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Background  Alzheimer’s disease (AD) is a progressive, incurable neurodegenerative disease and the most common type of dementia. It cannot be prevented, cured or drastically slowed, even though AD research has increased in the past 5-10 years. Instead of focusing on the brain volume or on the single brain structures like hippocampus, this paper investigates the relationship and proximity between regions in the brain and uses this information as a novel way of classifying normal control (NC), mild cognitive impaired (MCI), and AD subjects.    Methods  A longitudinal cohort of 528 subjects (170 NC, 240 MCI, and 114 AD) from ADNI at baseline and month 12 was studied. We investigated a marker based on Procrustes aligned center of masses and the percentile surface connectivity between regions. These markers were classified using a linear discriminant analysis in a cross validation setting and compared to whole brain and hippocampus volume.    Results  We found that both our markers was able to significantly classify the subjects. The surface connectivity marker showed the best results with an area under the curve (AUC) at 0.877 ( p <0.001), 0.784 ( p <0.001), 0,766 ( p <0.001) for NC-AD, NC-MCI, and MCI-AD, respectively, for the functional regions in the brain. The surface connectivity marker was able to classify MCI-converters with an AUC of 0.599 ( p <0.05) for the 1-year period.    Conclusion  Our results show that our relative proximity markers include more information than whole brain and hippocampus volume. Our results demonstrate that our proximity markers have the potential to assist in early diagnosis of AD.

Brain region’s relative proximity as marker for Alzheimer’s disease based on structural MRI