Rostral-Caudal Hippocampal Functional Convergence Is Reduced Across the Alzheimer's Disease Spectrum

Mol Neurobiol. 2019 Dec;56(12):8336-8344. doi: 10.1007/s12035-019-01671-0. Epub 2019 Jun 22.


Beginning in the early stages of Alzheimer's disease (AD), the hippocampus reduces its functional connections to other cortical regions due to synaptic depletion. However, little is known regarding connectivity abnormalities within the hippocampus. Here, we describe rostral-caudal hippocampal convergence (rcHC), a metric of the overlap between the rostral and caudal hippocampal functional networks, across the clinical spectrum of AD. We predicted a decline in rostral-caudal hippocampal convergence in the early stages of the disease. Using fMRI, we generated resting-state hippocampal functional networks across 56 controls, 48 early MCI (EMCI), 35 late MCI (LMCI), and 31 AD patients from the Alzheimer's Disease Neuroimaging Initiative cohort. For each diagnostic group, we performed a conjunction analysis and compared the rostral and caudal hippocampal network changes using a mixed effects linear model to estimate the convergence and differences between these networks, respectively. The conjunction analysis showed a reduction of rostral-caudal hippocampal convergence strength from early MCI to AD, independent of hippocampal atrophy. Our results demonstrate a parallel between the functional convergence within the hippocampus and disease stage, which is independent of brain atrophy. These findings support the concept that network convergence might contribute as a biomarker for connectivity dysfunction in early stages of AD.

Keywords: Alzheimer’s disease; Brain network; Functional connectivity; Hippocampus; Mild cognitive impairment.

MeSH terms

  • Aged
  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / physiopathology*
  • Case-Control Studies
  • Cognitive Dysfunction / complications
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / physiopathology*
  • Humans
  • Male
  • Neuroimaging
  • Severity of Illness Index