Spatial correlation maps of the hippocampus with cerebrospinal fluid biomarkers and cognition in Alzheimer's disease: A longitudinal study

Abstract

This study is an observational study that takes the existing longitudinal data from Alzheimer's disease Neuroimaging Initiative to examine the spatial correlation map of hippocampal subfield atrophy with CSF biomarkers and cognitive decline in the course of AD. This study included 421 healthy controls (HC), 557 patients of stable mild cognitive impairment (s-MCI), 304 Alzheimer's Disease (AD) patients, and 241 subjects who converted to be AD from MCI (c-MCI), and 6,525 MRI scans in a period from 2004 to 2019. Our findings revealed that all the hippocampal subfields showed their accelerated atrophy rate from cognitively normal aging to stable MCI and AD. The presubiculum, dentate gyrus, and fimbria showed greater atrophy beyond the whole hippocampus in the HC, s-MCI, and AD groups and corresponded to a greater decline of memory and attention in the s-MCI group. Moreover, the higher atrophy rates of the subiculum and CA2/3, CA4 were also associated with a greater decline in attention in the s-MCI group. Interestingly, patients with c-MCI showed that the presubiculum atrophy was associated with CSF tau levels and corresponded to the onset age of AD and a decline in attention in patients with c-MCI. These spatial correlation findings of the hippocampus suggested that the hippocampal subfields may not be equally impacted by normal aging, MCI, and AD, and their atrophy was selectively associated with declines in specific cognitive domains. The presubiculum atrophy was highlighted as a surrogate marker for the AD prognosis along with tau pathology and attention decline.