Altered Functional Connectivity of the Basal Nucleus of Meynert in Subjective Cognitive Impairment, Early Mild Cognitive Impairment, and Late Mild Cognitive Impairment

Abstract

Background: The spectrum of early Alzheimer's disease (AD) is thought to include subjective cognitive impairment, early mild cognitive impairment (eMCI), and late mild cognitive impairment (lMCI). Choline dysfunction affects the early progression of AD, in which the basal nucleus of Meynert (BNM) is primarily responsible for cortical cholinergic innervation. The aims of this study were to determine the abnormal patterns of BNM-functional connectivity (BNM-FC) in the preclinical AD spectrum (SCD, eMCI, and lMCI) and further explore the relationships between these alterations and neuropsychological measures.Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate FC based on a seed mask (BNM mask) in 28 healthy controls (HC), 30 SCD, 24 eMCI, and 25 lMCI patients. Furthermore, the relationship between altered FC and neurocognitive performance was examined by a correlation analysis. The receiver operating characteristic (ROC) curve of abnormal BNM-FC was used to specifically determine the classification ability to differentiate the early AD disease spectrum relative to HC (SCD and HC, eMCI and HC, lMCI and HC) and pairs of groups in the AD disease spectrum (eMCI and SCD, lMCI and SCD, eMCI and lMCI).Results: Compared with HC, SCD patients showed increased FC in the bilateral SMA and decreased FC in the bilateral cerebellum and middle frontal gyrus (MFG), eMCI patients showed significantly decreased FC in the bilateral precuneus, and lMCI individuals showed decreased FC in the right lingual gyrus. Compared with the SCD group, the eMCI group showed decreased FC in the right superior frontal gyrus (SFG), while the lMCI group showed decreased FC in the left middle temporal gyrus (MTG). Compared with the eMCI group, the lMCI group showed decreased FC in the right hippocampus. Interestingly, abnormal FC was associated with certain cognitive domains and functions including episodic memory, executive function, information processing speed, and visuospatial function in the disease groups. BNM-FC of SFG in distinguishing eMCI from SCD; BNM-FC of MTG in distinguishing lMCI from SCD; BNM-FC of the MTG, hippocampus, and cerebellum in distinguishing SCD from HC; and BNM-FC of the hippocampus and MFG in distinguishing eMCI from lMCI have high sensitivity and specificity.Conclusions: The abnormal BNM-FC patterns can characterize the early disease spectrum of AD (SCD, eMCI, and lMCI) and are closely related to the cognitive domains. These new and reliable findings will provide a new perspective in identifying the early disease spectrum of AD and further strengthen the role of cholinergic theory in AD.

Effects of Cigarette Smoking on Resting-State Functional Connectivity of the Nucleus Basalis of Meynert in Mild Cognitive Impairment

“…Based on the resting-state functional MRI (rsfMRI), the NBM showed decreased FC with the posterior cingulate cortex, precuneus, and cuneus in smokers as compared with non-smokers ( Zhang et al, 2017 ). Few studies also found decreased FC of the NBM to insula, precuneus, and lingual gyrus in MCI patients when compared with healthy control ( Li et al, 2017 ; Xu et al, 2021 ). However, how cigarette smoking affects the FC alterations of the NBM in MCI patients remains unclear.…”

Intrinsic Brain Activity Alterations in Patients With Mild Cognitive Impairment-to-Normal Reversion: A Resting-State Functional Magnetic Resonance Imaging Study From Voxel to Whole-Brain Level

“…However, its negative correlation with Rey Auditory Verbal Learning Test scores suggested that the functional improvement may not be directly subject to the recovery of MFG function. A potential effect may be mediated by the altered functional connection of MFG to the whole brain in reverters ( Veitch et al, 2019 ; Xu et al, 2021 ). Future studies are required to deeply investigate this possibility and clarify the relationship between alterations in intrinsic brain activity and cognitive reversion.…”

Inhibition of Astrocytic Histamine N-Methyltransferase as a Possible Target for the Treatment of Alzheimer’s Disease

“…ACh exerts its effects by binding to muscarinic (M1 to M5) and nicotinic receptors. Termination of acetylcholine action occurs when ACh is degraded by acetylcholinesterase (AChE) into choline and acetate [38].…”