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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | JAMA Psychiatry |
| ISSN | 2168-622X |
| DOI | |
| Status | E-pub ahead of print - 2025 |
Bibliografisk note
Funding Information:Affiliations of The Amyloid Biomarker Study Group: Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Ramakers); Ace Alzheimer Center Barcelona \u2013 Universitat Internacional de Catalunya, Barcelona, Spain (Marqui\u00E9, Orellana, Ruiz); Centre for Biomedical Research Network on Neurodegenerative Diseases, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain (Alcolea, Fortea, Marqui\u00E9, Orellana, Ruiz); Department of Neurology, Institut de la M\u00E9moire et de la Maladie d\u2019Alzheimer, Centre de R\u00E9f\u00E9rence D\u00E9mences Rares, H\u00F4pital de la Piti\u00E9-Salp\u00EAtri\u00E8re, Assistance Publique\u2013 H\u00F4pitaux de Paris, Paris, France (Epelbaum, Teichmann); Department of Neurology, Alzheimer Centre Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers location Vrije Universiteit Medical Center, Amsterdam, Amsterdam, the Netherlands (den Braber, Legdeur, Tijms); Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (Hausner); Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic (Cerman); Department of Neurology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan (Minatani, Takeda); Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea (Byun); Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Alcolea, Fortea); Center for Research and Advanced Therapies, Cita-Alzheimer Foundation, Donostia-San Sebastian, Spain (Juaristi); Faculty of Medicine, University of Lisbon, Lisboa, Portugal (Silva); Department of Nuclear Medicine, Medical Center \u2013 University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany (Frings); National and Kapodistrian University of Athens, School of Medicine, 1st Department of Neurology, Eginition Hospital, Athens, Greece (Paraskevas); Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy (Baiardi); Centro Disturbi della Memoria, Laboratorio di Neurochimica Clinica, Clinica Neurologica, Universit\u00E0 di Perugia, Perugia, Italy (Chipi); Banner Alzheimer\u2019s Institute, Phoenix, Arizona (Chen); Turku Positron Emission Tomography Centre, University of Turku, Turku, Finland (Ekblad); Faculty of Medicine, University of Coimbra, Coimbra, Portugal (Baldeiras); Center for Neuroscience and Cell Biology, Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal (Baldeiras, de Oliveira); Neurology Department and Laboratory of Neurochemistry, Centro Hospitalar e Universit\u00E1rio de Coimbra, Coimbra, Portugal (Baldeiras); Department of Neurology of Memory and Language, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, H\u00F4pital Sainte Anne, Paris, France (Lagarde); Paris-Saclay University, BioMaps, Inserm, Commissariat \u00E0 l'\u00E9nergie atomique et aux \u00E9nergies alternatives, Service Hospitalier Frederic Joliot, Orsay, France (Bottlaender, Lagarde, Olivieri); Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, M\u00F6lndal, Sweden (Kern, Zettergren); Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00F6lndal, Sweden (Blennow); Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (Altomare); Department of Neurology and the Alzheimer\u2019s Disease Research Center, Washington University School of Medicine, St Louis, Missouri (Bateman, Llibre Guerra); Paris-Saclay University, Research Unit in Clinical and Translational Applicative NeuroImaging, Neurospin, Commissariat \u00E0 l'\u00E9nergie atomique et aux \u00E9nergies alternatives, Gif-sur-Yvette, France (Bottlaender); Department of Radiology, University Medical Center Leiden, Leiden, the Netherlands (van Buchem); Department of Neurology, Mayo Clinic in Florida, Jacksonville (Day); Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany (Drzezga); German Center for Neurodegenerative Diseases, Bonn-Cologne, Germany, (Drzezga); Institute of Neuroscience and Medicine, Molecular Organization of the Brain, Forschungszentrum J\u00FClich, J\u00FClich, Germany (Drzezga); Department of Psychology, University of Gothenburg, Gothenburg, Sweden (Eckerstr\u00F6m); Department of Geriatrics, Turku University Hospital, Wellbeing Services County of Southwestern Finland, Turku, Finland (Ekblad); Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany (F\u00F6rster); Department of Nuclear Medicine, Klinikum Bayreuth, Bayreuth, Germany (F\u00F6rster); School of Medical Sciences, \u00D6rebro University, \u00D6rebro, Sweden (Freund-Levi); Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet Center for Alzheimer