title: CSF neurofilament light levels predict hippocampal atrophy in cognitively healthy older adults.
abstract: Cerebrospinal fluid (CSF) neurofilament light (NFL) is a marker of axonal degeneration. We tested whether CSF NFL levels predict hippocampal atrophy rate in cognitively healthy older adults independently of the established CSF Alzheimer's disease (AD) biomarkers, β-amyloid 1-42, and phosphorylated tau (P-tau). We included 144 participants in a 2-year longitudinal study with baseline CSF measures and 2 magnetic resonance images. Eighty-eight participants had full data available. A subgroup of 36 participants with very low AD risk was also studied. NFL predicted hippocampal atrophy rate independently of age, β-amyloid 1-42, and P-tau. Including NFL, P-tau, and age in the same model, higher NFL and lower P-tau predicted higher hippocampal atrophy (R2= 0.20, NFL: β = -0.34; p = 0.003; P-tau: β = 0.27; p = 0.009). The results were upheld in the participants with very low AD risk. NFL predicted neurodegeneration in older adults with very low AD probability. We suggest that factors previously shown to be important for brain degeneration in mild cognitive impairment may also impact changes in normal aging, demonstrating that NFL is likely to indicate AD-independent, age-expected neurodegeneration.
authors: Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway. Electronic address: av.idland@gmail.com.
authors: Ane-Victoria
authors: AV
authors: Idland
authors: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
authors: Roser
authors: R
authors: Sala-Llonch
authors: Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway.
authors: Tom
authors: T
authors: Borza
authors: Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: Leiv Otto
authors: LO
authors: Watne
authors: Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
authors: Torgeir Bruun
authors: TB
authors: Wyller
authors: Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors: Anne
authors: A
authors: Brækhus
authors: Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors: Henrik
authors: H
authors: Zetterberg
authors: Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
authors: Kristine Beate
authors: KB
authors: Walhovd
authors: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
authors: Anders Martin
authors: AM
authors: Fjell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D001284:Atrophy; D001369:Axons / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000166:cytology* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000175:diagnosis / Q000473:pathology; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers
keywords: Cerebrospinal fluid; Hippocampal atrophy rate; Magnetic resonance imaging; Neurofilament light; Normal aging