% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Wiels:277426, author = {Wiels, Wietse A and Oomens, Julie E and Engelborghs, Sebastiaan and Baeken, Chris and von Arnim, Christine A F and Boada, Mercè and Didic, Mira and Dubois, Bruno and Fladby, Tormod and van der Flier, Wiesje M and Frisoni, Giovanni B and Fröhlich, Lutz and Gill, Kiran Dip and Grimmer, Timo and Hildebrandt, Helmut and Hort, Jakub and Itoh, Yoshiaki and Iwatsubo, Takeshi and Klimkowicz-Mrowiec, Aleksandra and Lee, Dong Young and Lleó, Alberto and Martinez-Lage, Pablo and de Mendonça, Alexandre and Meyer, Philipp T and Kapaki, Elisabeth N and Parchi, Piero and Pardini, Matteo and Parnetti, Lucilla and Popp, Julius and Rami, Lorena and Reiman, Eric M and Rinne, Juha O and Rodrigue, Karen M and Sánchez-Juan, Pascual and Santana, Isabel and Sarazin, Marie and Scarmeas, Nikolaos and Skoog, Ingmar and Snyder, Peter J and Sperling, Reisa A and Villeneuve, Sylvia and Wallin, Anders and Wiltfang, Jens and Zetterberg, Henrik and Ossenkoppele, Rik and Verhey, Frans R J and Vos, Stephanie J B and Visser, Pieter Jelle and Jansen, Willemijn J and Alcolea, Daniel and Altomare, Daniele and Baiardi, Simone and Baldeiras, Ines and Bateman, Randall J and Blennow, Kaj and Bottlaender, Michel and den Braber, Anouk and van Buchem, Mark A and Byun, Min Soo and Cerman, Jirí and Chen, Kewei and Chipi, Elena and Day, Gregory S and Drzezga, Alexander and Eckerström, Marie and Ekblad, Laura L and Epelbaum, Stéphane and Förster, Stefan and Fortea, Juan and Freund-Levi, Yvonne and Frings, Lars and Guedj, Eric and Hausner, Lucrezia and Hellwig, Sabine and Huey, Edward D and Jiménez-Bonilla, Julio F and Johnson, Keith A and Juaristi, Ane Iriondo and Kandimalla, Ramesh and Paraskevas, George and Kern, Silke and Kirsebom, Bjørn-Eivind S and Kornhuber, Johannes and Lagarde, Julien and Landau, Susan M and Legdeur, Nienke and Llibre Guerra, Jorge J and Maserejian, Nancy N and Marquié, Marta and Minatani, Shinobu and Morbelli, Silvia Daniela and Mroczko, Barbara and Ntanasi, Eva and de Oliveira, Catarina Resende and Olivieri, Pauline and Orellana, Adelina and Perrin, Richard J and Peters, Oliver and Prabhakar, Sudesh and Ramakers, Inez H and Rodríguez-Rodriguez, Eloy and Ruiz, Agustín and Rüther, Eckart and Selnes, Per and Silva, Dina and Soininen, Hilkka and Spiru, Luiza and Takeda, Akitoshi and Teichmann, Marc and Tijms, Betty M and Teunissen, Charlotte E and Thompson, Loisa I and Vogelgsangs, Jonathan and Vöglein, Jonathan and Waldemar, Gunhild and Wallin, Åsa K and Yannakoulia, Mary and Yi, Dahyun and Zettergren, Anna}, collaboration = {group, Amyloid Biomarker Study and Initiative, Alzheimer’s Disease Neuroimaging}, title = {{D}epressive {S}ymptoms and {A}myloid {P}athology.}, journal = {JAMA psychiatry}, volume = {82}, number = {3}, issn = {2168-622X}, address = {Chicago, Ill.}, publisher = {AMA}, reportid = {DZNE-2025-00409}, pages = {296 - 310}, year = {2025}, abstract = {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.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.}, keywords = {Humans / Female / Male / Aged / Depression / Middle Aged / Cross-Sectional Studies / Cognitive Dysfunction / Amyloid beta-Peptides: cerebrospinal fluid / Amyloid beta-Peptides: metabolism / Positron-Emission Tomography / Aged, 80 and over / Adult / Biomarkers: cerebrospinal fluid / Peptide Fragments: cerebrospinal fluid / Apolipoprotein E4: genetics / Age Factors / Amyloid beta-Peptides (NLM Chemicals) / Biomarkers (NLM Chemicals) / Peptide Fragments (NLM Chemicals) / amyloid beta-protein (1-42) (NLM Chemicals) / Apolipoprotein E4 (NLM Chemicals)}, cin = {AG Boecker / Clinical Research (Munich)}, ddc = {610}, cid = {I:(DE-2719)1011202 / I:(DE-2719)1111015}, pnm = {353 - Clinical and Health Care Research (POF4-353)}, pid = {G:(DE-HGF)POF4-353}, experiment = {EXP:(DE-2719)DIAN-20090101}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:39841452}, pmc = {pmc:PMC11883504}, doi = {10.1001/jamapsychiatry.2024.4305}, url = {https://pub.dzne.de/record/277426}, }