Research, Stockholm, Sweden (Freund-Levi); Department of Old Age Psychiatry, Psychology and Neuroscience, King\u2019s College, London, United Kingdom (Freund-Levi); Aix Marseille University, L\u2019Assistance publique\u2013H\u00F4pitaux de Marseille, Centre National de la Recherche Scientifique, Centrale Marseille, Institut Fresnel, Timone Hospital, Centre Europ\u00E9en de Recherche en Imagerie M\u00E9dicale, Nuclear Medicine Department, Marseille, France (Guedj); Department of Psychiatry and Psychotherapy Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (Hellwig); Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island (Huey); Department of Nuclear Medicine, Marqu\u00E9s de Valdecilla University Hospital and Instituto de Investigaci\u00F3n Marqu\u00E9s de Valdecilla, Santander, Spain (Jim\u00E9nez-Bonilla); Department of Radiology, Massachusetts General Hospital, Boston (Johnson); Department of Radiation Oncology, Emory University, Atlanta, Georgia (Kandimalla); Applied Biology, Council of Scientific and Industrial Research\u2013Indian Institute of Chemical Technology, Hyderabad, Telangana State, India (Kandimalla); Department of Biochemistry, Kakatiya Medical College/Mahatma Gandhi Memorial Hospital, Warangal, Telangana State, India (Kandimalla); Department of Psychiatry, Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, V\u00E4stra G\u00F6talandsregion, Sweden (Kern); Department of Neurology, University Hospital of North Norway, Troms\u00F8, Norway (Kirsebom); Department of Psychology, The Arctic University of Norway, Troms\u00F8, Norway (Kirsebom); Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany (Kornhuber); Helen Wills Neuroscience Institute, University of California, Berkeley (Landau); Department of Epidemiology, Biogen, Cambridge, Massachusetts (Maserejian); Department of Health Sciences, University of Genoa, Genoa, Italy (Morbelli); Ospedale Policlinico San Martino, Scientific Institute for Research, Hospitalization and Healthcare, Genoa, Italy (Morbelli); Department of Neurodegeneration Diagnostics, Medical University of Bia\u0142ystok, Bia\u0142ystok, Poland (Mroczko); Department of Biochemical Diagnostics, University Hospital of Bia\u0142ystok, Bia\u0142ystok, Poland (Mroczko); Department of Nutrition and Diatetics, Harokopio University, Kallithea, Athens, Greece (Ntanasi, Yannakoulia); Department of Pathology and Immunology, Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri (Perrin); Charit\u00E9 Universit\u00E4tsmedizin Berlin\u2013Campus Benjamin Franklin, Berlin, Deutschland (Peters); Department of Neurology, Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh, India (Prabhakar); Neurology Department, Hospital Universitario Marqu\u00E9s de Valdecilla and Instituto de Investigaci\u00F3n Sanitaria Valdecilla, University of Cantabria, Santander, Biomedical Research Networking Center on Neurodegenerative Diseases, Madrid, Santander, Spain (Rodr\u00EDguez-Rodriguez); Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, G\u00F6ttingen, Germany (R\u00FCther); Department of Neurology, Akershus University Hospital, Lorenskog, Norway (Selnes); Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland (Soininen); Neurocenter, Department of Neurology, Kuopio University Hospital, Kuopio, Finland (Soininen); Geriatrics, Gerontology and Old Age Psychiatry Clinical Department, Carol Davila University of Medicine and Pharmacy-Elias, Emergency Clinical Hospital, Bucharest, Romania (Spiru); Excellence Center for Memory Diseases, Brain Health and Longevity Medicine, Ana Aslan International Foundation, Bucharest, Romania (Spiru); Neurochemistry Lab, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam University Medical Centers location Vrije Universiteit Medical Center, Amsterdam, the Netherlands (Teunissen); Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island (Thompson); Translational Neuroscience Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts (Vogelgsangs); Department of Neurology, University Hospital of Munich, Munich, Germany (V\u00F6glein); German Center for Neurodegenerative Diseases, Munich, Germany (V\u00F6glein); Munich Cluster for Systems Neurology, Munich, Germany (V\u00F6glein); Danish Dementia Research Center, Department of Neurology, Copenhagen University Hospital\u2013Rigshospitalet, Copenhagen, Denmark (Waldemar); Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark (Waldemar); Cognitive Disorder Research Unit, Department of Clinical Sciences, Malm\u00F6, Sweden (Wallin); Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea (Yi).
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