Utility of Plasma Neurofilament Light in the 1Florida Alzheimer’s Disease Research Center (ADRC)

Author:

Barker Warren1,Quinonez Carlos1,Greig Maria T.1,Behar Raquel1,Chirinos Cesar1,Rodriguez Rosemarie A.1,Rosselli Monica2,Rodriguez Miriam J.3,Cid Rosie Curiel4,Rundek Tatjana5,McFarland Karen6,Hanson Kevin6,Smith Glenn6,DeKosky Steven6,Vaillancourt David6,Adjouadi Malek7,Marsiske Michael6,Ertekin-Taner Nilufer89,Golde Todd6,Loewenstein David A.4,Duara Ranjan1

Affiliation:

1. Wien Center for Alzheimer’s Disease and Memory Disorder, Mount Sinai Medical Center, Miami Beach, FL, USA

2. Florida Atlantic University, Department of Psychology, Charles E. Schmidt College of Science, Davie, FL, USA

3. Albizu University, Miami, FL, USA

4. Department of Psychiatry and Behavioral Sciences and Neurology, Miller School of Medicine, University of Miami, FL, USA

5. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA

6. Florida ADRC, University of Florida, Gainesville, FL, USA

7. College of Engineering and Computing, Florida International University, Miami, Florida, USA

8. Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL, USA

9. Mayo Clinic Florida, Department of Neurology, Jacksonville, FL, USA

Abstract

Background: Plasma NfL (pNfL) levels are elevated in many neurological disorders. However, the utility of pNfL in a clinical setting has not been established. Objective: In a cohort of diverse older participants, we examined: 1) the association of pNfL to age, sex, Hispanic ethnicity, diagnosis, and structural and amyloid imaging biomarkers; and 2) its association to baseline and longitudinal cognitive and functional performance. Methods: 309 subjects were classified at baseline as cognitively normal (CN) or with cognitive impairment. Most subjects had structural MRI and amyloid PET scans. The most frequent etiological diagnosis was Alzheimer’s disease (AD), but other neurological and neuropsychiatric disorders were also represented. We assessed the relationship of pNfL to cognitive and functional status, primary etiology, imaging biomarkers, and to cognitive and functional decline. Results: pNfL increased with age, degree of hippocampal atrophy, and amyloid load, and was higher in females among CN subjects, but was not associated with Hispanic ethnicity. Compared to CN subjects, pNfL was elevated among those with AD or FTLD, but not those with neuropsychiatric or other disorders. Hippocampal atrophy, amyloid positivity and higher pNfL levels each added unique variance in predicting greater functional impairment on the CDR-SB at baseline. Higher baseline pNfL levels also predicted greater cognitive and functional decline after accounting for hippocampal atrophy and memory scores at baseline. Conclusion: pNfL may have a complementary and supportive role to brain imaging and cognitive testing in a memory disorder evaluation, although its diagnostic sensitivity and specificity as a stand-alone measure is modest. In the absence of expensive neuroimaging tests, pNfL could be used for differentiating neurodegenerative disease from neuropsychiatric disorders.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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