Lifestyle intervention and cognitive outcomes in Down syndrome: a horizon 21 European Down syndrome consortium scoping review
Year: 2026
Type: article
Study design: Systematic Review
Abstract: BACKGROUND: Life expectancy for individuals with Down syndrome (DS) has significantly increased, primarily due to medical advances. While DS is considered a genetically determined form of Alzheimer’s disease (DS-AD), with neuropathological markers evident by age 40, the onset of clinical dementia varies. Modifiable risk factors are thought to contribute meaningfully to dementia risk in the general population. Advances in intervention studies in the general population suggest cognitive decline can be reduced through multimodal lifestyle interventions, however no large-scale multimodal studies have been conducted in the DS population. SEARCH STRATEGY: A comprehensive search was conducted across five electronic databases—Medline, EMBASE, CINAHL, Web of Science, and ASSIA to identify studies that examined the relationship between lifestyle interventions and cognitive outcomes in adults with DS. The search combined database-specific controlled language with keywords related to exercise, diet, social activities, cardiovascular health, and brain stimulation. Studies included were peer-reviewed original research articles focusing on adults with DS and reported on cognitive outcomes or AD-related biomarkers. RESULTS: The search yielded 24,774 articles, with 16,868 remaining after duplicates were removed. A total of 44 articles met inclusion criteria across the domains of exercise, diet, cardiovascular health, social connectedness, and cognitive stimulation. Most studies focused on exercise, indicating some cognitive benefits, particularly in executive functions and working memory, though results were inconsistent, and many suggested the necessity of high adherence to intervention protocols. No studies were found that examined the direct impact of diet on cognition in DS. Findings on cognitive stimulation, cardiovascular health and social connectedness suggested potential but inconclusive benefits for cognitive function. CONCLUSIONS: This review underscores the significant gaps in research regarding non-pharmacological interventions for DS-AD. It highlights the need for tailored, well-structured studies to better understand and leverage potential cognitive benefits of lifestyle interventions in the DS population. Implementing such interventions early in life and before significant disease progression may help maintain quality of life and independence among individuals with DS. Future research should focus on comprehensive, multi-domain interventions to ascertain their efficacy and optimal application.
Authors: Eimear McGlinchey, Sarah Pape, Shahid H. Zaman, Jessica Eustace-Cook, Anna Stockbauer, Eleni Baldimtsi, Ellen Melbye Langballe, Frode Kibsgaard Larsen, Katja Sandkühler, Phoebe Ivain, Anne-Sophie Rebillat, Pierre Ecrement, Mary McCarron, Bessy Benejam, Wan Ming Khoo, Juan Fortea, Johannes Levin, Fredrik Öhman, Ann-Charlotte Granholm-Bentley, Andre Strydom, Georg Nübling
Institutions: University of California, San Francisco, Trinity College Dublin, Global Brain Health Institute, King's College London, University of Cambridge, German Center for Neurodegenerative Diseases, Ludwig-Maximilians-Universität München, Aristotle University of Thessaloniki, Oslo University Hospital, Sykehuset i Vestfold, Norwegian National Centre for Ageing and Health, University of Oslo, Fondation Jérôme-Lejeune, Universitat Autònoma de Barcelona, Hospital de Sant Pau, Biomedical Research Networking Center on Neurodegenerative Diseases, Institut de Recerca Sant Pau, Munich Cluster for Systems Neurology, University of Gothenburg, Medical University of South Carolina
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,990
Funders: Health Research Board, Global Brain Health Institute, Alzheimer's Society, National Institute for Health and Care Research, European Commission, Generalitat de Catalunya, Else Kröner-Fresenius-Stiftung, Fundación Tatiana Pérez de Guzmán el Bueno, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, National Institutes of Health, Horizon 2020 Framework Programme, Medical Research Council, NIHR Cambridge Biomedical Research Centre, National Institute on Aging
Awards: G1055184294, G1178615512, DS-ARC: A Remote Digital Cognitive Assessment for Down Syndrome-Associated Alzheimer's Disease, G1637266829, G1783860944, G1838929904, The Role of Inflammation and NGF Dysfunction in the Evolution of AlzheimerDisease Pathology in Down syndrome, Clinical trials to prevent Alzheimer's Disease in Down Syndrome, G2493601830, G2537968379, G2940840415, G3012247180, G3342877126, Neuropathological and amyloid peptide differences between DS and familial AD with duplications and missense mutations in APP gene, G4753630297, G477375770, LonDownsPREVENT: A longitudinal study of the mechanisms of cerebral amyloid angiopathy and neurodegeneration in Down syndrome to inform AD prevention, G6049260834, G6194374829, G6283029999, G6555716666, G7069699392, JPND The locus coeruleus: at the crossroad of dementia syndromes, G9000024916, G9000093583, G9000159375, G9000212820, G9000292890, G968800864
OpenAlex ID: W7155063017