Disrupted functional connectivity of the locus coeruleus in healthy adults with parental history of Alzheimer's disease.,Journal of Psychiatric Research

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Disrupted functional connectivity of the locus coeruleus in healthy adults with parental history of Alzheimer's disease.
Journal of Psychiatric Research ( IF 3.7 ) Pub Date : 2020-01-30 , DOI: 10.1016/j.jpsychires.2020.01.018
Inés Del Cerro ₁ , Mirta F Villarreal ₂ , Carolina Abulafia ₃ , Bárbara Duarte-Abritta ₃ , Stella M Sánchez ₃ , Mariana N Castro ₄ , Hernán Bocaccio ₃ , Isidre Ferrer ₅ , José Manuel Menchón ₁ , Gustavo Sevlever ₆ , Charles B Nemeroff ₇ , Carles Soriano-Mas ₈ , Salvador M Guinjoan ₄

Affiliation

Bellvitge Biomedical Research Institute-IDIBELL, Department of Psychiatry, Bellvitge University Hospital, Feixa Llarga S/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Bellvitge Campus, Barcelona University, Faculty of Medicine, Feixa Llarga, S/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain; Network Center for Biomedical Research on Mental Health (CIBERSAM), Av. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain.
Grupo de Investigación en Neurociencias Aplicadas a Las Alteraciones de La Conducta (INAAC), FLENI, Montañeses, 2325, Ciudad Autónoma de Buenos Aires, Argentina; Department of Physics, University of Buenos Aires. Pabellón I, Ciudad Universitaria, 1428, Ciudad Autónoma de Buenos Aires, Argentina; National Council for Scientific and Technological Research (CONICET), Godoy Cruz, 2290, Ciudad Autónoma de Buenos Aires, Argentina.
Grupo de Investigación en Neurociencias Aplicadas a Las Alteraciones de La Conducta (INAAC), FLENI, Montañeses, 2325, Ciudad Autónoma de Buenos Aires, Argentina; National Council for Scientific and Technological Research (CONICET), Godoy Cruz, 2290, Ciudad Autónoma de Buenos Aires, Argentina.
Grupo de Investigación en Neurociencias Aplicadas a Las Alteraciones de La Conducta (INAAC), FLENI, Montañeses, 2325, Ciudad Autónoma de Buenos Aires, Argentina; National Council for Scientific and Technological Research (CONICET), Godoy Cruz, 2290, Ciudad Autónoma de Buenos Aires, Argentina; Department of Psychiatry, FLENI and Department of Psychiatry and Mental Health, School of Medicine, University of Buenos Aires, Montañeses, 2325, Ciudad Autónoma de Buenos Aires, Argentina.
Department of Pathology and Experimental Therapeutics, Institute of Neurosciences, University of Barcelona, Facultad de Medicina y Ciencias de La Salud, Campus de Bellvitge, Pavelló de Govern, Feixa Llarga, S/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute-IDIBELL, Department of Pathologic Anatomy, Bellvitge University Hospital, Feixa Llarga S/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain; Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Valderrebollo, 5, 28031, Madrid, Spain.
National Council for Scientific and Technological Research (CONICET), Godoy Cruz, 2290, Ciudad Autónoma de Buenos Aires, Argentina; Department of Molecular Biology, FLENI, Montañeses, 2325, Ciudad Autónoma de Buenos Aires, Argentina.
Department of Psychiatry, Dell University of Texas at Austin and Institute of Early Life Adversity Research, Dell Medical School, The University of Texas, Austin, TX, 78712, USA.
Bellvitge Biomedical Research Institute-IDIBELL, Department of Psychiatry, Bellvitge University Hospital, Feixa Llarga S/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain; Network Center for Biomedical Research on Mental Health (CIBERSAM), Av. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029, Madrid, Spain; Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Carrer Fortuna, Edifici B, 08193, Bellaterra (Cerdanyola Del Vallès), Barcelona, Spain.

Prevention and early treatment strategies for Alzheimer's disease (AD) are hampered by the lack of research biomarkers. Neuropathological changes in the Locus Coeruleus (LC) are detected early in AD, and noradrenaline plays a neuroprotective role in LC projecting areas. We assessed functional connectivity (FC) of the brainstem in asymptomatic individuals at familial risk for AD hypothesizing that FC of the LC will be decreased in relation to not-at-risk individuals. Thirty-one offspring of patients with late-onset AD (O-LOAD) (22 females; mean age ± SD = 50.36 ± 8.32) and 28 healthy controls (HC) (20 females; mean age ± SD = 53.90 ± 8.44) underwent a neurocognitive evaluation and a resting-state functional magnetic resonance imaging acquisition. In FC analyses we evaluated whole-brain global connectivity of the brainstem area, and subsequently assessed seed-to-voxel FC patterns from regions showing between-group differences. O-LOAD individuals scored worse in neurocognitive measures of memory and overall functioning (pFDR<0.05). In imaging analyses, we observed that O-LOAD individuals showed decreased global connectivity in a cluster encompassing the left LC (peak = -4, -34, -32, pTFCE<0.05). Seed-to-voxel analyses revealed that this finding was largely explained by decreased connectivity between the LC and the cerebellar cortex. Moreover, FC between the LC and the left cerebellum correlated positively with delayed recall scores. FC between the LC and the cerebellar cortex is decreased in the healthy offspring of patients with LOAD, such connectivity measurements being associated with delayed memory scores. The assessment of FC between the LC and the cerebellum may serve as a biomarker of AD vulnerability.

中文翻译：

健康成年人中父母早老性痴呆病史的蓝斑功能中断。

缺乏研究生物标记物阻碍了阿尔茨海默氏病（AD）的预防和早期治疗策略。在AD早期就检测到了蓝斑轨迹（LC）的神经病理变化，去甲肾上腺素在LC投射区域起着神经保护作用。我们评估了无家族性AD风险的无症状个体脑干的功能连通性（FC），假设相对于非高危个体，LC的FC会降低。接受了迟发性AD（O-LOAD）患者的31例后代（22名女性;平均年龄±SD = 50.36±8.32）和28名健康对照（HC）（20名女性;平均年龄±SD = 53.90±8.44）神经认知评估和静止状态功能磁共振成像采集。在FC分析中，我们评估了脑干区域的全脑全局连通性，然后评估显示组间差异的区域的种子到体素FC模式。O-LOAD个体在记忆和整体功能的神经认知测量中得分较差（pFDR <0.05）。在成像分析中，我们观察到O-LOAD个体在包含左LC的簇中显示出全局连通性降低（峰值= -4，-34，-32，pTFCE <0.05）。种子到体素的分析表明，这一发现在很大程度上是由于LC和小脑皮层之间的连通性降低所致。此外，LC和左小脑之间的FC与延迟回忆得分呈正相关。在患有LOAD的患者的健康后代中，LC和小脑皮质之间的FC降低，这种连通性测量与延迟记忆评分相关。

更新日期：2020-01-31

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