Abstract
Background: Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI). The basal nucleus of Meynert (BNM) provides the main source of cortical cholinergic innervation. Previous studies have characterized structural changes of the cholinergic basal forebrain in individuals at risk of developing Alzheimer’s disease (AD). However, whether and how functional connectivity of the BNM (BNM-FC) is altered in MCI remains unknown.Objective: The aim of this study was to identify alterations in BNM-FC in individuals with MCI as compared to healthy controls (HCs), and to examine the relationship between these alterations with neuropsychological measures in individuals with MCI.Method: One-hundred-and-one MCI patients and 103 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were processed with SPM8 and CONN software. BNM-FC was examined via correlation in low frequency fMRI signal fluctuations between the BNM and all other brain voxels. Group differences were examined with a covariance analysis with age, gender, education level, mean framewise displacement (FD) and global correlation (GCOR) as nuisance covariates. Pearson’s correlation was conducted to evaluate the relationship between the BNM-FC and clinical assessments.Result: Compared with HCs, individuals with MCI showed significantly decreased BNM-FC in the left insula extending into claustrum (insula/claustrum). Furthermore, greater decrease in BNM-FC with insula/claustrum was associated with more severe impairment in immediate recall during Auditory Verbal Learning Test (AVLT) in MCI patients.Conclusion: MCI is associated with changes in BNM-FC to the insula/claustrum in relation to cognitive impairments. These new findings may advance research of the cholinergic bases of cognitive dysfunction during healthy aging and in individuals at risk of developing AD.
Highlights
Mild cognitive impairment (MCI), as a syndrome of cognitive decline without demonstrable alteration in daily activities (Gauthier et al, 2006), frequently precedes the development of Alzheimer’s disease (AD; Petersen, 2011)
mild cognitive impairment (MCI) patients met the core clinical criteria stipulated by the National Institute on Aging and the Alzheimer’s Association (Albert et al, 2011) that include: (a) complaint of a change in cognition; (b) impairment in cognitive function, especially episodic memory; (c) ability to maintain independence in daily activities; (d) not demented; and (e) Clinical Dementia Rating (CDR) score = 0.5, with a score of at least 0.5 on the memory domain (Petersen et al, 2001)
Within group analysis revealed that the positive connectivity between the basal nucleus of Meynert (BNM) and many brain regions both in healthy controls (HCs) and individuals with MCI
Summary
Mild cognitive impairment (MCI), as a syndrome of cognitive decline without demonstrable alteration in daily activities (Gauthier et al, 2006), frequently precedes the development of Alzheimer’s disease (AD; Petersen, 2011). As the most important component of the basal forebrain cholinergic system (BFCS; Liu et al, 2015), the basal nucleus of Meynert (BNM) provides main sources of cholinergic innervation to the cerebral cortex (Gratwicke et al, 2013). In MCI, β-amyloid (Aβ) deposition, neurofibrillary tangles and trophic support reduction impair cholinergic functions of the BNM (Mesulam et al, 1986; Ruberg et al, 1990; Vogels et al, 1990). Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI). The basal nucleus of Meynert (BNM) provides the main source of cortical cholinergic innervation. Whether and how functional connectivity of the BNM (BNM-FC) is altered in MCI remains unknown
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