P1‐025: Olfactory identification is associated with CSF tau/abeta42 ratios in cognitively normal adults at high risk of Alzheimer's disease
Bibliographic record
Abstract
Olfactory impairment may reflect severity and neuropathological hallmarks of Alzheimer's disease (AD) in pre-symptomatic individuals (Wilson, 2009). When controls, MCI and AD participants were combined, olfactory identification was correlated with in vivo PET measures of Aβ using Pittsburgh Compound B (PiB), but this association did not hold when the groups were analyzed separately (Bahar-Fuchs, 2010). Studying aging cognitively intact persons at risk for AD, we sought to investigate the association of olfactory identification and cerebrospinal fluid (CSF) ratios of total tau (t-tau) or P-tau to Aβ42, commonly used biomarkers of AD progression. We hypothesized that olfactory test results might usefully add to other markers of AD progression, e.g., in clinical trials. We studied 74 cognitively normal people with a parental history of AD aged >55 yrs. Subjects underwent lumbar puncture and took the University of Pennsylvania Smell Identification Test (UPSIT). We excluded people with incomplete test scores, history of brain injury, TIA, stroke, nasal polyps or other nasal operations, asthma, or complaint of nasal congestion on exam date. In collaboration with the European Joint Program in Neurodegeneration (JPND), we used ELISA (Innotest/Fujirebio previously Innogenetics) to analyze CSF t-tau, P-tau, and Aβ42 levels. In a robust fit regression analysis, decrease in olfactory identification was associated with t-tau /Aβ42 (F=17.7, r=0.197, p<0.0001; Fig 1a) and P-tau /Aβ42 (F=13.7, r=0.159, p=0.0004; Fig 1b). In cross-sectional investigation of high-risk aging cognitively normal persons, t-tau and P-tau/Aβ42 ratios were robustly associated with reduced olfactory identification. We suggest that olfactory identification, and possibly other deficits in higher-level sensory processing, may be a sign of neurodegeneration in normal aging, and especially in the early stages of AD pathology. Within-subject longitudinal study designs may be more instructive still. Thus, it will be important to learn whether olfactory identification and other sensory processing functions may serve as convenient and non-invasive metrics of evolving neurodegeneration. Scatterplot graphs of robust fit regression analysis for smell identification test scores (UPSIT) and CSF biomarker ratios (t-tau/Aβ42, p-tau/Aβ42). Scatterplot graphs show robust fit regression plots showing CBF association with olfactory identification: a) as olfactory identification worsen t-tau/Aβ42 increase b] as olfactory identification worsen p-tau/Aβ42 increase.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".