Neurodegeneration in Alzheimer’s disease (AD) is typically assessed through brain MRI. Although proprietary software can provide normative estimates of regional atrophy, such tools can be cost-prohibitive for research settings. Free software for generating normative estimates has recently been released but has yet to be validated in the context of amnestic mild cognitive impairment (aMCI).

Determine whether normative morphometric estimates generated from open-source software replicate established patterns of neurodegeneration in aMCI, and whether these metrics correlate with episodic memory performance.

Observational study of brain MRI and cognition in aging and aMCI with two identical study visits occurring approximately 1.2 years apart.

Participants were recruited from the local community and outpatient clinical settings.

Adults ages 60–85 with aMCI (n = 25) and cognitively normal controls (CN; n = 74). A subset returned for follow-up (aMCI n = 11, CN n = 52).

Participants completed brain MRI and two neuropsychological tests of verbal episodic memory. FreeSurfer v6.0 and Normative Morphometry Image Statistics were used to generate normative morphometric estimates for AD-relevant regions (hippocampus, parahippocampus, entorhinal cortex, amygdala) and control regions (cuneus, lingual gyrus, pericalcarine gyrus), adjusting for age, sex, head size, scanner manufacturer, and field strength. We tested for baseline group differences in ROI volumes and memory and assessed their within-group associations. We also evaluated changes in ROI volumes over time and tested whether these changes corresponded to declines in memory.

At baseline, the aMCI group exhibited poorer memory and smaller volumes in AD-relevant regions than the CN group. There were no group differences in control region volumes. Memory was associated with volumes in AD-relevant regions in the aMCI group only. The aMCI group exhibited greater declines than the CN group in hippocampal volume (17% vs. 8% annual decline) and entorhinal volume (54% vs. 5% annual decline). Decrease in hippocampal volume was marginally associated with decline in memory for the aMCI group.

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 for use in research settings.