No relationship between fornix and cingulum degradation and within-network decreases in functional connectivity in prodromal Alzheimer's disease

• Published in: PloS one Vol. 14; no. 10; p. e0222977
• Main Authors: Gilligan, Therese M, Sibilia, Francesca, Farrell, Dervla, Lyons, Declan, Kennelly, Seán P, Bokde, Arun L W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.10.2019; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aging; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - physiopathology; Alzheimer's disease; Artificial neural networks; Atrophy; Attention deficit hyperactivity disorder; Biology and Life Sciences; Brain; Care and treatment; Cingulum; Cognitive ability; Computer and Information Sciences; Control methods; Correlation; Correlation analysis; Correlation coefficient; Correlation coefficients; Dementia; Diffusion Magnetic Resonance Imaging; Diffusion rate; Diffusivity; Female; Fornix; Fornix, Brain - diagnostic imaging; Fornix, Brain - physiopathology; Graph theory; Hemispheric laterality; Hippocampus; Humans; Internet; Magnetic resonance imaging; Male; Medicine; Medicine and Health Sciences; Memory; Nerve Net - diagnostic imaging; Nerve Net - physiopathology; Neural networks; Neuropsychological Tests; Neurosciences; NMR; Nuclear magnetic resonance; Parahippocampal gyrus; Physical Sciences; Psychiatry; Regression analysis; Rest; Risk factors; Social Sciences; Structure-function relationships; Substantia alba; Thalamus; White Matter - diagnostic imaging; White Matter - physiopathology; Ireland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0222977

The earliest changes in the brain due to Alzheimer's disease are associated with the neural networks related to memory function. We investigated changes in functional and structural connectivity among regions that support memory function in prodromal Alzheimer's disease, i.e., during the mild cognitive impairment (MCI) stage. Twenty-three older healthy controls and 25 adults with MCI underwent multimodal MRI scanning. Limbic white matter tracts-the fornix, parahippocampal cingulum, retrosplenial cingulum, subgenual cingulum and uncinate fasciculus-were reconstructed in ExploreDTI using constrained spherical deconvolution-based tractography. Using a network-of-interest approach, resting-state functional connectivity time-series correlations among sub-parcellations of the default mode and limbic networks, the hippocampus and the thalamus were calculated in Conn. Controlling for age, education, and gender between group linear regressions of five diffusion-weighted measures and of resting state connectivity measures were performed per hemisphere. FDR-corrections were performed within each class of measures. Correlations of within-network Fisher Z-transformed correlation coefficients and the mean diffusivity per tract were performed. Whole-brain graph theory measures of cluster coefficient and average path length were inspecting using the resting state data. MCI-related changes in white matter structure were found in the fornix, left parahippocampal cingulum, left retrosplenial cingulum and left subgenual cingulum. Functional connectivity decreases were observed in the MCI group within the DMN-a sub-network, between the hippocampus and sub-areas -a and -c of the DMN, between DMN-c and DMN-a, and, in the right hemisphere only between DMN-c and both the thalamus and limbic-a. No relationships between white matter tract 'integrity' (mean diffusivity) and within sub-network functional connectivity were found. Graph theory revealed that changes in the MCI group was mostly restricted to diminished between-neighbour connections of the hippocampi and of nodes within DMN-a and DMN-b.