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Diabetes and Dementia: No Benefit from BP Control

Posted by dlife on Tue, Feb 04, 14, 03:56 PM 0 Comment

February 3, 2014 (MedPage Today) -- Diabetic patients in late middle-age receiving intensive anti-hypertensive therapy in a randomized trial showed the same rates of cognitive decline as those assigned to standard treatment, researchers said.

Among some 3,000 participants in the ACCORD study with no clinical evidence of cognitive impairment or dementia, those randomized to intensive blood pressure-lowering therapy showed a mean decrease in scores on the Digit Symbol Substitution Test (DSST) of 1.86 points after 40 months of follow-up (95% CI 1.27 to 2.46), compared with a decline of 1.61 points in those receiving standard anti-hypertensive treatment (95% CI 1.00 to 2.21, P=0.55), according to Je ff D. Williamson, MD, MHS , of Wake Forest University in Winston-Salem, N.C., and colleagues.

Similar results were seen with three other measures of cognitive function: the Rey Auditory Verbal Learning Test, the Stroop Color-Word Test, and the Mini-Mental State Examination (MMSE), the researchers reported online in JAMA Internal Medicine.

In addition, brain atrophy appeared to progress faster in the intensive-therapy group, with a mean loss of 18.9 mL in total brain volume during the 40-month follow-up, compared with a 14.5-mL decrease in the standard-therapy group (P=0.01).

The negative findings deal a blow to hopes that modifying risk factors for cognitive impairment can slow its onset or progression.

"The expectation that short-term interventions at relatively young ages will reveal major changes in brain structure and function might be too optimistic," wrote two independent researchers, Carole Dufouil, PhD, of INSERM in Bordeaux, France, and Carol Brayne, MD, of the University of Cambridge in England, in an accompanying commentary.

In the study, which also examined effects of interventions aimed at glycemic and lipid control, patients were randomized to receive anti-hypertensive therapy to achieve a systolic blood pressure target of 140 mm Hg or less (standard) versus 120 mm Hg or less (intensive).

If anything, the study suggested that the aggressive management of blood pressure may have had deleterious effects, given the small but statistically significant acceleration in brain atrophy in that group, Dufouil and Brayne indicated. "Enthusiastic control of blood pressure later in life should be pursued with caution and based on existing evidence, not extrapolated benefits," they wrote.

On the other hand, James Leverenz, MD, of the Cleveland Clinic, told MedPage Today in an interview that 40 months of follow-up may not have been enough to see effects of the intervention on cognition. He also said the DSST and the other assessments may not have been sensitive enough to pick up the relatively small changes that could be expected with this amount of follow-up.

"I don't think the story is done here yet," he said.

A total of 10,251 patients had participated in ACCORD, which was designed to evaluate the effects of aggressive treat-to-target approaches in diabetic patients for blood sugar and pressure and dual- versus single-drug cholesterol-lowering therapy. Of 5,575 who were older than 55 and therefore eligible for a substudy called MIND, designed to assess additional cognitive and brain structural outcomes, 2,977 agreed to participate. Their mean age was 62.

Intensive glucose control was stopped prematurely in the study because of increased mortality. The current analysis focused on the effects of aggressive blood pressure and lipid management.

Adding fenofibrate to simvastatin (Zocor) in ACCORD-MIND participants had little effect on total or LDL cholesterol levels, compared with placebo plus simvastatin, and there was no difference between these groups in any of the cognitive outcomes or in brain volume trajectories.

The intensive anti-hypertensive treatment was effective in reducing blood pressure to levels well below those seen with standard treatment. At 40 months, mean systolic pressure in the intensive treatment group was 119 mm Hg versus 133 with standard therapy.

For cognitive outcomes, differences between blood-pressure management groups were neither statistically nor clinically meaningful. For example, MMSE scores declined from baseline by 0.25 points in the aggressive-therapy group versus 0.30 points with standard treatment (P=0.070).

Only in the Stroop test was there a hint of substantive benefit for aggressive treatment. In that group, scores (which reflect dysfunction, such that a decrease represents clinical improvement) fell 1.50 points, compared with a 0.46-point decline with standard therapy (P=0.16).

Leverenz told MedPage Today that, with the longer follow-up planned for the study, a cognitive benefit may still become apparent. "We may be able to see patients, for example, transitioning into dementia or more severe memory impairment, and there we may see some effect," he said.

He also noted that the study's focus on individuals with established diabetes (mean duration of disease 10 years, mean HbA1c 8.3%) restricted the interpretation.

"The generalizability to individuals without diabetes is very limited," Leverenz said.

The study was funded by the National Heart, Lung, and Blood Institute.

Study authors reported relationships with GlaxoSmithKline, Sanofi, Eli Lilly, Novo Nordisk, AstraZeneca, Bristol-Myers Squibb, Roche, Medtronic, Merck, Bayer, Bioavail, Janssen-Ortho, Pronova, Boehringer Ingelheim, Solvay, Servier, Takeda, Abbott, Pfizer, Isis/Genzyme, and Regeneron.

Dufouil and Brayne declared they had no relevant financial interests.

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