Depressive symptoms and amyloid pathology
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 b...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 2025
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| In: |
JAMA psychiatry
Year: 2025, Volume: 82, Issue: 3, Pages: 296-310 |
| ISSN: | 2168-6238 |
| DOI: | 10.1001/jamapsychiatry.2024.4305 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1001/jamapsychiatry.2024.4305 Verlag, lizenzpflichtig, Volltext: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2829333 
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| Author Notes: | Wietse A. Wiels, MD; Julie E. Oomens, PhD; Sebastiaan Engelborghs, MD, PhD; Chris Baeken, MD, PhD; Christine A.F. von Arnim, PhD; Mercè Boada, MD, PhD; Mira Didic, PhD; Bruno Dubois, MD, PhD; Tormod Fladby, MD, PhD; Wiesje M. van der Flier, PhD; Giovanni B. Frisoni, MD; Lutz Fröhlich, MD, PhD; Kiran Dip Gill, PhD; Timo Grimmer, PhD; Helmut Hildebrandt, PhD; Jakub Hort, MD, PhD; Yoshiaki Itoh, PhD; Takeshi Iwatsubo, MD, PhD; Aleksandra Klimkowicz-Mrowiec, PhD; Dong Young Lee, MD, PhD; Alberto Lleó, MD, PhD; Pablo Martinez-Lage, PhD; Alexandre de Mendonça, MD, PhD; Philipp T. Meyer, MD, PhD; Elisabeth N. Kapaki, MD, PhD; Piero Parchi, PhD; Matteo Pardini, PhD; Lucilla Parnetti, MD, PhD; Julius Popp, MD; Lorena Rami, PhD; Eric M. Reiman, PhD; Juha O. Rinne, PhD; Karen M. Rodrigue, PhD; Pascual Sánchez-Juan, MD, PhD; Isabel Santana, MD, PhD; Marie Sarazin, MD, PhD; Nikolaos Scarmeas, MD, PhD; Ingmar Skoog, PhD; Peter J. Snyder, PhD; Reisa A. Sperling, PhD; Sylvia Villeneuve, PhD; Anders Wallin, MD, PhD; Jens Wiltfang, PhD; Henrik Zetterberg, MD, PhD; Rik Ossenkoppele, PhD; Frans R. J. Verhey, MD, PhD; Stephanie J. B. Vos, PhD; Pieter Jelle Visser, MD, PhD; Willemijn J. Jansen, PhD; and the Amyloid Biomarker Study group; for the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the A4 Study group, Dominantly Inherited Alzheimer Network (DIAN), European Prevention of Alzheimer’s Dementia (EPAD) consortium, Fundació ACE Healthy Brain Initiative (FACEHBI), Harvard Aging Brain Study (HABS), Japanese ADNI, Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE), Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT-AD) research group |
| Summary: | 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. |
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| Item Description: | Online veröffentlicht: 22. Januar 2025 Gesehen am 16.06.2025 |
| Physical Description: | Online Resource |
| ISSN: | 2168-6238 |
| DOI: | 10.1001/jamapsychiatry.2024.4305 |