Intensive lowering of blood pressure (BP) and lipids does not appear to reduce cognitive decline in patients with type 2 diabetes, initial results from a randomised prospective study have found.

The trial was conducted at multiple centres in North America, and was one of the sub studies of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial.1 This set out to test the hypothesis that intensive reduction of blood glucose, BP and lipids would improve cardiovascular outcomes in diabetes. The glycaemic study arm with patients treated to tighter HbA1c targets was halted prematurely because of an excess of deaths compared with the control group. No benefits were seen in the other intervention arms, and this finding was consistent with other studies testing the same hypothesis, such as the ADVANCE study.

Patients who were in the ACCORD study were invited to take part in an assessment of cognitive function, to see if intensive treatment of risk factors had a protective effect.

This was called the MIND substudy. The ACCORD MIND glycaemia study has already been published, and showed no such protective effect could be found in patients with tight glycaemic control.² The current paper reports the ACCORD-MIND results for BP and lipid interventions.

Overall, 2,977 patients with type 2 diabetes without evidence of cognitive impairment or dementia and with HbA1c < 7.5% were enrolled in the study. Their mean age was 62 years.

Of these patients 1,439 formed the BP arm of the trial and were randomly assigned to intensive intervention (target systolic BP < 120mmHg) or standard intervention (target systolic BP < 140mmHg).

The remaining 1,538 patients were assigned to the lipid arm where they were randomised to receive a fibrate or placebo. All were taking a statin and had LDL levels < 100 mg/dl.

Cognition was assessed at baseline, 20 months and 40 months. In addition, 503 of the participants underwent MRI at induction into the study and again at 40 months to look for changes in brain volume and other structural measures of brain health.

There were no significant differences in cognitive function between any of the groups in the study. At 40 months the intensive BP intervention arm had lower total brain volumes than the standard BP group, a difference of -4.4 cm3 (95% CI:-7.8 to -1.1, P = 0.01). Fibrate therapy had no effect on brain volume.

Diabetes patients are known to be at increased risk of decline in cognitive function, reduced brain volume and increased white matter lesions in the brain.³ The postulated mechanism for this, as in other diabetes complications, is vascular damage. Diabetes is thought to increase the risk of the repeated micro-strokes that are associated with vascular dementia. Some studies had suggested that intensively addressing the vascular risk factors of BP and lipid levels could prevent this tendency to cognitive decline. The current trial shows no overall reduction in diabetes-related cognitive decline from intensive control of lipids and BP.

There will be discussion about the length of this study – the planned long-term follow-up may show that intensive intervention only exerts a protective effect over a longer period of time. This legacy effect has already been found with respect to vascular outcomes on long-term follow-up of the UKPDS study. As the mean age of the participants was 62, many will only have been in their late 60s when the study finished. Most of our patients do not present to us with dementia until their 70s and 80s; increasing age is the most significant risk factor for developing the condition.

Although this study shows no evidence of benefit so far, I think GPs are likely to continue to treat vascular risk factors in those developing multi-infarct dementia until the evidence becomes clearer. This study suggests there is no virtue in treating beyond the currently accepted targets for BP and blood lipids.

Dr Matthew Lockyer

• Williamson JD, Launer LJ, Bryan N et al for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Memory in Diabetes (MIND) Investigators. Cognitive function and brain structure in persons with type 2 diabetes after intensive lowering of blood pressure and lipid levels. A randomised clinical trial. JAMA Intern Med 2014;174(3)324-333