Aims: This study aims to provide an updated systematic review and meta-analysis on the risk of Alzheimer's disease (AD) in patients with metabolic syndrome (MetS) and to analyze the contribution of each MetS component on AD onset.

Data synthesis: The study was performed according to the PRISMA guideline. Data were obtained searching MEDLINE, Scopus, Web of Science, and EMBASE for studies published between January 1, 2010 and July 30, 2020, evaluating the association between MetS and AD risk. A total of 255 articles were retrieved and 6 investigations (4 prospective and 2 retrospective) met the inclusion criteria. Overall, 9.788.021 patients with a mean follow-up of 4.5 years were analyzed. The pooled analysis revealed a slight increased risk of AD in MetS (hazard ratio, HR: 1.10, 95% and confidence interval, CI: 1.05-1.15). Egger's test indicated the absence of publication bias (t = 2.095 and p = 0.104). However, while analysis based on prospective studies failed to show a significant association between MetS and AD (HR: 0.80 and 95% CI: 0.61-1.05), analysis based on retrospective studies demonstrated a significant, slight increased risk (HR:1.11 and 95% CI: 1.08-1.66). With regard to MetS components, the risk was: arterial hypertension, HR: 1.05 (95% CI: 1.04-10.6); hyperglycemia/diabetes, HR: 1.19 (95% CI: 1.18-1.99); low high-density lipoprotein cholesterol (HDL-C), HR: 1.07 (95% CI: 1.06-1.07); hypertriglyceridemia, HR: 1.06 (95% CI: 1.05-1.06); and abdominal obesity, HR: 0.84 (95% CI: 0.74-0.95).

Conclusions: We found a significant association between MetS and AD, mainly driven by large retrospective studies. Our data also support the association of single MetS components with AD incidence, while increased waist circumference seems to have a "protective role" probably due to reverse causality.