Clinical evaluation of SPARE‐TauAD, an AV‐1451‐derived tau index. (1st February 2022)

• Record Type: Journal Article
• Authors: Toledo, Jon B.; Liu, Hangfan; Rashid, Tanweer; Habes, Mohamad
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.055440
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The deposition of abnormal proteins defines neurodegenerative diseases. Among these proteins, tau deposits define frontotemporal lobar degeneration (FTLD) tau, and together with Aβ, it defines the more prevalent Alzheimer's disease (AD). PET scans with ligands binding AD tau neurofibrillary tangles (NFT) topographically quantify the amount of pathology. However, for clinical purposes, this information needs to be summarized into easily applicable and meaningful indices. Here we develop a machine learning‐derived tau PET index, the Spatial Pattern of Abnormality for Recognition of Tau in AD (SPARE‐TauAD). Method: 603 subjects were included in the study. Their clinical diagnoses were: 366 cognitively normal (CN), 177 mild cognitive impairment (MCI), and 60 dementia subjects. These subjects were classified as Aβ positive and negative based on CSF Aβ1‐42 levels or florbetapir PET summary composite. SPARE‐TauAD was derived using a support vector machine classifier comparing AV‐1451 PET scans in 141 Aβ negative CN subjects against 108 Aβ positive MCI and dementia subjects. We then evaluated its association with CSF t‐tau, global cognition (measured using ADAS‐Cog 13), clinical diagnosis, and clinical progression. Result: SPARE‐TauAD and CSF t‐tau showed a moderate correlation (rho=0.51, p<0.0001). SPARE‐TauAD explained a larger variance of ADAS‐Cog13 scores (R2=0.60) compared to CSF t‐tau (R2=0.21) and the florbetapir PET summary composite (R2=0.23). Using 5‐fold cross‐validation in an independent sample of Aβ negative CN subjects (n=77) against Aβ positive MCI and dementia subjects (n=35 for CSF), SPARE‐TauAD showed higher balanced accuracy (79.6%) compared to CSF t‐tau (61.6%). SPARE‐TauAD was also associated with faster progression from CN to MCI/dementia (H.R.=6.83, p‐value<0.0001) and MCI to dementia (H.R.=3.43, p‐value<0.0001). Whereas CSF t‐tau was no associated with clinical progression. Conclusion: SPARE‐TauAD showed, as expected, a moderate association with CSF t‐tau. However, it offered better cross‐sectional classification accuracy and correlation with cognitive scores. It also outperformed CSF t‐tau to predict longitudinal progression in this small with limited longitudinal follow‐up. One limitation is that the SPARE‐TauAD index has been developed in an AD MCI and dementia cohort. The used tau ligand, AV‐1451, has a greater affinity for NFT present in AD than tau pathology present in FTLD‐tau.