data were analyzed from June 2022 to August 2024. / / Setting: Memory clinics at four sites in France, Germany, Spain, and UK. / / Participants: Participants were enrolled from March 2017 to January 2018 after fulfilling SCD research criteria and performing within the normal range on cognitive testing. Of the 147 participants enrolled, 140 were included in this secondary analysis (7 did not consent to venipuncture). / / Interventions: Participants were randomly allocated to the Caring Mindfulness-Based Approach for Seniors (CMBAS) intervention or a structurally matched Health Self-Management Program (HSMP). / / Measurements: Plasma NfL was measured at baseline (V1), post-intervention (V2), and 6-month follow-up (V3), using Single molecule array technology, and log-transformed for analyses. / / Results: 137 older adults with SCD provided NfL data (mean [SD] age: 72.7 [6.8] years; 62.0% female; CMBAS, n = 70; HSMP, n = 67). NfL data were available at V1 (n = 136), V2 (n = 119) and V3 (n = 115). The visit-by-arm interaction was not statistically significant, and no significant changes in NfL were observed within the CMBAS or HSMP arms from V1 to V2. However, within the HSMP arm, NfL levels reduced from V1 to V3 (-0.10, 95% confidence interval [-0.18 to -0.02]). Modified intention-to-treat analyses, which included 140 participants, supported these findings, and additionally recorded significant reductions in the HSMP arm from V1 to V2 (n = 140, -0.07 [-0.14 to -0.00]). / / Conclusions: In this study, NfL levels were reduced at 6-month follow-up after a health self-management program. Future interventions with longer duration, extended follow-up and clinical endpoints will help clarify whether NfL reductions are sustained over extended timeframes and translate to lower dementia incidence. / / Trial registration: ClinicalTrials.gov Identifier: (NCT03005652).

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