Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition.

Osborn KE1, Khan OA1,2, Kresge HA1, Bown CW1, Liu D1,2, Moore EE1, Gifford KA1, Acosta LMY1, Bell SP1,3, Hohman TJ1,4, Blennow K5,6, Zetterberg H5,6,7,8, Jefferson AL1.

Author information

1: Vanderbilt Memory and Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
2: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
3: Divisions of Cardiovascular and Geriatric Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
4: Vanderbilt Genetics Institute, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
5: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
6: Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
7: Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
8: UK Dementia Research Institute at UCL, London, UK.

Abstract

INTRODUCTION:

Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage.

METHODS:

Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile.

RESULTS:

Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models.

DISCUSSION:

Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI.