Cardiometabolic factors and risk of dementia in people with type 2 diabetes in England: a large retrospective cohort study

Introduction

People with type 2 diabetes (T2D) have a higher dementia risk. Cardiometabolic factors may influence dementia development, but long-term links among people with T2D remain unclear. Prior studies show mixed findings and have not considered how the time before dementia diagnosis at which cardiometabolic factors are measured affects their association with dementia risk.

Methods

We examined the associations between eight routinely measured cardiometabolic factors (including blood pressure, lipid, and glycemic markers) and the risk of dementia in 249 958 adults with T2D from the Clinical Practice Research Datalink (1999–2018). Multivariable Cox proportional hazards regression was applied with age as the timescale and stratified by follow-up time at 5, 5–10, and ≥10 years before dementia diagnosis. Cardiometabolic factors were analyzed continuously and categorically using clinically relevant cut-offs.

Results

22 492 incident dementia cases were observed (1 257 998 person-years of follow-up). Higher systolic blood pressure was associated with a lower dementia risk, particularly when measured closer to the time of dementia diagnosis. Higher diastolic blood pressure (DBP) (90 vs 80 mm Hg) was associated with a 21% greater risk of dementia (95% CI 15% to 27%). Dementia risk was 32% (27%–36%) lower for those with a body mass index (BMI) ≥30 (vs <25 kg/m²) when measured within 5 years of dementia diagnosis, but 15% (7%–23%) and 43% (31%–56%) higher if measured 5–10 and ≥10 years before diagnosis, respectively. Higher levels of glycemic measures were consistently associated with a greater dementia risk. Findings for total cholesterol and low-density lipoprotein were largely null.

Conclusions

Higher DBP, BMI, and glycemic measures measured over 10 years before dementia diagnosis were linked to a greater dementia risk among adults with T2D. Associations varied depending on when cardiometabolic factors were measured relative to dementia diagnosis, demonstrating the importance of distinguishing potential long-term risk factors from short-term markers of dementia development.

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