Differential Abnormality in Functional Connectivity Density in Preclinical and Early-Stage Alzheimer's Disease

Abstract

BackgroundBoth subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) have a high risk of progression to Alzheimer's disease (AD). While most of the available evidence described changes in functional connectivity (FC) in SCD and aMCI, there was no confirmation of changes in functional connectivity density (FCD) that have not been confirmed. Therefore, the purpose of this study was to investigate the specific alterations in resting-state FCD in SCD and aMCI and further assess the extent to which these changes can distinguish the preclinical and early-stage AD.MethodsA total of 57 patients with SCD, 59 patients with aMCI, and 78 healthy controls (HC) were included. The global FCD, local FCD, and long-range FCD were calculated for each voxel to identify brain regions with significant FCD alterations. The brain regions with abnormal FCD were then used as regions of interest for FC analysis. In addition, we calculated correlations between neuroimaging alterations and cognitive function and performed receiver-operating characteristic analyses to assess the diagnostic effect of the FCD and FC alterations on SCD and aMCI.ResultsFCD mapping revealed significantly increased global FCD in the left parahippocampal gyrus (PHG.L) and increased long-range FCD in the left hippocampus for patients with SCD when compared to HCs. However, when compared to SCD, patients with aMCI showed significantly decreased global FCD and long-range FCD in the PHG.L. The follow-up FC analysis further revealed significant variations between the PHG.L and the occipital lobe in patients with SCD and aMCI. In addition, patients with SCD also presented significant changes in FC between the left hippocampus, the left cerebellum anterior lobe, and the inferior temporal gyrus. Moreover, changes in abnormal indicators in the SCD and aMCI groups were significantly associated with cognitive function. Finally, combining FCD and FC abnormalities allowed for a more precise differentiation of the clinical stages.ConclusionTo our knowledge, this study is the first to investigate specific alterations in FCD and FC for both patients with SCD and aMCI and confirms differential abnormalities that can serve as potential imaging markers for preclinical and early-stage Alzheimer's disease (AD). Also, it adds a new dimension of understanding to the diagnosis of SCD and aMCI as well as the evaluation of disease progression.

Functional and structural alterations of dorsal attention network in preclinical and early‐stage Alzheimer's disease

“…After normalization, they were regressed with the Friston 24‐parameter model and resampled 3 × 3 × 3 mm 3 into Montreal Neurological Institute (MNI). Finally, the fMRI data were spatially smoothed and temporal band‐pass filtered 32 …”

Altered anterior cingulate cortex subregional connectivity associated with cognitions for distinguishing the spectrum of pre-clinical Alzheimer’s disease

“…); (c) severe loss of sight or hearing; (d) inability to complete neuropsychological assessment or contraindications to MRI; and (e) T2-weighted MRI showing major changes in white matter (WM), infarction, or other lesions ( Chen et al, 2019 ). The above inclusion and exclusion criteria are similar to those used in our previous studies ( Chen et al, 2016b , 2019 , 2020 ; Xue et al, 2021 ; Song et al, 2022 ).…”

“…The above inclusion and exclusion criteria are similar to those used in our previous studies (Chen et al, 2016b(Chen et al, , 2019(Chen et al, , 2020Xue et al, 2021;Song et al, 2022).…”

Mapping brain networks in MPS I mice and their restoration following gene therapy

“…As temporal correlation of spontaneous BOLD fluctuation is assumed to be closely associated with neural synchronization 13 , rs-fMRI serves as an excellent surrogate of intrinsic brain activity from which spontaneous functional connectivity involving multiple brain regions can be identified to generate multiple resting state networks (RSNs) 14 – 20 . Clinically, rs-fMRI has identified a large number of RSNs that underlie various normal and pathophysiological behavioral states such as Alzheimer’s disease 21 , 22 , major depression 23 , 24 , and schizophrenia 25 . These studies demonstrate that deficits in neural network and interconnectivity are the underlying basis for specific neurological disorders.…”