52 Open Access, Normative Morphometric Software Indicate Neurodegeneration Associated with Episodic Memory Dysfunction in Amnestic MCI

Abstract

Objective:

Neurodegeneration in Alzheimer’s disease (AD) is typically assessed through brain MRI, and proprietary software can provide normative quantification of regional atrophy. However, proprietary software can be cost-prohibitive for research settings. Thus, we used the freely available software NOrmative Morphometry Image Statistics (NOMIS) which generates normative z-scores of segmented T1-weighted images from FreeSurfer to determine if these scores replicate established patterns of neurodegeneration in the context of amnestic mild cognitive impairment (aMCI), and whether these measures correlate with episodic memory test performance.

Participants and Methods:

Patients with aMCI (n = 25) and cognitively normal controls (CN; n = 74) completed brain MRI and two neuropsychological tests of episodic memory (the Rey Auditory Verbal Learning Test and the Wechsler Logical Memory Tests I & II), from which a single composite of normed scores was computed. A subset returned for follow-up (aMCI n = 11, CN n = 52) after ∼15 months and completed the same procedures. T1-weighted images were segmented using FreeSurfer v6.0 and the outputs were submitted to NOMIS to generate normative morphometric estimates for AD-relevant regions (i.e., hippocampus, parahippocampus, entorhinal cortex, amygdala) and control regions (i.e., cuneus, lingual gyrus, pericalcarine gyrus), controlling for age, sex, head size, scanner manufacturer, and field strength. Baseline data were used to test for differences in ROI volumes and memory between groups and to assess the within-group associations between ROI volumes and memory performance. We also evaluated changes in ROI volumes and memory over the follow-up interval by testing the main effects of time, group, and the group X time interactions. Lastly, we tested whether change in volume was associated with declines in memory.

Results:

At baseline, the aMCI group performed 2 SD below the CN group on episodic memory and exhibited smaller volumes in all AD-relevant regions (volumes 0.4 - 1.2 SD below CN group, ps < .041). There were no group differences in control region volumes. Memory performance was associated with volumes of the AD-relevant regions in the aMCI group (average rho = .51) but not with control regions. ROI volumes were not associated with memory in the CN group. At follow-up, the aMCI group continued to perform 2 SD below the CN group on episodic memory tests; however, change of performance over time did not differ between groups. The aMCI group continued to exhibit smaller volumes in all AD-relevant regions than the CN group, with greater declines in hippocampal volume (17% annual decline vs. 8% annual decline) and entorhinal volume (54% annual decline vs. 5% annual decline). There was a trending Group X Time interaction such that decrease in hippocampal volume was marginally associated with decline in memory for the aMCI group but not the CN group.

Conclusions:

Normative morphometric values generated from freely available software demonstrated expected patterns of group differences in AD-related volumes and associations with memory. Significant effects were localized to AD-relevant brain regions and only occurred in the aMCI group. These findings support the validity of these free tools as reliable and cost-effective alternatives to proprietary software.