Depressive Symptoms and Amyloid Pathology

Wiels WA, Oomens JE, Engelborghs S, Baeken C, Von Arnim CA, Boada M, Didic M, Dubois B, Fladby T, Van Der Flier WM, Frisoni GB, Fröhlich L, Gill KD, Grimmer T, Hildebrandt H, Hort J, Itoh Y, Iwatsubo T, Klimkowicz-Mrowiec A, Lee DY, Lleó A, Martinez-Lage P, De Mendonça A, Meyer PT, Kapaki EN, Parchi P, Pardini M, Parnetti L, Popp J, Rami L, Reiman EM, Rinne JO, Rodrigue KM, Sánchez-Juan P, Santana I, Sarazin M, Scarmeas N, Skoog I, Snyder PJ, Sperling RA, Villeneuve S, Wallin A, Wiltfang J, Zetterberg H, Ossenkoppele R, Verhey FR, Vos SJ, Visser PJ, Jansen WJ, Alcolea D, Altomare D, Baiardi S, Baldeiras I, Bateman RJ, Blennow K, Bottlaender M, Den Braber A, Van Buchem MA, Byun MS, Cerman J, Chen K, Chipi E, Day GS, Drzezga A, Eckerström M, Ekblad LL, Epelbaum S, Förster S, Fortea J, Freund-Levi Y, Frings L, Guedj E, Hausner L, Hellwig S, Huey ED, Jiménez-Bonilla JF, Johnson KA, Juaristi AI, Kandimalla R, Paraskevas G, Kern S, Kirsebom BES, Kornhuber J, Lagarde J, Landau SM, Legdeur N, Llibre Guerra JJ, Maserejian NN, Marquié M, Minatani S, Morbelli SD, Mroczko B, Ntanasi E, De Oliveira CR, Olivieri P, Orellana A, Perrin RJ, Peters O, Prabhakar S, Ramakers IH, Rodríguez-Rodriguez E, Ruiz A, Rüther E, Selnes P, Silva D, Soininen H, Spiru L, Takeda A, Teichmann M, Tijms BM, Teunissen CE, Thompson LI, Vogelgsangs J, Vöglein J, Waldemar G, Wallin ÅK, Yannakoulia M, Yi D, Zettergren A (2025)

Publication Type: Journal article

Publication year: 2025

Journal

DOI: 10.1001/jamapsychiatry.2024.4305

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.

Authors with CRIS profile

Involved external institutions

Jagiellonian University Medical College Poland (PL) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Marqués de Valdecilla University Hospital / Hospital Universitario de Marqués de Valdecilla (HUMV) Spain (ES) Biomedical Research Networking Center on Neurodegenerative Diseases / Centro de Investigación Biomédica en Red Enfermedades neurodegenerativas (CIBERNED) Spain (ES) Postgraduate Institute of Medical Education and Research (PGIMER) / स्नातकोत्तर चिकित्सा शिक्षा एवं अनुसंधान संस्थान चण्डीगढ़ India (IN) Klinikum rechts der Isar Germany (DE) Carl von Ossietzky Universität Oldenburg Germany (DE) Motol University Hospital / Fakultní nemocnice v Motole Czech Republic (CZ) Vrije Universiteit Brussel (VUB) Belgium (BE) IRCCS Istituto delle Scienze Neurologiche di Bologna (ISNB) Italy (IT) Maastricht University Netherlands (NL) Universitätsklinikum Göttingen Germany (DE) Universitat Internacional de Catalunya Spain (ES) Hôpital de la Timone France (FR) Osaka Metropolitan University (OMU) Japan (JP) Assistance Publique-Hôpitaux de Paris (AP-HP) France (FR) Akershus University Hospital / Akershus universitetssykehus (Ahus) Norway (NO) Alzheimercentrum Amsterdam Netherlands (NL) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) Universitätsklinikum Mannheim Germany (DE) University of Genova / Università degli Studi di Genova Italy (IT) Università degli Studi di Perugia Italy (IT) CITA Alzheimer Foundation, Centre for Research and Advanced Therapies for Alzheimer's disease Spain (ES) University of Lisbon / Universidade de Lisboa (ULisboa) Portugal (PT) Universitätsklinikum Freiburg Germany (DE) Centre hospitalier Sainte-Anne France (FR) University of Zurich / Universität Zürich (UZH) Switzerland (CH) Eginition Hospital Greece (GR) Hospital Clínic de Barcelona Spain (ES) Harvard University United States (USA) (US) Banner Alzheimer's Institute United States (USA) (US) McConnell Brain Imaging Centre (BIC) Canada (CA) Turku University Hospital / Turun yliopistollinen keskussairaala (TYKS) Finland (FI) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) University of Texas at Dallas (UTD / UT Dallas) United States (USA) (US) Universidade de Coimbra Portugal (PT) Washington University in St. Louis United States (USA) (US) Università degli Studi di Brescia Italy (IT) University of Bologna / Università di Bologna Italy (IT) Université Paris-Saclay France (FR) University of Gothenburg / Göteborgs universitet Sweden (SE) Leiden University Medical Center Netherlands (NL) Mayo Clinic United States (USA) (US) Amsterdam Neuroscience Netherlands (NL) Universitätsklinikum Köln Germany (DE) Brown University United States (USA) (US) Klinikum der Universität München Germany (DE) Örebro University Sweden (SE) Rigshospitalet Denmark (DK) Lund University / Lunds universitet Sweden (SE) Aix-Marseille University / Aix-Marseille Université France (FR) Harokopio University / Χαροκόπειο Πανεπιστήμιο Greece (GR) Massachusetts General Hospital United States (USA) (US) Emory University United States (USA) (US) University Hospital of North Norway / Universitetssykehuset Nord-Norge (UNN) Norway (NO) University of California, Berkeley (UC Berkeley) United States (USA) (US) Biogen, Inc. United States (USA) (US) Medical University of Bialystok Poland (PL) CNC Center for Neuroscience and Cell Biology Portugal (PT) Charité - Universitätsmedizin Berlin Germany (DE) University of Eastern Finland Finland (FI) Carol Davila University of Medicine and Pharmacy / Universitatea de Medicină și Farmacie „Carol Davila” (UMF București) Romania (RO)

How to cite

APA:

Wiels, W.A., Oomens, J.E., Engelborghs, S., Baeken, C., Von Arnim, C.A., Boada, M.,... Zettergren, A. (2025). Depressive Symptoms and Amyloid Pathology. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2024.4305

MLA:

Wiels, Wietse A., et al. "Depressive Symptoms and Amyloid Pathology." JAMA Psychiatry (2025).

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