Role of age and exposure duration in the association between metabolic syndrome and risk of incident dementia: a prospective cohort study.

Abstract

Background: Metabolic syndrome could be a modifiable risk factor for dementia. However, the effects of age and duration of exposure to metabolic syndrome on dementia risk remains underexplored. The aim of this study was to determine whether the association between metabolic syndrome and risk of dementia differs across mid-life versus late-life, and to explore how duration of metabolic syndrome affects this risk.

Methods: We conducted a population-based prospective study using data from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort. Metabolic syndrome was defined as having at least three of the following: elevated waist circumference, triglycerides, blood pressure, or glycated haemoglobin, or reduced HDL cholesterol. Incident all-cause dementia was ascertained through hospital inpatient, death, and mental health-care records. In full-cohort analyses, we studied 20 150 adults without dementia aged 50-79 years who attended baseline assessments. Cox proportional hazards models were used to estimate the association between metabolic syndrome and dementia in the full sample, and in mid-life (50-59 years and 60-69 years) and late-life (70-79 years). To assess duration of metabolic syndrome, group-based trajectory analysis was performed on 12 756 participants who attended at least two health assessments over 20 years.

Findings: The mean age of participants was 62·6 years (SD 7·5), and 10 857 (54%) were female. Over 25 years of follow-up (mean 18·8 years [SD 6·3]), 2653 (13%) participants developed dementia. In the full cohort, metabolic syndrome was associated with an increased risk of dementia (hazard ratio 1·11, 95% CI 1·01-1·21). In age-specific analyses, the association was similar for participants in late mid-life (age 60-69 years: 1·21, 1·05-1·39) and, although non-significant, in early mid-life (age 50-59 years: 1·12, 0·87-1·43), but attenuated for participants in late-life (age 70-79 years: 0·96, 0·81-1·14). A linear trend was observed between the number of metabolic syndrome components and dementia risk in those aged 60-69 years (p_trend=0·0040), but not in other age groups. In trajectory analysis, a prolonged duration of metabolic syndrome was associated with a significantly increased risk of developing dementia (1·26, 1·13-1·40) when compared to those with consistently low metabolic syndrome. No association was found for increasing metabolic syndrome (1·01, 0·88-1·17).

Interpretation: These findings provide insights into how certain age windows and time periods might differentially affect dementia risk in the context of metabolic syndrome, and highlight the importance of considering age and duration of exposure to metabolic syndrome when devising dementia prevention strategies.

Funding: Canadian Institutes of Health Research-Institute of Aging, Oxford Population Health, and the Nicolaus and Margrit Langbehn Foundation.