Hippocampus’ co-atrophy pattern in dementia deviates from covariance patterns across the lifespan

Brain.

ABSTRACT: The hippocampus is a plastic region and highly susceptible to aging and dementia. Previous studies explicitly imposed apriori models of hippocampus when investigating aging and dementia specific atrophy but led to inconsistent results. Consequently, the basic question of whether macro-structural changes follow a cytoarchitectonic or functional organization across the adult lifespan and in age-related neurodegenerative disease remained open. The aim of this cross-sectional study was to identify the spatial pattern of hippocampus differentiation based on structural covariance (SC) with a data-driven approach across structural MRI data of large cohorts. We examined the pattern of SC of hippocampus’ voxels in young, middle-aged, elderly, mild cognitive impairment and dementia disease samples by applying a clustering algorithm revealing differentiation in SC within the hippocampus. In all the healthy and in the MCI participants, the hippocampus was robustly divided into anterior, lateral and medial subregions reminiscent of cytoarchitectonic division. In contrast, in dementia patients, the pattern of subdivision was closer to known functional differentiation into an anterior, body and tail subregions. These results not only contribute to a better understanding of co-plasticity and co-atrophy in the hippocampus across the lifespan and in dementia, but also provide robust data-driven spatial representations (i.e. maps) for structural studies.