Corpus Callosum Atrophy Rate in Mild Cognitive Impairment and Prodromal Alzheimer's Disease

Abstract

Background Corpus callosum (CC) size and shape have been previously studied in Alzheimer’s disease (AD) with the majority of studies having been cross-sectional. Due to the large variance in normal CC morphology, cross-sectional studies are limited in statistical power. Determining individual rates of change requires longitudinal data. Physiological changes are particularly relevant in mild cognitive impairment (MCI), in which CC morphology has not been previously studied longitudinally. Objective To study temporal rates of change in CC morphology in MCI patients over a one-year period, and to determine whether these rates differ between MCI subjects who converted to AD (MCI-C) and those who did not (MCI-NC) over an average (±SD) observation period of 5.4 (±1.6) years. Methods We used a novel multi-atlas based algorithm to segment the mid-sagittal cross-sectional area of the CC in longitudinal MRI scans. Rates of change of CC circularity, total area, and five sub-areas were compared between 57 MCI-NC and 81 MCI-C subjects. Results The CC became less circular (−0.89% per year in MCI-NC, −1.85% per year in MCI-C) with time, with faster decline in MCI-C (p=0.0002). In females, atrophy rates were higher in MCI-C relative to MCI-NC in total CC area (p=0.0006), genu/rostrum (p=0.005), and splenium (0.002). In males, these rates did not differ between groups. Conclusion A greater than normal decline in CC circularity was shown to be an indicator of prodromal AD in MCI subjects. This measure is potentially useful as an imaging biomarker of disease and a therapeutic target in clinical trials.

Predicting progression from mild cognitive impairment to Alzheimer's disease using longitudinal callosal atrophy

“…In contrast, the discriminating parts of CC in females were broader areas of the genu and/or rostrum, posterior body, and splenium. In general, these findings agree with a previous study [8] that measured differences in broad areas where CC was segmented into five regions. This article looks at differences on a much finer scale in discrimination analysis.…”

“…Elahi et al. [8] reported that changes in CC morphology were large enough to be detectable over a 1‐year period on structural MRI scans. The CC became less circular with time and with faster decline in MCI‐C.…”

“…To our knowledge, only one study has been published. Elahi et al [8] reported that changes in CC morphology were large enough to be detectable over a 1year period on structural MRI scans. The CC became less circular with time and with faster decline in MCI-C. Callosal atrophy rate was higher in female MCI-C relative to female MCI-NC, whereas in contrast, the rate did not differ between groups in males.…”

Prediction of Incipient Alzheimer’s Disease Dementia in Patients with Mild Cognitive Impairment

“…Additional biomarkers could for example be related to the size and shape of the corpus callosum derived from structural MRI which many studies have shown to be different between mild AD and normal subjects both in their baseline levels and rates of change longitudinally [49][50][51][52]. Other potential structural MRI biomarkers are measures of atrophy in the entorhinal cortex [53][54][55] and posterior cingulate [56,57].…”

Callosal thickness profiles for prognosticating conversion from mild cognitive impairment to Alzheimer’s disease: A classification approach

“…Midsagittal callosal area closely correlates with total myelinated axonal fiber count (Riise & Pakkenberg, ), and studies show greater thickness of the corpus callosum is linked to measures of general cognitive ability (Luders et al, ). To date, there has been one other study of CC morphology change with disease progression in ADNI (Elahi, Bachman, Lee, Sidtis, & Ardekani, ). This paper used regional area and circularity, a measure of bending, and showed statistically significant differences between MCI converters and nonconverters.…”