Investigating the relationship between metabolic syndrome and the risk of developing dementia
Bibliographic record
Abstract
BACKGROUND: Metabolic syndrome (MetS) may be a risk factor for dementia, however, the relationship remains inconclusive. This thesis sought to clarify the association between MetS and incident dementia. METHODS: First, a systematic review was conducted (up to Feb-2022), identifying prospective studies evaluating associations of MetS and risk of incident dementia. Second, UK-Biobank prospective analyses of 176,249 dementia-free adults aged ≥60 years with up to 15-years of follow-up investigated associations of MetS (defined using the 2009 Harmonized Criteria) with incident all-cause dementia (ascertained through medical records) using multivariable Cox-regression. Third, EPIC-Norfolk prospective analyses were conducted in 20,150 adults (50-79 years) with up to 25-years of follow-up, employing similar methods as Objective 2, and additionally exploring the impact of age and duration/trajectory of living with MetS on dementia risk. Group-based trajectory modelling was performed to identify MetS trajectories. Fourth, an updated systematic review and meta-analysis was performed, incorporating UK-Biobank and EPIC-Norfolk findings, plus newly published literature (up to Feb-2024). Fifth, associations of MetS with neuroimaging and cognition were explored in 37,395 dementia-free adults from UK-Biobank using multivariable linear-regression. RESULTS: The systematic review revealed inconsistent evidence, owing to small sample sizes, short follow-up, and inadequate confounder adjustments across studies. In UK-Biobank analyses, MetS was associated with a 12% increased risk of all-cause dementia (HR, 1.12, 95%CI: 1.06-1.18); risk also varied by follow-up length, number of MetS components, and APOE-ε4 carrier status. EPIC-Norfolk analyses found similar trends, and additionally revealed that mid-life MetS was associated with dementia risk (HR, 1.21 [1.05-1.39]), but was attenuated in late-life (HR, 0.96 [0.81-1.14]). A prolonged MetS duration was also associated with heightened dementia risk (HR, 1.26 [1.13-1.40]). In meta-analyses, MetS was associated with all-cause dementia (pHR, 1.12, [1.08-1.15]), but not Alzheimer’s (pHR, 0.91 [0.72-1.15]) or vascular dementia (pHR, 1.40 [0.96-2.06]). Lastly, MetS was associated with lower total and region-specific brain volumes, increased cerebrovascular pathology, and poorer performance across all cognitive domains. CONCLUSIONS: This thesis provides robust evidence indicating that MetS is an independent risk factor for dementia. Targeting MetS might be a useful strategy for dementia prevention. Further research is necessary to explore these associations in diverse populations and understand the pathways linking MetS to different dementia subtypes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.026 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.006 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".