King's College London

Research portal

Cholinergic Basal Forebrain Structure Influences the Reconfiguration of White Matter Connections to Support Residual Memory in Mild Cognitive Impairment

Research output: Contribution to journalArticle

N. J. Ray, C. Metzler-baddeley, M. R. Khondoker, M. J. Grothe, S. Teipel, P. Wright, H. Heinsen, D. K. Jones, J. P. Aggleton, Michael O'Sullivan

Original languageEnglish
Pages (from-to)739-747
Number of pages9
JournalJournal of Neuroscience
Volume35
Issue number2
DOIs
Publication statusPublished - 14 Jan 2015

Documents

  • Ray et al. 2015 J Neurosci

    cbf.pdf, 961 KB, application/pdf

    21/07/2015

    Final published version

    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

King's Authors

Abstract

The fornix and hippocampus are critical to recollection in the healthy human brain. Fornix degeneration is a feature of aging and Alzheimer's disease. In the presence of fornix damage in mild cognitive impairment (MCI), a recognized prodrome of Alzheimer's disease, recall shows greater dependence on other tracts, notably the parahippocampal cingulum (PHC). The current aims were to determine whether this shift is adaptive and to probe its relationship to cholinergic signaling, which is also compromised in Alzheimer's disease. Twenty-five human participants with MCI and 20 matched healthy volunteers underwent diffusion MRI, behavioral assessment, and volumetric measurement of the basal forebrain. In a regression model for recall, there was a significant group × fornix interaction, indicating that the association between recall and fornix structure was weaker in patients. The opposite trend was present for the left PHC. To further investigate this pattern, two regression models were generated to account for recall performance: one based on fornix microstructure and the other on both fornix and left PHC. The realignment to PHC was positively correlated with free recall but not non-memory measures, implying a reconfiguration that is beneficial to residual memory. There was a positive relationship between realignment to PHC and basal forebrain gray matter volume despite this region demonstrating atrophy at a group level, i.e., the cognitive realignment to left PHC was most apparent when cholinergic areas were relatively spared. Therefore, cholinergic systems appear to enable adaptation to injury even as they degenerate, which has implications for functional restoration.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454