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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 Khondoker, Mizanur R. Grothe, Michel J. Teipel, Stefan Wright, Paul Heinsen, Helmut Jones, Derek Kenton Aggleton, John P. O'Sullivan, Michael J.
Ray, Nicola J.
Metzler-Baddeley, Claudia
Khondoker, Mizanur R.
Grothe, Michel J.
Teipel, Stefan
Wright, Paul
Heinsen, Helmut
Jones, Derek Kenton
Aggleton, John P.
O'Sullivan, Michael J.
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.
Keywords
cholinergic system, diffusion, episodic memory, fornix, mild cognitive impairment, white matter
Date
2015
Type
Journal article
Journal
Journal of Neuroscience
Book
Volume
35
Issue
2
Page Range
739-747
Article Number
ACU Department
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 3.0
File Access
Open
Notes
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.