Ghahremani Maryam, Nathan Santhosh, Smith Eric E, McGirr Alexander, Goodyear Bradley, Ismail Zahinoor
Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada.
Department of Psychiatry Cumming School of Medicine Calgary Alberta Canada.
Alzheimers Dement (N Y). 2023 Jan 18;9(1):e12371. doi: 10.1002/trc2.12371. eCollection 2023.
BACKGROUND: Mild behavioral impairment (MBI) is a syndrome that uses later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a group at high risk for incident dementia. MBI is associated with neurodegenerative disease markers in advance of syndromic dementia. Functional connectivity (FC) correlates of MBI are understudied and could provide further insights into mechanisms early in the disease course. We used resting-state functional magnetic resonance imaging (rs-fMRI) to test the hypothesis that FC within the default mode network (DMN) and salience network (SN) of persons with MBI (MBI+) is reduced, relative to those without (MBI-). METHODS: From two harmonized dementia-free cohort studies, using a score of ≥6 on the MBI Checklist to define MBI status, 32 MBI+ and 63 MBI- individuals were identified (mean age: 71.7 years; 54.7% female). Seed-based connectivity analysis was implemented in each MBI group using the CONN fMRI toolbox (v20.b), with the posterior cingulate cortex (PCC) as the seed region within the DMN and anterior cingulate cortex (ACC) as the seed within the SN. The average time series from the PCC and ACC were used to determine FC with other regions within the DMN (medial prefrontal cortex, lateral inferior parietal cortex) and SN (anterior insula, supramarginal gyrus, rostral prefrontal cortex), respectively. Age, sex, years of education, and Montreal Cognitive Assessment scores were included as model covariates. The false discovery rate approach was used to correct for multiple comparisons, with a -value of .05 considered significant. RESULTS: For the DMN, MBI+ individuals exhibited reduced FC between the PCC and the medial prefrontal cortex, compared to MBI-. For the SN, MBI+ individuals exhibited reduced FC between the ACC and left anterior insula. CONCLUSION: MBI in dementia-free older adults is associated with reduced FC in networks known to be disrupted in dementia. Our results complement the evidence linking MBI with Alzheimer's disease biomarkers. HIGHLIGHTS: Resting-state functional magnetic resonance imaging was completed in 95 dementia-free persons from FAVR and COMPASS-ND studies.Participants were stratified by informant-rated Mild Behavioral Impairment Checklist (MBI-C) score, ≥6 for MBI+.MBI+ participants showed reduced functional connectivity (FC) within the default mode network and salience network.These FC changes are consistent with those seen in early-stage Alzheimer's disease.MBI may help identify persons with early-stage neurodegenerative disease.
背景:轻度行为障碍(MBI)是一种综合征,它利用晚年出现并持续存在的神经精神症状(NPS)来识别一组患痴呆症风险较高的人群。MBI在症状性痴呆出现之前就与神经退行性疾病标志物相关。MBI的功能连接(FC)相关性研究较少,可能会为疾病早期机制提供进一步见解。我们使用静息态功能磁共振成像(rs-fMRI)来检验以下假设:与无MBI者(MBI-)相比,患有MBI者(MBI+)的默认模式网络(DMN)和突显网络(SN)内的FC降低。 方法:从两项统一的无痴呆队列研究中,使用MBI清单评分≥6来定义MBI状态,确定了32名MBI+个体和63名MBI-个体(平均年龄:71.7岁;54.7%为女性)。使用CONN fMRI工具箱(v20.b)在每个MBI组中进行基于种子的连接性分析,以扣带回后部皮质(PCC)作为DMN内的种子区域,前扣带回皮质(ACC)作为SN内的种子。分别使用来自PCC和ACC的平均时间序列来确定与DMN(内侧前额叶皮质、外侧顶下小叶皮质)和SN(前岛叶、缘上回、前额叶皮质喙部)内其他区域的FC。年龄、性别、受教育年限和蒙特利尔认知评估得分作为模型协变量纳入。采用错误发现率方法校正多重比较,P值<0.05被认为具有统计学意义。 结果:对于DMN,与MBI-个体相比,MBI+个体在PCC和内侧前额叶皮质之间的FC降低。对于SN,MBI+个体在ACC和左侧前岛叶之间的FC降低。 结论:无痴呆的老年人中的MBI与痴呆中已知会被破坏的网络中FC降低有关。我们的结果补充了将MBI与阿尔茨海默病生物标志物联系起来的证据。 要点:对来自FAVR和COMPASS-ND研究的95名无痴呆者进行了静息态功能磁共振成像。参与者根据 informant 评定的轻度行为障碍清单(MBI-C)评分进行分层,MBI+评分≥6。MBI+参与者在默认模式网络和突显网络内的功能连接(FC)降低。这些FC变化与早期阿尔茨海默病中所见的变化一致。MBI可能有助于识别早期神经退行性疾病患者。
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