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

Autoři: Therese M. Gilligan aff001;  Francesca Sibilia aff001;  Dervla Farrell aff001;  Declan Lyons aff003;  Seán P. Kennelly aff002;  Arun L. W. Bokde aff001
Působiště autorů: Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland aff001;  Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland aff002;  St Patrick’s University Hospital, Dublin, Ireland aff003;  Discipline of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, Ireland aff004;  Memory Assessment and Support Service, Department of Age-related Healthcare, Tallaght University Hospital, Dublin, Ireland aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



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.

Results & conclusion

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.

Klíčová slova:

Alzheimer's disease – Atrophy – Central nervous system – Cognitive impairment – Graph theory – Hippocampus – Neuropsychological testing – Right hemisphere


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