Falling blood pressure and BMI in T2D may signal early dementia

People with type 2 diabetes are nearly twice as likely to develop dementia, but the reasons for this connection are unclear. Dementia has a long preclinical phase, so changes in cardiometabolic measurements might indicate early disease rather than causes.

Few studies consider how long before diagnosis these measurements were taken. This CPRD analysis looked at eight common cardiometabolic factors. It also grouped the results based on how long the follow-up was.¹

Nearly 250,000 adults, stratified by how long before diagnosis¹

• 249,958 people aged ≥45 years diagnosed with T2D between 1 January 1999 and 31 December 2018.

• Stratified by follow-up time: under 5 years (n=143,257), 5 to 10 years (n=71,075), 10 years or more (n=35,626).

Diastolic pressure carried the long-term signal, not systolic¹

• A SBP of ≥140 mm Hg was associated with a 26% lower risk of dementia compared to a SBP of <130 mm Hg.

• The inverse association was consistent across subcohorts and most pronounced when SBP was measured within 5 years of diagnosis (29%, 18% and 20% lower risk in the under 5 year, 5 to 10 year and 10 year or more subcohorts respectively).

• DBP of 90 versus 80 mm Hg was associated with a 21% greater risk of dementia (95% CI 15% to 27%).

• Categorically, DBP 80 to 89 mm Hg and ≥90 mm Hg were associated with 4% and 21% higher risk respectively, relative to <80 mm Hg.

The authors interpret the systolic finding as reverse causation rather than a protective effect, and suggest DBP may be the better long-term indicator of the two.¹

The BMI association reversed with measurement timing¹

• BMI ≥30 kg/m² was associated with a 10% lower risk of dementia versus <25 kg/m² in the full cohort.

• The same comparison reversed with timing: 32% lower (27% to 36%) when measured within 5 years of diagnosis, 15% higher (7% to 23%) at 5 to 10 years, and 43% higher (31% to 56%) at 10 years or more.

The authors attribute the short-term pattern to accelerated weight loss preceding diagnosis, consistent with their earlier 20-year trajectory analysis.²

Higher glycaemic measures were consistently associated with greater risk¹

• FPG >8.5 mmol/L was associated with a 13% higher risk versus <7.0 mmol/L, increasing to 6%, 8%, and 24% higher across subcohorts with longer follow-up.

• HbA1c >58 mmol/mol was associated with a 7% higher risk versus <48 mmol/mol, while 48 to 58 mmol/mol was associated with a 6% lower risk. The association with higher HbA1c strengthened with longer follow-up - however, in a competing-risk model accounting for death, the HbA1c association was no longer significant (1.02, 95% CI 0.98 to 1.06).

Lipid findings were largely null, except HDL at ten years¹

• Total cholesterol >5.0 mmol/L and LDL >3.0 mmol/L were non-linearly associated with greater risk in the full cohort, attenuating with longer follow-up. No association was found using thresholds.

• HDL ≥1.0 mmol/L was associated with a 12% lower risk at 10 or more years of follow-up. The difference within 10 years of diagnosis was not statistically significant.

Relevance in primary care

Higher DBP, BMI and glycaemic levels measured more than ten years before diagnosis were associated with greater dementia risk, but the direction of association varied by timing. The authors suggest that declines in blood pressure, BMI and glycaemic measures in later life may reflect emerging cognitive decline rather than improved control, and could support earlier identification. In an older patient with type 2 diabetes whose weight, blood pressure and HbA1c are all drifting down without a clear explanation, this pattern is worth noting.

References

1. Lai HTM, Chang K, Sharabiani MTA, et al. Cardiometabolic factors and risk of dementia in people with type 2 diabetes in England: a large retrospective cohort study. BMJ Open Diabetes Res Care 2026;14:e005743. doi: 10.1136/bmjdrc-2025-005743

2. Lai HTM, Chang K, Sharabiani MTA, et al. Twenty-year trajectories of cardio-metabolic factors among people with type 2 diabetes by dementia status in England: a retrospective cohort study. Eur J Epidemiol 2023;38:733-44. doi: 10.1007/s10654-023-00977-7