Cholinergic basal forebrain structure influences the reconfiguration of white matter connections to support residual memory in mild cognitive impairment

Ray, Nicola J., Metzler-Baddeley, Claudia ORCID: https://orcid.org/0000-0002-8646-1144, Khondoker, Mizanur R., Grothe, Michel J., Teipel, Stefan, Wright, Paul, Heinsen, Helmut, Jones, Derek K. ORCID: https://orcid.org/0000-0003-4409-8049, Aggleton, John P. ORCID: https://orcid.org/0000-0002-5573-1308 and O'Sullivan, Michael J. 2015. Cholinergic basal forebrain structure influences the reconfiguration of white matter connections to support residual memory in mild cognitive impairment. Journal of Neuroscience 35 (2) , pp. 739-747. 10.1523/JNEUROSCI.3617-14.2015

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Psychology Cardiff University Brain Research Imaging Centre (CUBRIC) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	This article is freely available online through the J Neurosci Author Open Choice option.
Publisher:	Society for Neuroscience
ISSN:	1529-2401
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	12 November 2014
Last Modified:	11 May 2023 01:52
URI:	https://orca.cardiff.ac.uk/id/eprint/67333

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