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

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

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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