| Summary: | <p><strong>BACKGROUND:</strong> 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.</p>
<p><strong>METHODS: First</strong>, a systematic review was conducted (up to Feb-2022), identifying prospective studies evaluating associations of MetS and risk of incident dementia. <strong>Second</strong>, 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. <strong>Third</strong>, 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. <strong>Fourth</strong>, an updated systematic review and meta-analysis was performed, incorporating UK-Biobank and EPIC-Norfolk findings, plus newly published literature (up to Feb-2024). <strong>Fifth</strong>, associations of MetS with neuroimaging and cognition were explored in 37,395 dementia-free adults from UK-Biobank using multivariable linear-regression.</p>
<p><strong>RESULTS:</strong> 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.</p>
<p><strong>CONCLUSIONS:</strong> 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.</p>
|
|---|