Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment

James P. Naude, Sascha Gill, Sophie Hu, Alexander McGirr, Nils D. Forkert, Oury Monchi, Peter K. Stys, Eric E. Smith, Zahinoor Ismail, for the Alzheimer's Disease Neuroimaging Initiative
2020 Journal of Alzheimer's Disease  
Assessing neuropsychiatric symptoms (NPS) in older adults is important for determining dementia risk. Mild behavioral impairment (MBI) is an at-risk state for cognitive decline and dementia, characterized by emergent NPS in later life. MBI has significantly higher dementia incidence than late life psychiatric conditions. However, its utility as a proxy for neurodegeneration has not been demonstrated. Plasma neurofilament light (NfL) is a validated biomarker of axonal damage, and has been shown
more » ... and has been shown to associate with hallmarks of neurodegeneration. The purpose of this investigation was to identify associations between NfL rate of change and the presence of MBI symptomatology. We evaluated the association of MBI with changes in NfL in a cohort (n = 584; MBI + n = 190, MBI- n = 394) of non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. MBI was determined by transforming neuropsychiatric questionnaire items using a published algorithm. Change in NfL was calculated over 2 years. Time*MBI status was the only significant interaction to predict change in NfL concentrations (F(1,574) = 4.59, p = 0.032), even after controlling for age, mild cognitive impairment, and demographics. Analyses reclassifying 64 participants with new onset MBI over 2 years similarly demonstrated greater increases in NfL (F(1,574) = 5.82, p = 0.016). These findings suggest MBI is a clinical proxy of early phase neurodegeneration with putative utility in identifying those at dementia risk. MBI can be used as a case ascertainment approach to capture those at high risk for cognitive decline and dementia, and is an important construct for clinicians dealing with cognitive and neuropsychiatric symptomatology in older adults.
doi:10.3233/jad-200011 pmid:32597801 fatcat:lqftsuvpdfcrtaimdqsatyjnq4