Wiels Wietse A, Oomens Julie E, Engelborghs Sebastiaan, Baeken Chris, von Arnim Christine A F, Boada Mercè, Didic Mira, Dubois Bruno, Fladby Tormod, van der Flier Wiesje M, Frisoni Giovanni B, Fröhlich Lutz, Gill Kiran Dip, Grimmer Timo, Hildebrandt Helmut, Hort Jakub, Itoh Yoshiaki, Iwatsubo Takeshi, Klimkowicz-Mrowiec Aleksandra, Lee Dong Young, Lleó Alberto, Martinez-Lage Pablo, de Mendonça Alexandre, Meyer Philipp T, Kapaki Elisabeth N, Parchi Piero, Pardini Matteo, Parnetti Lucilla, Popp Julius, Rami Lorena, Reiman Eric M, Rinne Juha O, Rodrigue Karen M, Sánchez-Juan Pascual, Santana Isabel, Sarazin Marie, Scarmeas Nikolaos, Skoog Ingmar, Snyder Peter J, Sperling Reisa A, Villeneuve Sylvia, Wallin Anders, Wiltfang Jens, Zetterberg Henrik, Ossenkoppele Rik, Verhey Frans R J, Vos Stephanie J B, Visser Pieter Jelle, Jansen Willemijn J, Alcolea Daniel, Altomare Daniele, Baiardi Simone, Baldeiras Ines, Bateman Randall J, Blennow Kaj, Bottlaender Michel, den Braber Anouk, van Buchem Mark A, Byun Min Soo, Cerman Jirí, Chen Kewei, Chipi Elena, Day Gregory S, Drzezga Alexander, Eckerström Marie, Ekblad Laura L, Epelbaum Stéphane, Förster Stefan, Fortea Juan, Freund-Levi Yvonne, Frings Lars, Guedj Eric, Hausner Lucrezia, Hellwig Sabine, Huey Edward D, Jiménez-Bonilla Julio F, Johnson Keith A, Juaristi Ane Iriondo, Kandimalla Ramesh, Paraskevas George, Kern Silke, Kirsebom Bjørn-Eivind S, Kornhuber Johannes, Lagarde Julien, Landau Susan M, Legdeur Nienke, Llibre Guerra Jorge J, Maserejian Nancy N, Marquié Marta, Minatani Shinobu, Morbelli Silvia Daniela, Mroczko Barbara, Ntanasi Eva, de Oliveira Catarina Resende, Olivieri Pauline, Orellana Adelina, Perrin Richard J, Peters Oliver, Prabhakar Sudesh, Ramakers Inez H, Rodríguez-Rodriguez Eloy, Ruiz Agustín, Rüther Eckart, Selnes Per, Silva Dina, Soininen Hilkka, Spiru Luiza, Takeda Akitoshi, Teichmann Marc, Tijms Betty M, Teunissen Charlotte E, Thompson Loisa I, Vogelgsangs Jonathan, Vöglein Jonathan, Waldemar Gunhild, Wallin Åsa K, Yannakoulia Mary, Yi Dahyun, Zettergren Anna
Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Department of Neurology, Onze-Lieve-Vrouw Hospital, Aalst, Belgium.
JAMA Psychiatry. 2025 Mar 1;82(3):296-310. doi: 10.1001/jamapsychiatry.2024.4305.
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.
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.
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.
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.
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.
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工作。这项大规模研究旨在阐明抑郁症状与淀粉样蛋白病理之间的关联。
研究无痴呆症老年人中抑郁症状与淀粉样蛋白病理之间的关联及其对年龄、性别、教育程度和载脂蛋白E（APOE）基因型的依赖性。
设计、背景和参与者：使用来自淀粉样蛋白生物标志物研究数据汇总计划的数据进行横断面分析。汇总并统一了来自49项基于人群的研究、基于研究和记忆诊所研究的数据。淀粉样蛋白生物标志物研究自2012年以来一直在收集数据，目前仍在进行数据收集。在分析时，淀粉样蛋白生物标志物研究纳入了95个中心。该研究包括9746名认知正常（NC）的个体和3023名年龄在34至100岁之间的轻度认知障碍（MCI）参与者，这些参与者有淀粉样蛋白生物标志物、抑郁症状和年龄的数据。数据于2022年12月至2024年2月进行分析。
脑脊液中β淀粉样蛋白1-42水平或淀粉样蛋白正电子发射断层扫描用于确定是否存在淀粉样蛋白病理。抑郁症状的存在根据经过验证的抑郁评定量表评分、当前抑郁症临床诊断的证据或自我报告的抑郁症状来确定。
在认知正常的个体（平均[标准差]年龄，68.6[8.9]岁；5664名[58.2%]为女性；3002名[34.0%]为APOE ε4携带者；937名[9.6%]有抑郁症状；2648名[27.2%]有淀粉样蛋白病理）中，抑郁症状的存在与淀粉样蛋白病理无关（比值比[OR]，1.13；95%置信区间，0.90-1.40；P = 0.29）。在轻度认知障碍个体（平均[标准差]年龄，70.2[8.7]岁；1481名[49.0%]为女性；1046名[44.8%]为APOE ε4携带者；824名[27.3%]有抑郁症状；1668名[55.8%]有淀粉样蛋白病理）中，抑郁症状的存在与淀粉样蛋白病理的可能性较低有关（OR，0.73；95%置信区间0.61-0.89；P = 0.001）。考虑亚组效应时，在认知正常的个体中，抑郁症状的存在与APOE ε4非携带者中淀粉样蛋白病理的频率较高有关（平均差异，5.0%；95%置信区间1.0-9.0；P = 0.02），但在APOE ε4携带者中并非如此。在轻度认知障碍个体中情况并非如此。
抑郁症状与认知正常参与者中淀粉样蛋白病理的较高频率并非始终相关，而与轻度认知障碍参与者中淀粉样蛋白病理的可能性较低有关。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。
