Metabolic syndrome and risk of incident all-cause dementia, Alzheimer’s disease and vascular dementia: a systematic review and meta-analysis of longitudinal studies

Abstract Background Metabolic syndrome (MetS) comprises several co-occurring vascular and cardiometabolic characteristics and might represent a novel modifiable risk factor for dementia, though findings remain inconsistent. To clarify this, we conducted a systematic review and meta-analysis of longitudinal studies investigating the association between MetS with risk of incident all-cause dementia, Alzheimer’s disease and vascular dementia. Methods We searched Medline, Embase and PsycINFO databases (from inception to Feb 19th, 2024) for longitudinal cohort studies investigating the association of MetS with incident all-cause dementia or key subtypes, including Alzheimer’s, vascular, Lewy Body or other dementias. Random-effects models were used to estimate pooled hazard ratios (pHR) and 95% confidence intervals (CI). Risk of bias was assessed using the Quality Assessment Tool for Quantitative Studies. Results Of 4,719 studies identified, fourteen studies met the eligibility criteria. These studies combined included 4,345,741 participants who were initially free of dementia. Pooled estimates showed that, compared to participants with no MetS, those with MetS had a significantly greater risk of incident all-cause dementia (4,307,830 participants, 27,708 cases, pHR: 1.12, 95% CI: 1.08–1.15, I 2 = 12.0%). No significant association was observed for incident Alzheimer’s disease (4,109,436 participants, 14,890 cases, pHR: 0.91, 95% CI: 0.72–1.15, I 2 : 41.0%) or vascular dementia (4,109,436 participants, 2,642 cases, pHR: 1.40, 95% CI: 0.96–2.06, I 2 : 59.0%). Associations remained similar in subgroup analyses restricted to studies reporting results for those aged 65 + years: all-cause dementia (pHR: 1.08, 95% CI: 1.00-1.16, I 2 : 15.0%), Alzheimer’s disease (pHR: 0.85, 95% CI: 0.65–1.11, I 2 : 0.0%), and vascular dementia (pHR: 1.55, 95% CI: 0.71–3.39, I 2 : 75.0%). Conclusions Our findings demonstrate that MetS may be an important risk factor for developing dementia, and represent a potential target for prevention. Further studies are needed to understand the influence of MetS on specific dementia subtypes.