{ "abstract": "Objective: To evaluate the effects of exercise modality and weekly exercise dose on peripheral brain-derived neurotrophic factor (BDNF) and depressive symptoms in middle-aged and older adults with mild cognitive impairment (MCI), and to examine the robustness of the dose-specific predictions from the primary quadratic model across alternative dose–response functions. Methods: PubMed, Embase, Web of Science, the Cochrane Library, and APA PsycInfo were searched from inception to 13 April 2026. Randomized controlled trials involving adults aged 50 years or older with MCI and reporting BDNF or depression-related outcomes were included. Effect sizes were expressed as Hedges’ g. Separate Bayesian random-effects network dose–response meta-analyses were conducted for BDNF, overall depressive symptoms, and modality-specific depressive symptoms. The quadratic model was used as the primary model to predict intervention effects at different exercise doses. Linear, Emax, and natural cubic spline models were fitted as functional-form sensitivity analyses. Results: Twenty-eight studies involving 2,262 participants were included. In the primary quadratic analysis, the largest model-predicted effect on BDNF occurred at 440 MET-min/week (posterior mean, 0.752; 95% credible interval [CrI], 0.287 to 1.249), whereas the largest model-predicted effect on depressive symptoms occurred at 670 MET-min/week (posterior mean, 0.382; 95% CrI, 0.147 to 0.674). Dancing and multicomponent exercise showed comparatively favourable estimates at selected dose levels, whereas estimates for Tai Chi, walking, and yoga were less precise. Functional-form sensitivity analyses identified different dose locations for the maximum predicted effects. Therefore, 440 and 670 MET-min/week represent the maximum prediction points for BDNF and depressive symptoms, respectively, under the primary quadratic model, rather than established optimal exercise doses. Conclusion: Exercise interventions were associated with increased peripheral BDNF levels and improved depressive symptoms in middle-aged and older adults with MCI. The primary quadratic model predicted the largest effects at 440 MET-min/week for BDNF and 670 MET-min/week for depressive symptoms, suggesting a potentially non-linear dose–response relationship. Although these prediction points are important findings of the quadratic analysis, cross-model sensitivity indicates that they should be used to inform future dose-ranging research rather than be regarded as confirmed clinical optima.", "abstract_shown": true, "affiliations": [ "Hoseo University, Asan-si, Republic of Korea", "The College of Physical Education, Minnan Normal University, Zhangzhou, Fujian, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 3, "authors": [ { "affs": [ 0 ], "name": "Gong Cheng" }, { "affs": [ 1 ], "name": "Jinhui Qiu" }, { "name": "Shengtao Li" } ], "bibtex": "https://research.draconitic.com/paper/1bhyq69b3fd4q.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0358178", "fulltext_url": null, "id": "1bhyq69b3fd4q", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0358178", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2738|Dementia and Cognitive Impairment Research" ], [ "plos", "/Biology and life sciences/Neuroscience/Cognitive neuroscience/Cognitive neurology/Cognitive impairment" ], [ "plos", "/Biology and life sciences/Neuroscience/Cognitive science/Cognitive neuroscience/Cognitive neurology/Cognitive impairment" ], [ "plos", "/Biology and life sciences/Sports science/Sports and exercise medicine/Exercise" ], [ "plos", "/Engineering and technology/Electronics engineering/Electronics/Comparators" ], [ "plos", "/Medicine and health sciences/Mental health and psychiatry/Mood disorders/Depression" ], [ "plos", "/Medicine and health sciences/Neurology/Cognitive neurology/Cognitive impairment" ], [ "plos", "/Medicine and health sciences/Pharmaceutics/Dose prediction methods" ], [ "plos", "/Medicine and health sciences/Public and occupational health/Physical activity/Physical fitness/Exercise" ], [ "plos", "/Medicine and health sciences/Sports and exercise medicine/Exercise" ], [ "plos", "/People and places/Population groupings/Age groups/Adults/Elderly" ], [ "plos", "/Research and analysis methods/Database and informatics methods/Database searching" ], [ "plos", "/Science policy/Research integrity/Publication ethics" ] ], "openalex": "W7220861273", "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358178&type=printable", "pmcid": null, "pmid": null, "published": "2026-10-07", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/1bhyq69b3fd4q.ris", "sources": [ { "first_seen": "2026-10-30T12:17:30Z", "native_id": "10.1371/journal.pone.0358178", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0358178" } ], "subjects": [ { "field": "biology", "origin": "plos:cognitive neuroscience", "subfield": "neuroscience" }, { "field": "medicine", "origin": "plos:neurology", "subfield": "neurology" }, { "field": "medicine", "origin": "plos:mental health and psychiatry", "subfield": "psychiatry" } ], "title": "Dose- and modality-specific effects of exercise on BDNF and depression in middle-aged and older adults with mild cognitive impairment: A Bayesian network meta-analysis", "title_text": "Dose- and modality-specific effects of exercise on BDNF and depression in middle-aged and older adults with mild cognitive impairment: A Bayesian network meta-analysis", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:30Z", "url": "https://research.draconitic.com/paper/1bhyq69b3fd4q", "venue": "PLOS One", "versions": [] }