Automated fiber quantification with white matter tract integrity metrics identified subtle changes in brain microstructure occurring in the early stages of Alzheimer’s pathology. These metrics were found to be significantly different in the posterior section of the parahippocampal white matter in cognitively normal older adults with hippocampal atrophy as compared to those without. Axonal water fraction distinguished those with hippocampal atrophy versus those without with the largest effect size (Cohen’s d = 0.86, p = 0.004). As expected, the metrics for these two groups did not differ in the arcuate fasciculus, a tract typically unaffected in Alzheimer’s disease.
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