Alteration of regional homogeneity and white matter hyperintensities in amnestic mild cognitive impairment subtypes are related to cognition and CSF biomarkers

Abstract

Amnestic mild cognitive impairment can be further classified as single-domain aMCI (SD-aMCI) with isolated memory deficit, or multi-domain aMCI (MD-aMCI) if memory deficit is combined with impairment in other cognitive domains. Prior studies reported these clinical subtypes presumably differ in etiology. Thus, we aimed to explore the possible mechanisms between different aMCI subtypes by assessing alteration in brain activity and brain vasculature, and their relations with CSF AD biomarkers. 49 healthy controls, 32 SD-aMCI, and 32 MD-aMCI, who had undergone structural scans, resting-state functional MRI (rsfMRI) scans and neuropsychological evaluations, were identified. Regional homogeneity (ReHo) was employed to analyze regional synchronization. Periventricular white matter hyperintensities (PWMH) and deep WMH (DWMH) volume of each participant was quantitatively assessed. AD biomarkers from CSF were also measured. SD-aMCI showed decreased ReHo in medial temporal gyrus (MTG), and increased ReHo in lingual gyrus (LG) and superior temporal gyrus (STG) relative to controls. MD-aMCI showed decreased ReHo, mostly located in precuneus (PCu), LG and postcentral gyrus (PCG), relative to SD-aMCI and controls. As for microvascular disease, MD-aMCI patients had more PWMH burden than SD-aMCI and controls. Correlation analyses indicated mean ReHo in differenced regions were related with memory, language, and executive function in aMCI patients. However, no significant associations between PWMH and behavioral data were found. The Aβ level was related with the ReHo value of STG in SD-aMCI. MD-aMCI displayed different patterns of abnormal regional synchronization and more severe PWMH burden compared with SD-aMCI. Therefore aMCI is not a uniform disease entity, and MD-aMCI group may show more complicated pathologies than SD-aMCI group.

Differential Regional Brain Spontaneous Activity in Subgroups of Mild Cognitive Impairment

“…The first important finding is higher fALFF in the left-sided superior-to-middle frontal gyri and middle-to-inferior temporal gyri in the sd-aMCI than both the md-aMCI and HC groups. The superior and middle frontal gyri are involved in a series of cognitive processes, such as executive function and working memory (Kim et al, 2014;Zamora et al, 2016), while the lateral temporal cortex is more involved in episodic memory (Luo et al, 2018). These cognitive functions are typically impaired in AD and MCI patients (Bell-McGinty et al, 2005;Clément and Belleville, 2010;Teipel et al, 2010;Liang et al, 2011;Scheller et al, 2014;Verfaillie et al, 2016;Melrose et al, 2018).…”

Decreased Bilateral FDG-PET Uptake and Inter-Hemispheric Connectivity in Multi-Domain Amnestic Mild Cognitive Impairment Patients: A Preliminary Study

“…However, only the MD-aMCI simultaneously displayed inter-hemispheric functional connectivity decrease in MTG, supporting the notion that the MD-aMCI is a more advanced disease form than the SD-aMCI. Notably, one study pointed out that SD-aMCI displayed decreased regional activity in right MTG relative to NC ( Luo et al, 2018a ). Accordingly, we speculated that the intact inter-hemispheric connectivity in SD-aMCI might compensate its unilateral MTL impairment to some extent.…”

Advances in Resting State Neuroimaging of Mild Cognitive Impairment

“…However, as MCI is a heterogeneous state, AD biomarker related approaches and detailed cognitive examinations may bear more fruit. A recent study combing rs-fMRI and CSF showed the ReHo value was associated with A β level in superior temporal gyrus in single domain MCI while the multiple-domain MCI exhibited a more complex pattern of pathology and functional activity (47).…”