Abstract
Assessment of amyloid deposits is a critical step for the identification of Alzheimer disease (AD) signature in asymptomatic elders. Whether the different amyloid processing methods impacts on the quality of clinico-radiological correlations is still unclear. We directly compared in 155 elderly controls with extensive neuropsychological testing at baseline and 4.5 years follow-up three approaches: (i) operator-dependent standard visual reading, (ii) operator-independent automatic SUVR with four different reference regions, and (iii) novel operator and region of reference-independent automatic Aβ-index. The coefficient of variance was used to examine inter-individual variability for each processing method. Using visually-established amyloid positivity as the gold standard, the area under the receiver operating characteristic curve (ROC) was computed. Linear regression models were used to assess the association between changes in continuous cognitive score and amyloid uptake values. In SUVR analyses, the coefficient of variance varied from 1.718 to 1.762 according to the area of reference and was of − 3.045 for the Aβ-index method. Compared to the visual rating, Aβ-index method showed the largest area under the ROC curve [0.9568 (95% CI 0.9252, 0.98833)]. The best cut-off score was of − 0.3359 with sensitivity and specificity values of 0.97 and 0.83, respectively. Only the Aß-index was related to more severe decrement of cognitive performances [regression coefficient: 9.103 (95% CI 1.148, 17.058)]. The Aβ-index is considered as preferred option in asymptomatic elders, since it is operator-independent, avoids the selection of reference area, is closer to established visual scoring and correlates with the evolution of cognitive performances.
Highlights
Assessment of amyloid deposits is a critical step for the identification of Alzheimer disease (AD) signature in asymptomatic elders
According to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) documentation, this visual analysis is based on the notion that amyloid position emission tomography (PET) tracers physiologically bind only to the white matter (WM) yet not the grey matter (GM)
The present data reveal that the type of amyloid processing has a significant impact on inter-individual variability and clinico-radiological associations in asymptomatic elderly individuals
Summary
Assessment of amyloid deposits is a critical step for the identification of Alzheimer disease (AD) signature in asymptomatic elders. If there is abnormal uptake in the GM in at least one anatomic region (parietal cortex, temporal cortex, frontal cortex, anterior cingulate cortex, posterior cingulate cortex/precuneus and striatum) the scan is considered abnormal While this visual analysis does not need any specific post-processing tools, it requires time from an experienced human reader, is operator-dependent, and be prone to intra- and inter-rater discrepancies. Another operator-independent analysis method is automatic spatial normalization of the individual brain into an atlas standard space (oftentimes the Montreal neurological institute MNI space) followed by the automatic assessment of standardized uptake value (SUV) ratio (SUVR) between a set of predefined atlas regions versus a reference region. We had the opportunity to explore the performance of this method compared to visual inspection and quantitative SUVR data with various areas of reference in a large community-based cohort of cognitively preserved elders with full neuropsychological documentation at baseline and 4.5 years cognitive follow-up
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