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
Kunal Dhiman,
Victor L. Villemagne,
Christopher Fowler,
Pierrick Bourgeat,
Qiao-Xin Li,
Steven Collins,
Ashley I. Bush,
Christopher C. Rowe,
Colin L. Masters,
David Ames,
Kaj Blennow,
Henrik Zetterberg,
Ralph N. Martins,
Veer Gupta
Affiliations
Kunal Dhiman
IMPACT—The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, 75 Pigdons Rd, Geelong, VIC 3216, Australia
Victor L. Villemagne
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
Christopher Fowler
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3010, Australia
Pierrick Bourgeat
Australian e-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, QLD 4029, Australia
Qiao-Xin Li
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3010, Australia
Steven Collins
Department of Medicine, The University of Melbourne, Melbourne, VIC 3010, Australia
Ashley I. Bush
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3010, Australia
Christopher C. Rowe
Department of Molecular Imaging & Therapy and Centre for PET, Austin Health, Melbourne, VIC 3084, Australia
Colin L. Masters
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3010, Australia
David Ames
National Ageing Research Institute, Melbourne, VIC 3052, Australia
Kaj Blennow
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 43180 Mölndal, Sweden
Henrik Zetterberg
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 43180 Mölndal, Sweden
Ralph N. Martins
School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia
Veer Gupta
IMPACT—The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, 75 Pigdons Rd, Geelong, VIC 3216, Australia
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-β [Aβ]+, 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 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.
