7 FDA Approved CSF Biomarkers Demonstrate Strong Predictive Value for Identification of Alzheimer Disease Based on PET Scan in Patients with Standalone Alzheimer Cognitive Screening Tests.
Notice bibliographique
Résumé
Abstract Background Alzheimer’s disease, a progressive neurological disease, affects an estimated 6.7 million Americans aged 65 and older. Although positron emission tomography (PET) scan is the emerging gold standard for diagnosis of Alzheimer’s disease, Elecsys amyloid beta (Aβ42), total tau (t-Tau) and phosphorylated tau (p-Tau at position 181) in cerebral spinal fluid (CSF) have recently been approved by the FDA as surrogate biomarkers for Alzheimer’s disease. We implemented these Elecsys CSF assays in our laboratory using Cobas e801 analyzer and established a cut-off of > 0.024 for pTau181/Ab 42 ratio for indication of Alzheimer disease. We studied correlation between pTau181/Ab 42 ratio and actual diagnosis of Alzheimer’s disease based on PET scan in 143 patients. Materials and Methods All Elecsys assays were obtained from Roche and CSF specimens were collected using specialized Sarstedt tube supplied by Roche. Imaging studies were performed using fluorodeoxyglucose PET scans. Screening for cognitive function (SCF) in these patients was performed using either MOCA (Montreal Cognitive Assessment), SLUMS (Saint Louis University Mental Status Examination), STMS (The Short Test of Mental Status) or MMSE (Mini-Mental State Exam). Results There was no statistically significant difference in age of patients with the CSF biomarker ratio above the cut off limit of 0.024 (80 patients, mean age 71.3 years, SD: 7.9) and ratio below the cut-off (63 patients, mean age 66.3 years, SD :10.0) using Levene’s test. However, older patients were more likely to show an elevated pTau181/Ab 42 ratio. We observed no racial bias (Caucasian, African American, Hispanic and others) in elevated CSF biomarker results or positive PET scans using Chi-Square test. Chi-square analysis also showed a statistically significant association between positive CSF tests and PET scans (p < 0.01). The mean pTau181/Ab42 ratio was 0.055 (SD: 0.05, range: 0.025-0.12) in patients resulted positive for the CSF biomarkers, but the ratio was 0.0138 (SD: 0.0046, range: 0.007-0.024) in patients who tested negative (differences were also statistically significant by t-test). The sensitivity of pTau181/Ab42 was 76.2%, specificity was 84.2% and positive predictive value was 84.2% when compared to PET scan findings. We observed poor correlation between standalone SCF and PET scan result using Chi-Square analysis. For example, MOCA showed a sensitivity of 50.0%, specificity of 66.7% and positive predictive value of only 33.3%. However, binary logistic regression demonstrated a combination of abnormal SCF, and a positive CSF screen significantly predicted a positive imaging result (N = 40, p<.001). Conclusions CSF pTau181/Ab42 ratio is a diagnostic marker for Alzheimer disease correlated well with PET scan compared to various standalone cognitive screening assessment. A negative CSF biomarker test result may help rule out Alzheimer disease. Further, a combination approach inclusive of SCF and CSF biomarkers was significant for positive PET imaging.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».