PMID- 35693335 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1663-4365 (Print) IS - 1663-4365 (Electronic) IS - 1663-4365 (Linking) VI - 14 DP - 2022 TI - Differential Abnormality in Functional Connectivity Density in Preclinical and Early-Stage Alzheimer's Disease. PG - 879836 LID - 10.3389/fnagi.2022.879836 [doi] LID - 879836 AB - BACKGROUND: Both 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. METHODS: A 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. RESULTS: FCD 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. CONCLUSION: To 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. CI - Copyright (c) 2022 Song, Wu, Chen, Ge, Yan, Xue, Qi, Yuan, Liang, Lin and Chen. FAU - Song, Yu AU - Song Y AD - Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Wu, Huimin AU - Wu H AD - Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Chen, Shanshan AU - Chen S AD - Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Ge, Honglin AU - Ge H AD - Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. AD - Institute of Brain Functional Imaging, Nanjing Medical University, Nanjing, China. FAU - Yan, Zheng AU - Yan Z AD - Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. AD - Institute of Brain Functional Imaging, Nanjing Medical University, Nanjing, China. FAU - Xue, Chen AU - Xue C AD - Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Qi, Wenzhang AU - Qi W AD - Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Yuan, Qianqian AU - Yuan Q AD - Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Liang, Xuhong AU - Liang X AD - Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Lin, Xingjian AU - Lin X AD - Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. FAU - Chen, Jiu AU - Chen J AD - Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. AD - Institute of Brain Functional Imaging, Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article DEP - 20220525 PL - Switzerland TA - Front Aging Neurosci JT - Frontiers in aging neuroscience JID - 101525824 PMC - PMC9177137 OTO - NOTNLM OT - amnestic mild cognitive impairment OT - functional connectivity OT - functional connectivity density OT - functional magnetic resonance imaging OT - subjective cognitive decline COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/06/14 06:00 MHDA- 2022/06/14 06:01 PMCR- 2022/01/01 CRDT- 2022/06/13 03:14 PHST- 2022/02/20 00:00 [received] PHST- 2022/04/27 00:00 [accepted] PHST- 2022/06/13 03:14 [entrez] PHST- 2022/06/14 06:00 [pubmed] PHST- 2022/06/14 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fnagi.2022.879836 [doi] PST - epublish SO - Front Aging Neurosci. 2022 May 25;14:879836. doi: 10.3389/fnagi.2022.879836. eCollection 2022.