Depressive Symptoms and Amyloid Pathology.

IF 22.5 1区医学 Q1 PSYCHIATRY

JAMA Psychiatry Pub Date : 2025-01-22 DOI:10.1001/jamapsychiatry.2024.4305

Wietse A Wiels, Julie E Oomens, Sebastiaan Engelborghs, Chris Baeken, Christine A F von Arnim, Mercè Boada, Mira Didic, Bruno Dubois, Tormod Fladby, Wiesje M van der Flier, Giovanni B Frisoni, Lutz Fröhlich, Kiran Dip Gill, Timo Grimmer, Helmut Hildebrandt, Jakub Hort, Yoshiaki Itoh, Takeshi Iwatsubo, Aleksandra Klimkowicz-Mrowiec, Dong Young Lee, Alberto Lleó, Pablo Martinez-Lage, Alexandre de Mendonça, Philipp T Meyer, Elisabeth N Kapaki, Piero Parchi, Matteo Pardini, Lucilla Parnetti, Julius Popp, Lorena Rami, Eric M Reiman, Juha O Rinne, Karen M Rodrigue, Pascual Sánchez-Juan, Isabel Santana, Marie Sarazin, Nikolaos Scarmeas, Ingmar Skoog, Peter J Snyder, Reisa A Sperling, Sylvia Villeneuve, Anders Wallin, Jens Wiltfang, Henrik Zetterberg, Rik Ossenkoppele, Frans R J Verhey, Stephanie J B Vos, Pieter Jelle Visser, Willemijn J Jansen, Daniel Alcolea, Daniele Altomare, Simone Baiardi, Ines Baldeiras, Randall J Bateman, Kaj Blennow, Michel Bottlaender, Anouk den Braber, Mark A van Buchem, Min Soo Byun, Jirí Cerman, Kewei Chen, Elena Chipi, Gregory S Day, Alexander Drzezga, Marie Eckerström, Laura L Ekblad, Stéphane Epelbaum, Stefan Förster, Juan Fortea, Yvonne Freund-Levi, Lars Frings, Eric Guedj, Lucrezia Hausner, Sabine Hellwig, Edward D Huey, Julio F Jiménez-Bonilla, Keith A Johnson, Ane Iriondo Juaristi, Ramesh Kandimalla, George Paraskevas, Silke Kern, Bjørn-Eivind S Kirsebom, Johannes Kornhuber, Julien Lagarde, Susan M Landau, Nienke Legdeur, Jorge J Llibre Guerra, Nancy N Maserejian, Marta Marquié, Shinobu Minatani, Silvia Daniela Morbelli, Barbara Mroczko, Eva Ntanasi, Catarina Resende de Oliveira, Pauline Olivieri, Adelina Orellana, Richard J Perrin, Oliver Peters, Sudesh Prabhakar, Inez H Ramakers, Eloy Rodríguez-Rodriguez, Agustín Ruiz, Eckart Rüther, Per Selnes, Dina Silva, Hilkka Soininen, Luiza Spiru, Akitoshi Takeda, Marc Teichmann, Betty M Tijms, Charlotte E Teunissen, Loisa I Thompson, Jonathan Vogelgsangs, Jonathan Vöglein, Gunhild Waldemar, Åsa K Wallin, Mary Yannakoulia, Dahyun Yi, Anna Zettergren

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The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024.Main outcomes and measures: Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms.Results: In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI.Conclusions and relevance: Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. 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引用次数: 0

Abstract

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Objective: To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia.

Design, setting, and participants: Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024.

Main outcomes and measures: Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms.

Results: In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI.

Conclusions and relevance: Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

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抑郁症状与淀粉样蛋白病理

重要性：抑郁症状与老年人认知能力下降有关。潜在机制的不确定性阻碍了诊断和治疗的努力。这项大规模的研究旨在阐明抑郁症状与淀粉样蛋白病理之间的关系。目的：探讨老年痴呆患者抑郁症状与淀粉样蛋白病理的关系及其与年龄、性别、教育程度和APOE基因型的关系。设计、设置和参与者：使用淀粉样蛋白生物标志物研究数据池计划的数据进行横断面分析。来自49项研究、基于人群的研究和记忆临床研究的数据被汇总和协调。淀粉样蛋白生物标志物研究自2012年以来一直在收集数据，数据收集仍在进行中。在分析时，95个中心被纳入淀粉样蛋白生物标志物研究。该研究包括9746名正常认知（NC）个体和3023名轻度认知障碍（MCI）参与者，年龄在34至100岁之间，他们的淀粉样蛋白生物标志物、抑郁症状的存在和年龄均可获得。数据分析时间为2022年12月至2024年2月。主要结果和测量：脑脊液中淀粉样蛋白β1-42水平或淀粉样蛋白正电子发射断层扫描用于确定淀粉样蛋白病理的存在或不存在。抑郁症状的存在是根据有效的抑郁评定量表得分、当前临床诊断抑郁的证据或自我报告的抑郁症状来确定的。结果：NC患者的平均[SD]年龄为68.6[8.9]岁；女性5664人[58.2%]；3002个[34.0%]APOE ε4携带者；有抑郁症状937例（9.6%）；2648例（27.2%）有淀粉样蛋白病理)，抑郁症状的存在与淀粉样蛋白病理无关(优势比[OR]， 1.13；95% ci, 0.90-1.40；p = .29)。轻度认知障碍患者的平均[SD]年龄为70.2[8.7]岁；女性1481人[49.0%]；APOE ε4携带者1046例[44.8%]；824人（27.3%）有抑郁症状；1668例[55.8%]有淀粉样蛋白病理)，抑郁症状的存在与淀粉样蛋白病理的可能性较低相关(OR, 0.73；95% ci 0.61-0.89；p = .001)。当考虑亚组效应时，在NC个体中，抑郁症状的存在与APOE ε4非携带者淀粉样蛋白病理的较高频率相关(平均差异为5.0%；95% ci 1.0-9.0；P = .02)，但APOE ε4携带者无明显差异。这与轻度认知障碍患者的情况不同。结论和相关性：抑郁症状与NC患者淀粉样蛋白病理的高频率并不一致相关，而与MCI患者淀粉样蛋白病理的低可能性相关。这些发现不受年龄、性别或教育水平的影响。淀粉样蛋白积累以外的机制可能通常是晚年抑郁症状的基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JAMA Psychiatry PSYCHIATRY-

CiteScore

30.60

自引率

1.90%

发文量

233

期刊介绍： JAMA Psychiatry is a global, peer-reviewed journal catering to clinicians, scholars, and research scientists in psychiatry, mental health, behavioral science, and related fields. The Archives of Neurology & Psychiatry originated in 1919, splitting into two journals in 1959: Archives of Neurology and Archives of General Psychiatry. In 2013, these evolved into JAMA Neurology and JAMA Psychiatry, respectively. JAMA Psychiatry is affiliated with the JAMA Network, a group of peer-reviewed medical and specialty publications.