Altered nucleus basalis connectivity predicts treatment response in mild cognitive impairment

Meng, Dewen; Li, Xingfeng; Bauer, Markus; Taylor, John-Paul; Auer, Dorothee P.; Alzheimer's Disease Neuroimaging Initiative

Abstract

Purpose: To determine whether functional connectivity (FC) mapping of nucleus basalis of Meynert (NBM) cholinergic network (hereafter, NBM FC) could provide a biomarker of central cholinergic deficits with predictive potential for response to cholinesterase inhibitor (ChEI) treatment.
Materials and Methods: The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was approved by the institutional review boards of all participating sites. All participants and their representatives gave written informed consent prior to data collection. NBM FC was examined in 33 healthy control participants, 102 patients with mild cognitive impairment (MCI), and 33 patients with AD by using resting-state functional MRI data from the ADNI database. NBM FC was compared between groups before and after 6 months of ChEI treatment in MCI. Associations between baseline NBM FC and baseline cognitive performance as well as cognitive outcomes after treatment were investigated.
Results: Compared with the healthy control group, NBM FC was decreased in patients with untreated MCI and increased in patients with AD treated with ChEI (corrected P ˂ .05). Global cognition (Alzheimer’s Disease Assessment Scale-Cognitive subscale score) was associated with NBM FC (r = −0.349; P ˂ .001). NBM FC was higher 6 months after ChEI compared with before ChEI in treated MCI (corrected P ˂ .05), but did not change at 6 months in patients with untreated MCI (corrected P ˂ .05). Baseline NBM FC in MCI strongly predicted cognitive outcomes 6 months after ChEI (R2 = 0.458; P = .001).
Conclusion: Functional dissociation of the nucleus basalis of Meynert from a cortical network may explain the cognitive deficits in dementia and allow for the selection of individuals who are more likely to respond to cholinesterase inhibitors at early disease stages.

Citation

Meng, D., Li, X., Bauer, M., Taylor, J., Auer, D. P., & Alzheimer's Disease Neuroimaging Initiative. (2018). Altered nucleus basalis connectivity predicts treatment response in mild cognitive impairment. Radiology, 289(3), 775-785. https://doi.org/10.1148/radiol.2018180092

• Journal Article Type: Article
• Acceptance Date: Jul 18, 2018
• Online Publication Date: Sep 11, 2018
• Publication Date: 2018-12
• Deposit Date: Oct 24, 2018
• Publicly Available Date: Mar 12, 2019
• Journal: Radiology
• Print ISSN: 0033-8419
• Electronic ISSN: 1527-1315
• Publisher: Radiological Society of North America
• Peer Reviewed: Peer Reviewed
• Volume: 289
• Issue: 3
• Pages: 775-785
• DOI: https://doi.org/10.1148/radiol.2018180092
• Keywords: Radiology Nuclear Medicine and imaging
• Public URL: https://nottingham-repository.worktribe.com/output/1184782
• Publisher URL: https://pubs.rsna.org/doi/10.1148/radiol.2018180092