Analysis of the MIRIAD Data Shows Sex Differences in Hippocampal Atrophy Progression

Abstract

BACKGROUND: Hippocampus (HC) atrophy is a hallmark of early Alzheimer's disease (AD). Atrophy rates can be measured by high-resolution structural MRI. Longitudinal studies have previously shown sex differences in the progression of functional and cognitive deficits and rates of brain atrophy in early AD dementia. It is important to corroborate these findings on independent datasets. OBJECTIVE: To study temporal rates of HC atrophy over a one-year period in probable AD patients and cognitively normal (CN) subjects by longitudinal MRI scans obtained from the Minimal Interval Resonance Imaging in AD (MIRIAD) database. METHODS: We used a novel algorithm to compute an index of hippocampal (volumetric) integrity (HI) at baseline and one-year follow-up in 43 mild-moderate probable AD patients and 22 CN subjects in MIRIAD. The diagnostic power of longitudinal HI measurement was assessed using a support vector machines (SVM) classifier. RESULTS: The HI was significantly reduced in the AD group (p < 10(-20)). In addition, the annualized percentage rate of reduction in HI was significantly greater in the AD group (p < 10(-13)). Within the AD group, the annual reduction of HI in women was significantly greater than in men (p = 0.008). The accuracy of SVM classification between AD and CN subjects was estimated to be 97% by 10-fold cross-validation. CONCLUSION: In the MIRIAD patients with probable AD, the HC atrophies at a significantly faster rate in women as compared to men. Female sex is a risk factor for faster descent into AD. The HI measure has potential for AD diagnosis, as a biomarker of AD progression and a therapeutic target in clinical trials.