000277426 001__ 277426 000277426 005__ 20250323000946.0 000277426 0247_ $$2doi$$a10.1001/jamapsychiatry.2024.4305 000277426 0247_ $$2pmid$$apmid:39841452 000277426 0247_ $$2pmc$$apmc:PMC11883504 000277426 0247_ $$2ISSN$$a2168-622X 000277426 0247_ $$2ISSN$$a0003-990X 000277426 0247_ $$2ISSN$$a0375-8532 000277426 0247_ $$2ISSN$$a1538-3636 000277426 0247_ $$2ISSN$$a2168-6238 000277426 0247_ $$2ISSN$$a2330-9636 000277426 0247_ $$2altmetric$$aaltmetric:173257015 000277426 037__ $$aDZNE-2025-00409 000277426 041__ $$aEnglish 000277426 082__ $$a610 000277426 1001_ $$aWiels, Wietse A$$b0 000277426 245__ $$aDepressive Symptoms and Amyloid Pathology. 000277426 260__ $$aChicago, Ill.$$bAMA$$c2025 000277426 3367_ $$2DRIVER$$aarticle 000277426 3367_ $$2DataCite$$aOutput Types/Journal article 000277426 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1742377671_22879 000277426 3367_ $$2BibTeX$$aARTICLE 000277426 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000277426 3367_ $$00$$2EndNote$$aJournal Article 000277426 520__ $$aDepressive 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. 000277426 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0 000277426 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000277426 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides 000277426 650_7 $$2NLM Chemicals$$aBiomarkers 000277426 650_7 $$2NLM Chemicals$$aPeptide Fragments 000277426 650_7 $$2NLM Chemicals$$aamyloid beta-protein (1-42) 000277426 650_7 $$2NLM Chemicals$$aApolipoprotein E4 000277426 650_2 $$2MeSH$$aHumans 000277426 650_2 $$2MeSH$$aFemale 000277426 650_2 $$2MeSH$$aMale 000277426 650_2 $$2MeSH$$aAged 000277426 650_2 $$2MeSH$$aDepression 000277426 650_2 $$2MeSH$$aMiddle Aged 000277426 650_2 $$2MeSH$$aCross-Sectional Studies 000277426 650_2 $$2MeSH$$aCognitive Dysfunction 000277426 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid 000277426 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism 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