Charting Brain Changes in Early Alzheimer’s with Functional Connectivity Density

Published on May 25, 2022

Imagine the brain as a bustling city. In the early stages of Alzheimer’s disease, some areas of this city experience abnormal connectivity patterns that may indicate the onset of cognitive decline. A recent study dived into how functional connectivity density (FCD) differs in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), two conditions with high risks of progressing to Alzheimer’s disease. The researchers found that individuals with SCD showed increased global FCD in the left parahippocampal gyrus and increased long-range FCD in the left hippocampus. On the other hand, patients with aMCI exhibited decreased global and long-range FCD in the same region. By examining the functional connectivity between these regions, they discovered additional significant variations. These distinct alterations in FCD and functional connectivity could potentially serve as imaging markers to aid in early diagnosis and tracking disease progression. To learn more about these fascinating brain changes and their implications for Alzheimer’s research, check out the full article!

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.

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