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 K., Aggleton, John P. 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: 739-747. doi:10.1523/JNEUROSCI.3617-14.2015

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Author Ray, Nicola J.
Metzler-Baddeley, Claudia
Khondoker, Mizanur R.
Grothe, Michel J.
Teipel, Stefan
Wright, Paul
Heinsen, Helmut
Jones, Derek K.
Aggleton, John P.
O'Sullivan, Michael J.
Title Cholinergic basal forebrain structure influences the reconfiguration of white matter connections to support residual memory in mild cognitive impairment
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 1529-2401
0270-6474
Publication date 2015-01-14
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.3617-14.2015
Open Access Status File (Publisher version)
Volume 35
Issue 2
Start page 739
End page 747
Total pages 9
Place of publication Washington, DC, United States
Publisher Society for Neuroscience
Language eng
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.
Keyword Cholinergic system
Diffusion
Episodic memory
Fornix
Mild cognitive impairment
White matter
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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