Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".