Medial temporal atrophy in preclinical dementia: Visual and automated assessment during six year follow-up

Abstract

Medial temporal lobe (MTL) atrophy is an important morphological marker of many dementias and is closely related to cognitive decline. In this study we aimed to characterize longitudinal progression of MTL atrophy in 93 individuals with subjective cognitive decline and mild cognitive impairment followed up over six years, and to assess if clinical rating scales are able to detect these changes. All MRI images were visually rated according to Scheltens' scale of medial temporal atrophy (MTA) by two neuroradiologists and AVRA, a software for automated MTA ratings. The images were also segmented using FreeSurfer's longitudinal pipeline in order to compare the MTA ratings to volumes of the hippocampi and inferior lateral ventricles. We found that MTL atrophy rates increased with CSF biomarker abnormality, used to define preclinical stages of Alzheimer's Disease. Both AVRA's and the radiologists' MTA ratings showed similar longitudinal trends as the subcortical volumes, suggesting that visual rating scales provide a valid alternative to automatic segmentations. Our results further showed that it took more than 8 years on average for individuals with mild cognitive impairment, and an Alzheimer's disease biomarker profile, to increase the MTA score by one. This suggests that discrete MTA ratings are too coarse for tracking individual MTL atrophy in short time spans. While the MTA scores from each radiologist showed strong correlations to subcortical volumes, the inter-rater agreement was low. We conclude that the main limitation of quantifying MTL atrophy with visual ratings in clinics is the subjectiveness of the assessment.

Fig. 1

Example of the Scheltens’ MTA scale, with progressive atrophy of the hippocampus, the choroid fissure and the inferior lateral ventricle. The image selected for each score was given the same rating by both radiologists in this study. Each hemisphere is rated individually.

Fig. 2

Violinplots of the radiologists’ MTA ratings and corresponding hippocampal volume (top) and inferior lateral ventricle volume (bottom). The width of the violins shows the distribution over volumes for each rating and rater, and the area indicates the number of images given a specific rating. The green dots show AVRA’s MTA rating for each image.

Fig. 3

Medial temporal lobe measures of the left hemisphere plotted against age at scan time for different combinations of A$\beta$ (A) and phosphorylated tau (T) abnormality. From the top: MTA ratings by Rad. 1; MTA ratings by Rad. 2; MTA ratings by AVRA; Hippocampal (HC) volumes; Inferior lateral ventricles (ILV) volumes. Orange and blue lines show individual trajectories for SCD and MCI patients, respectively. The green dots show if a patient was diagnosed with dementia at the given timepoint. A small random offset ($|\epsilon |<.175$) has been added to each individual’s Rad. 1 and Rad. 2 ratings to make it easier to distinguish between overlapping trajectories.

Fig. 4

Shows distribution (kernel density plots) of the change in HC (left) and ILV (right) volumes between baseline and follow-up scan. A follow-up image rated the same as the baseline scan are in blue (“0 MTA”), 1 MTA score higher (“+1 MTA”) in orange, and 2 MTA scores higher (“+2 MTA”) in green. Solid lines are ratings from Rad. 1 and dotted lines from Rad. 2.