Association of Neuropsychiatric Symptoms with Blood‐Based Biomarkers pTAU181, NFL, and GFAP in Alzheimer's Disease and Mild Cognitive Impairment
Bibliographic record
Abstract
BACKGROUND: Neuropsychiatric Symptoms (NPS) in Alzheimer's Disease (AD) can exacerbate symptom burden and impair quality of life in patients. It is imperative to gain a better understanding of factors that contribute to NPS manifestation. This study explores the association between NPS scores and blood-based biomarkers implicated in AD including Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NFL), Amyloid Beta 40 (AB40), Amyloid Beta 42 (AB42), and Phosphorylated Tau at Threonine 181 (pTAU181). METHODS: Individuals with a diagnosis of Alzheimer's Disease (AD) or Mild Cognitive Impairment (MCI) were included based on data from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) database. From 126 participants, 107 had completed the Neuropsychiatric Inventory Questionnaire (NPI-Q) and provided blood samples for measurement of GFAP, NFL, AB40, AB42, and pTAU181 plasma levels. To assess the association between NPS severity scores and blood-based biomarkers, a partial Spearman correlation was conducted; adjusting for age, sex, and education level. A False Discovery Rate (FDR) threshold of 0.05 was applied to all p-values to control for multiple comparisons. RESULTS: We found significant correlations between several NPS domains and blood-based biomarkers. Apathy scores had a significant positive correlation with pTAU181 (Rs = 0.27, p = 0.04) and NFL plasma levels (Rs =0.30, p = 0.02); Anxiety scores showed a significant positive correlation with GFAP (Rs = 0.28, p = 0.03) and NFL plasma levels (Rs = 0.33, p = 0.006); Euphoria scores were positively correlated with NFL plasma levels (Rs = 0.27, p = 0.05); Appetite, Motor function, and Total NPI severity scores had a significant positive correlation with GFAP plasma levels (Rs = 0.31, p = 0.01; Rs = 0.31, p = 0.01; Rs = 0.29, p = 0.03). No significant findings were observed for AB40 and 42 with any NPS domain. CONCLUSION: Our findings suggest that certain blood-based biomarkers-pTAU181, NFL, and GFAP- are associated with the development of NPS in Alzheimer's Disease. These biomarkers may help shed light on underlying mechanisms and monitor NPS severity. However, further research in larger cohorts and longitudinal studies is needed to confirm these findings and explore causal relationships.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".