White Matter Hyperintensities Relate to Basal Ganglia Functional Connectivity and Memory Performance in aMCI and SVMCI.

Alaka Acharya,Xia Liang,Ying Han,Chuanlu Jiang,Liye Yi,Weiming Tian

doi:10.3389/fnins.2019.01204

Abstract

Cerebral small vessel diseases play a crucial role in both vascular and non-vascular dementias. The location of white matter hyperintensities (WMHs), a neuroimaging marker of cerebral small vessel disease, has been found to vary between different types of dementias, and those in the basal ganglia (BG) have been particularly associated with vascular cognitive impairment (VCI). However, anatomical variation of WMHs across BG nuclei and its effect on brain network dysconnectivity has not been clearly elucidated. The study sample consisted of 40 patients with amnestic mild cognitive impairment (aMCI), 40 with subcortical vascular MCI (SVMCI), and 40 healthy control subjects. We examined the volume of WMH using T2-weighted magnetic resonance imaging. We also assessed the disturbances in BG-cortical communication by measuring resting-state functional connectivity (rsFC) from the functional magnetic resonance imaging signal. WMHs were more pronounced in the SVMCI group particularly in the caudate regions. In SVMCI patients, while higher WMHs in the dorsal caudate correlated with weaker FC with executive control regions and worse immediate recall performance, WMHs in the ventral caudate were associated with weaker FC with anterior default mode regions and worse delayed recall performance. In contrast, in aMCI patients, BG WMHs were not correlated with their changes in functional connectivity changes, which showed weaker connectivity with almost all BG structures, rather than restricting to specific BG subdivisions as observed in the SVMCI group. Our findings demonstrate that heterogeneously distributed BG WMHs are associated with changes in functional network interactions and verbal episodic memory performance only in SVMCI patients, which establishes a link between cerebrovascular-related structural abnormality, functional integrity of BG circuits, and episodic memory impairments in SVMCI, and may reflect a differential role of the cerebrovascular pathology in disrupting network-level communications and cognition between Alzheimer’s and subcortical vascular dementia.

Highlights

Cerebral small vessel disease (SVD) are considered the primary cause of vascular cognitive impairment (VCI) (Chui, 2007; Pantoni, 2010) and are increasingly recognized to be involved in the etiology of traditionally “non-vascular” dementia of Alzheimer’s disease (AD) (Kalaria and Ihara, 2013; O’Brien and Markus, 2014)
To control for potential confounding effects of the Mini-Mental State Examination (MMSE) difference between the two MCI subgroups, we repeated our main analyses using a subgroup of the amnestic mild cognitive impairment (aMCI) patients whose MMSE scores matched with the subcortical vascular MCI (SVMCI) groups (SVMCI: n = 40; aMCI: n = 29, P = 0.78) and validated if the differences between MCI groups represent effects solely by MCI subtype
The current study revealed that, both aMCI and SVMCI patients appeared to have greater white matter hyperintensities (WMHs), SVMCI patients are characterized by more severe WMH impairments in basal ganglia (BG) areas

Summary

Introduction

Cerebral small vessel disease (SVD) are considered the primary cause of vascular cognitive impairment (VCI) (Chui, 2007; Pantoni, 2010) and are increasingly recognized to be involved in the etiology of traditionally “non-vascular” dementia of Alzheimer’s disease (AD) (Kalaria and Ihara, 2013; O’Brien and Markus, 2014). Chronic ischemia caused by SVD is often clinically characterized by white matter hyperintensities (WMHs) seen on magnetic resonance imaging (MRI) scans. The BG are a series of subcortical nucleus that can be divided into different divisions, with projections to cortical structures contributing to diverse brain functions (Alexander, 1986; Redgrave et al, 2010; Nelson and Kreitzer, 2014). What has not been tested, is whether WMH contents of different BG subdivisions, in the context of their marked anatomical and functional diversities, are differentially vulnerable to VCI

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