The diffeomorphometry of regional shape change rates and its relevance to cognitive deterioration in mild cognitive impairment and Alzheimer's disease.

We proposed a diffeomorphometry-based statistical pipeline to study the regional shape change rates of the bilateral hippocampus, amygdala, and ventricle in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with healthy controls (HC), using sequential magnetic resonance imaging (MRI) scans of 713 subjects (3,123 scans in total). The subgroup shape atrophy rates of the bilateral hippocampus and amygdala, as well as the expansion rates of the bilateral ventricles, for a majority of vertices were found to follow the order of AD>MCI>HC. The bilateral hippocampus and the left amygdala were subsegmented into multiple functionally meaningful subregions with the help of high-field MRI scans. The largest group differences in localized shape atrophy rates on the hippocampus were found to occur in CA1, followed by subiculum, CA2, and finally CA3/dentate gyrus, which is consistent with the neurofibrillary tangle accumulation trajectory. Highly nonuniform group differences were detected on the amygdala; vertices on the core amygdala (basolateral and lateral nucleus) revealed much larger atrophy rates, whereas those on the noncore amygdala (mainly centromedial) displayed similar or even smaller atrophy rates in AD relative to HC. The temporal horns of the ventricles were observed to have the largest localized ventricular expansion rate differences; with the AD group showing larger localized expansion rates on the anterior horn and the body part of the ventricles as well. Significant correlations were observed between the localized shape change rates of each of these six structures and the cognitive deterioration rates as quantified by the Alzheimer's Disease Assessment Scale-Cognitive Behavior Section increase rate and the Mini Mental State Examination decrease rate.