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Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment
James P Naude1, Sascha Gill1,2, Sophie Hu1,3
1Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Background:
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 to associate with hallmarks of neurodegeneration.
Objective:
The purpose of this investigation was to identify associations between NfL rate of change and the presence of MBI symptomatology.
Methods:
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 Inventory Questionnaire items using a published algorithm. Change in NfL was calculated over 2 years.
Results:
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).
Conclusion:
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.
Insights
Mild behavioral impairment (MBI) in older adults is linked to increased neurofilament light (NfL) levels, a marker of axonal damage. This suggests MBI may indicate early neurodegeneration and help identify dementia risk.
Area of Science:
- Neuroscience
- Geriatrics
- Biomarker Research
Background:
- Assessing neuropsychiatric symptoms (NPS) in older adults is crucial for dementia risk assessment.
- Mild behavioral impairment (MBI) signifies an at-risk state for cognitive decline, characterized by emergent NPS.
- MBI shows higher dementia incidence than other late-life psychiatric conditions, but its link to neurodegeneration requires demonstration.
Purpose of the Study:
- To investigate the association between the rate of change in plasma neurofilament light (NfL) and the presence of MBI symptomatology.
- To explore NfL as a potential biomarker for neurodegeneration in individuals with MBI.
Main Methods:
- Utilized data from 584 non-demented participants in the Alzheimer's Disease Neuroimaging Initiative.
- Assessed MBI by transforming Neuropsychiatric Inventory Questionnaire items.
- Calculated the change in plasma NfL concentrations over a 2-year period.
Main Results:
- A significant interaction between time and MBI status predicted changes in NfL concentrations (p=0.032).
- Reanalysis of participants with new-onset MBI over 2 years showed significantly greater increases in NfL (p=0.016).
- These associations remained significant after controlling for age, mild cognitive impairment, and demographics.
Conclusions:
- Mild behavioral impairment (MBI) may serve as a clinical proxy for early-stage neurodegeneration.
- MBI can aid in identifying individuals at higher risk for cognitive decline and dementia.
- MBI is a valuable construct for clinicians managing cognitive and neuropsychiatric symptoms in older adults.
