Altered Frequency-Dependent Brain Activation and White Matter Integrity Associated With Cognition in Characterizing Preclinical Alzheimer's Disease Stages.

Siyu Wang,Wenying Ma,Guanjie Hu,Jiang Rao,Fuquan Zhang,Chen Xue,Yingying Yue,Honglin Ge,Xiangrong Zhang,Jiu Chen,Wenzhang Qi

doi:10.3389/fnhum.2021.625232

Abstract

BackgroundSubjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI) are regarded to be at high risk of converting to Alzheimer’s disease (AD). Amplitude of low-frequency fluctuations (ALFF) can reflect functional deterioration while diffusion tensor imaging (DTI) is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.MethodsWe analyzed ALFF under slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz) bands and white matter fiber integrity among normal controls (CN), SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.ResultsFor ALFF calculation, ascended ALFF values were detected in the lingual gyrus (LING) and superior frontal gyrus (SFG) within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus (UF) in aMCI patients and within the superior longitudinal fasciculus (SLF) in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.ConclusionsSCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression.

Highlights

Subjective cognitive decline (SCD), amnestic mild cognitive impairment, and non-amnestic mild cognitive impairment are regarded to be at high risk of converting to Alzheimer’s disease (AD) (Petersen et al, 2001, 2009; Jessen et al, 2014)
To the best of our knowledge, our study was the first to combine Amplitude of low-frequency fluctuations (ALFF) detection with diffusion tensor imaging (DTI) analyses and cognition to reveal the inner relationship of CN, SCD, non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI)
Our results discovered ascended ALFF values mainly in SCD and naMCI patients while descended ALFF values in aMCI patients in comparison with the other three groups. aMCI and naMCI patients reflected white matter alterations in the uncinate fasciculus (UF) and superior longitudinal fasciculus (SLF), respectively, while SCD patients exhibited alterations in both fasciculi

Summary

Introduction

Subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and non-amnestic mild cognitive impairment (naMCI) are regarded to be at high risk of converting to Alzheimer’s disease (AD) (Petersen et al, 2001, 2009; Jessen et al, 2014). Amplitude of low-frequency fluctuations (ALFF), defined by BOLD signal fluctuations under low frequency bands, is widely utilized in preclinical AD detection to reflect intrinsic neuronal activities (Lu et al, 2007; Hare et al, 2017). Subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI) are regarded to be at high risk of converting to Alzheimer’s disease (AD). Amplitude of low-frequency fluctuations (ALFF) can reflect functional deterioration while diffusion tensor imaging (DTI) is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration

Methods

Results

Discussion

Conclusion