Optimizing midlife metabolic syndrome thresholds for dementia: a prospective study of two UK population-based cohorts
Abstract Background The concept of metabolic syndrome (MetS) was developed to identify individuals at higher risk of type 2 diabetes and cardiovascular disease, but its relevance for dementia remains unclear. We examined MetS in midlife for association with late-onset dementia, focusing on the thres...
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BMC
2025-04-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-025-01732-8 |
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| author | Sam Vidil Archana Singh-Manoux Benjamin Landré Aurore Fayosse Séverine Sabia Marcos D. Machado-Fragua |
| author_facet | Sam Vidil Archana Singh-Manoux Benjamin Landré Aurore Fayosse Séverine Sabia Marcos D. Machado-Fragua |
| author_sort | Sam Vidil |
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| description | Abstract Background The concept of metabolic syndrome (MetS) was developed to identify individuals at higher risk of type 2 diabetes and cardiovascular disease, but its relevance for dementia remains unclear. We examined MetS in midlife for association with late-onset dementia, focusing on the thresholds of MetS components that carry risk for dementia. Methods MetS components (waist circumference, blood pressure, triglycerides, HDL-C, and fasting glucose) were measured on 6,137 white participants < 60 years from the Whitehall II (WII) cohort study. A changepoint method in time-to-event analyses was used to identify optimal thresholds, and those exhibiting better performance for dementia were retained to develop a revised MetS definition. Results were validated on 171,886 participants in the UK Biobank (UKB) study. Results Over a median follow-up of 22.6 years in WII and 13.8 years in UKB, 522 and 418 late-onset dementia cases were recorded, respectively. Optimized thresholds for triglycerides and fasting glucose performed better than original MetS thresholds in WII, and were used to develop a revised MetS definition. The MetS scale had a linear association with dementia, and 1-component increment (range 0 to 5) was associated with higher dementia risk using the revised MetS definition (HR, 95% CI: 1.11, 1.03–1.19) but not the original MetS definition (HR, 95% CI: 1.06, 0.98–1.14) in WII. In UKB, the revised MetS definition exhibited better performance for dementia risk than the original definition (p for HR comparison < 0.01). Conclusions MetS in midlife is potentially an important target for dementia prevention. However, the thresholds for triglycerides and glucose that carry risk need to be tailored specifically for dementia. |
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| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-1b7b2b767f9c4592b69f7a3b56c4cb8d2025-08-20T02:30:22ZengBMCAlzheimer’s Research & Therapy1758-91932025-04-0117111110.1186/s13195-025-01732-8Optimizing midlife metabolic syndrome thresholds for dementia: a prospective study of two UK population-based cohortsSam Vidil0Archana Singh-Manoux1Benjamin Landré2Aurore Fayosse3Séverine Sabia4Marcos D. Machado-Fragua5Epidemiology of Ageing and Neurodegenerative diseases (EpiAgeing), Université Paris Cité, Inserm U1153Epidemiology of Ageing and Neurodegenerative diseases (EpiAgeing), Université Paris Cité, Inserm U1153Epidemiology of Ageing and Neurodegenerative diseases (EpiAgeing), Université Paris Cité, Inserm U1153Epidemiology of Ageing and Neurodegenerative diseases (EpiAgeing), Université Paris Cité, Inserm U1153Epidemiology of Ageing and Neurodegenerative diseases (EpiAgeing), Université Paris Cité, Inserm U1153Epidemiology of Ageing and Neurodegenerative diseases (EpiAgeing), Université Paris Cité, Inserm U1153Abstract Background The concept of metabolic syndrome (MetS) was developed to identify individuals at higher risk of type 2 diabetes and cardiovascular disease, but its relevance for dementia remains unclear. We examined MetS in midlife for association with late-onset dementia, focusing on the thresholds of MetS components that carry risk for dementia. Methods MetS components (waist circumference, blood pressure, triglycerides, HDL-C, and fasting glucose) were measured on 6,137 white participants < 60 years from the Whitehall II (WII) cohort study. A changepoint method in time-to-event analyses was used to identify optimal thresholds, and those exhibiting better performance for dementia were retained to develop a revised MetS definition. Results were validated on 171,886 participants in the UK Biobank (UKB) study. Results Over a median follow-up of 22.6 years in WII and 13.8 years in UKB, 522 and 418 late-onset dementia cases were recorded, respectively. Optimized thresholds for triglycerides and fasting glucose performed better than original MetS thresholds in WII, and were used to develop a revised MetS definition. The MetS scale had a linear association with dementia, and 1-component increment (range 0 to 5) was associated with higher dementia risk using the revised MetS definition (HR, 95% CI: 1.11, 1.03–1.19) but not the original MetS definition (HR, 95% CI: 1.06, 0.98–1.14) in WII. In UKB, the revised MetS definition exhibited better performance for dementia risk than the original definition (p for HR comparison < 0.01). Conclusions MetS in midlife is potentially an important target for dementia prevention. However, the thresholds for triglycerides and glucose that carry risk need to be tailored specifically for dementia.https://doi.org/10.1186/s13195-025-01732-8Cardiometabolic risk factorsMetabolic syndromeOptimal thresholdsDementiaMidlife |
| spellingShingle | Sam Vidil Archana Singh-Manoux Benjamin Landré Aurore Fayosse Séverine Sabia Marcos D. Machado-Fragua Optimizing midlife metabolic syndrome thresholds for dementia: a prospective study of two UK population-based cohorts Alzheimer’s Research & Therapy Cardiometabolic risk factors Metabolic syndrome Optimal thresholds Dementia Midlife |
| title | Optimizing midlife metabolic syndrome thresholds for dementia: a prospective study of two UK population-based cohorts |
| title_full | Optimizing midlife metabolic syndrome thresholds for dementia: a prospective study of two UK population-based cohorts |
| title_fullStr | Optimizing midlife metabolic syndrome thresholds for dementia: a prospective study of two UK population-based cohorts |
| title_full_unstemmed | Optimizing midlife metabolic syndrome thresholds for dementia: a prospective study of two UK population-based cohorts |
| title_short | Optimizing midlife metabolic syndrome thresholds for dementia: a prospective study of two UK population-based cohorts |
| title_sort | optimizing midlife metabolic syndrome thresholds for dementia a prospective study of two uk population based cohorts |
| topic | Cardiometabolic risk factors Metabolic syndrome Optimal thresholds Dementia Midlife |
| url | https://doi.org/10.1186/s13195-025-01732-8 |
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