Visual atrophy rating scales and amyloid PET status in an Alzheimer's disease clinical cohort

Abstract

Objectives: Visual rating scales (VRS) are the quantification method closest to the approach used in routine clinical practice to assess brain atrophy. Previous studies have suggested that the medial temporal atrophy (MTA) rating scale is a reliable diagnostic marker for AD, equivalent to volumetric quantification, while others propose a higher diagnostic utility for the Posterior Atrophy (PA) scale in early-onset AD.

Methods: Here, we reviewed 14 studies that assessed the diagnostic accuracy of PA and MTA, we explored the issue of cut-off heterogeneity, and assessed 9 rating scales in a group of patients with biomarker-confirmed diagnosis. A neuroradiologist blinded to all clinical information rated the MR images of 39 amyloid-positive and 38 amyloid-negative patients using 9 validated VRS assessing multiple brain regions. Automated volumetric analyses were performed on a subset of patients (n = 48) and on a group of cognitively normal individuals (n = 28).

Results: No single VRS could differentiate amyloid-positive from amyloid-negative patients with other neurodegenerative conditions. 44% of amyloid-positive patients were deemed to have age-appropriate levels of MTA. In the amyloid-positive group, 18% had no abnormal MTA or PA scores. These findings were substantially affected by cut-off selection. Amyloid-positive and amyloid-negative patients had comparable hippocampal and parietal volumes, and MTA but not PA scores correlated with the respective volumetric measures.

Interpretation: Consensus guidelines are needed before VRS can be recommended for use in the diagnostic workup of AD. Our data are suggestive of high intragroup variability and non-superiority of volumetric quantification of atrophy over visual assessment.

Figure 1

Heatmaps showing individual‐level visual rating scores in the amyloid‐negative (A) and amyloid‐positive (B) groups. Crossed‐out cells indicate missing visual rating score for that patient due to unavailable MR sequences. Percentages indicate the proportion of abnormal scores in each scale, dichotomized as per Table S3.

Figure 2

Combination of MTA and PA status in the amyloid‐positive and amyloid‐negative groups.

Figure 3

Quantification of the left and right parietal (A) and hippocampal (B) volumes in the amyloid‐positive, amyloid‐negative, and cognitively normal groups. ANCOVAs with “Group” as independent variable, and age, sex, and eTIV as covariates, revealed significant group differences for the hippocampal but not the parietal volumes. *p < 0.05; **p < 0.01; ns, nonsignificant.

Figure 4

Distribution of visual rating scores for each rating scale. Plotted scores are the result of the average between the left and right hemisphere scores.