Neither intensive blood pressure control nor intensive lipid management slowed cognitive decline in adults with long-standing type 2 diabetes.
Additionally, after 40 months, patients in the ACCORD MIND trial on intensive blood pressure treatment showed significantly more decline in total brain volume than those on a standard blood pressure control program. But it will take much more study to determine exactly what that finding means, Dr. Jeff Williamson and his colleagues reportedon Feb. 3 in JAMA Internal Medicine.
"Although a greater decline in total brain volume is associated with early cognitive impairment, a precursor to dementia, the long-term implications are unknown and remain a focus of ongoing investigation and analyses" wrote Dr. Williamson of Wake Forest University, Winston-Salem, N.C., and his coauthors "Our finding suggests that total brain volume and white matter lesion burden cannot, to date, be used as surrogate markers for cognitive outcomes."
Dr. Jeff Williamson
The team reported outcomes from a substudy of Memory in Diabetes (MIND). MIND itself was a substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and comprised 2,977 participants who had been randomly assigned to receive either intensive glycemic treatment targeting hemoglobin A1c to less than 6.0% or standard treatment targeting HbA1c to 7.0%-7.9%. They were also assigned to either intensive or standard lipid- and blood pressure–lowering treatment arms.
In 2011, the MIND investigators reported that intensive glycemic management didn’t alter the trajectory of cognitive decline.
They did, however, see that total brain volume had declined significantly less in the intensive-therapy group. This led the investigators to suggest that structural changes were preceding cognitive decline and that if the therapy had been extended, a treatment difference might have emerged. The point was moot, however. ACCORD was halted early because those in the intensive therapy group had increased overall mortality, increased hypoglycemic events, weight gain, and no evidence of reaping a cardiovascular benefit.
The newly published data focus on the blood pressure and lipid treatment arms of MIND. The 2x2 design randomized patients to intensive or standard blood pressure control (120 vs. 140 mmHg), or to a statin plus fibrate or statin plus placebo treatment.
Cognition was assessed at baseline, 20, and 40 months. The main measure was the Digit Symbol Substitution Test (DSST), a measure of psychomotor speed and working memory.
Secondary measures included the Stoop Test, the Rey Auditory Verbal Learning Test, and the Mini Mental State Exam.
By 40 months, the DSST scores declined similarly in the standard and intensive treatment groups of both the blood pressure and lipid cohorts. Nor were there any significant between-group differences in any of the other three cognitive measures (JAMA Int. Med. 2014 [doi:10.1001/jamainternmed.2013.13656]).
A subset of patients (378 from the blood pressure arm and 236 from the lipid arm) also underwent magnetic resonance imaging of the brain at baseline and at 40 months. Those in the intensive blood pressure therapy group showed a significantly lower total brain volume than did those in the standard therapy group – a mean of about 4.4 cm3 less. There were no significant brain volume differences in the lipid management cohort.
The team then analyzed this finding in relation to the MRI results of the glycemic control study, which had shown preserved brain volume associated with intensive management in both the blood pressure and lipid therapy groups. "Participants receiving the combination of standard antihypertensive therapy and intensive glycemic control experienced approximately 50% of the decline in total brain volume observed in the other blood pressure trial groups," the authors noted.
The results seem to reinforce the idea that earlier is better when it comes to controlling the cognitive effects of diabetes, they said.
"During the past two decades, the belief that more intensive treatment strategies for controlling type 2 diabetes-related comorbidities, such as hyperglycemia, hyperlipidemia, and hypertension, would reduce clinical complications has driven large investment in new medications for this disease syndrome. However, these results from the ACCORD MIND substudy, along with the other recent ACCORD results, make clear the decreasing returns of intensive medication-based therapy for advanced type 2 diabetes and add further evidence to the need for increased investment in disease prevention and early intervention."
The study was funded by the National Heart, Lung, and Blood Institute. Dr. Williamson had no financial disclosures. Of the other 18 investigators, one reported financial relationships with multiple pharmaceutical companies and one reported receiving consulting fees from Roche.
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