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Journal Article

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School of Medical and Health Sciences


Dementia Collaborative Research Centres program (DCRC2) Cooperative Research Centre (CRC) for Mental Health, the Australian Alzheimer’s Research Foundation and Operational Infrastructure Support from the Government of Victoria National Health and Medical Research Council (NHMRC): Boosting Dementia Research Leadership Fellowship #RM34909 Swedish Research Council (#2017-00915 and #2018-02532) Swedish Alzheimer Foundation (#AF-742881 and #FO2017-0243) Swedish Government and the County Councils, the ALF-agreement (#ALFGBG-715986) European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236) European Research Council (#681712 and #101053962) Swedish State Support for Clinical Research (#ALFGBG-71320) Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862) Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C) Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228) European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE) European Union Joint Programme—Neurodegenerative Disease Research (JPND2021-00694) UK Dementia Research Institute at UCL (UKDRI-1003)


Dhiman, K., Villemagne, V. L., Fowler, C., Bourgeat, P., Li, Q. X., Collins, S., ... & Gupta, V. (2022). Cerebrospinal Fluid Neurofilament Light Predicts Risk of Dementia Onset in Cognitively Healthy Individuals and Rate of Cognitive Decline in Mild Cognitive Impairment: A Prospective Longitudinal Study. Biomedicines, 10(5), 1045.


Background: Biomarkers that are indicative of early biochemical aberrations are needed to predict the risk of dementia onset and progression in Alzheimer’s disease (AD). We assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) chain for screening preclinical AD, predicting dementia onset among cognitively healthy (CH) individuals, and the rate of cognitive decline amongst individuals with mild cognitive impairment (MCI). Methods: Neurofilament light levels were measured in CSF samples of participants (CH, n = 154 and MCI, n = 32) from the Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL). Cases of preclinical AD were identified using biomarker-guided classification (CH, amyloid-b [Ab]+, phosphorylated-tau [P-tau]+ and total-tau [T-tau]±; A+T+/N±). The prediction of dementia onset (questionable dementia) among CH participants was assessed as the risk of conversion from Clinical Dementia Rating [CDR = 0] to CDR ≥ 0.5 over 6 years. Mixed linear models were used to assess the utility of baseline CSF NfL levels for predicting the rate of cognitive decline among participants with MCI over 4.5 years. Results: Neurofilament light levels were significantly higher in preclinical AD participants (CH, A+T+/N±) as compared to A-T-N-(p < 0.001). Baseline levels of CSF NfL were higher in CH participants who converted to CDR ≥ 0.5 over 6 years (p = 0.045) and the risk of conversion to CDR ≥ 0.5 was predicted (hazard ratio [HR] 1.60, CI 1.03–2.48, p = 0.038). CH participants with CSF NfL > cut-off were at a higher risk of developing dementia (HR 4.77, CI 1.31–17.29, p = 0.018). Participants with MCI and with higher baseline levels of CSF NfL ( > median) had a higher rate of decline in cognition over 4.5 years. Conclusion: An assessment of CSF NfL levels can help to predict dementia onset among CH vulnerable individuals and cognitive decline among those with MCI.



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