Cognitive Function and Brain Structure in Persons With Type 2 Diabetes Mellitus After Intensive Lowering of Blood Pressure and Lipid Levels: A Randomized Clinical Trial

Study Questions:

What is the effect of intensive therapy for hypertension and combination therapy with a statin plus a fibrate on the risk of decline in cognitive function and total brain volume (TBV) in patients with type 2 diabetes mellitus (T2DM)?


This was a North American multicenter clinical trial including 2,977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c (HbA1c) levels <7.5% randomized to a systolic blood pressure (BP) goal of <120 versus <140 mm Hg (n = 1,439), or to a fibrate versus placebo in patients with low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dl (n = 1,538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. Cognition was assessed at baseline and 20 and 40 months. A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health.


Baseline mean HbA1c level was 8.3%; mean age, 62 years; and mean duration of T2DM, 10 years. At 40 months, no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial. At 40 months, TBV had declined more in the intensive versus standard BP-lowering group (difference, −4.4 [95% confidence interval, −7.8 to −1.1] cm3; p = 0.01). Fibrate therapy had no effect on TBV compared with placebo.


The authors concluded that in participants with long-standing T2DM, intensive BP control and fibrate therapy in the presence of controlled LDL-C levels did not produce a measurable effect on cognitive decline at 40 months of follow-up.


The present study reports that intensive BP management to a target systolic BP of <120 mm Hg and fibrate therapy in the context of LDL-C level control are not effective in reducing cognitive decline in persons with poorly controlled T2DM at high risk for cardiovascular disease. These results should not be construed to negate other evidence that intensive strategies to control BP and lipid levels may be indicated for other conditions such as stroke or coronary heart disease. Overall, these results highlight the decreasing returns of intensive medication-based therapy for advanced T2DM and emphasize the need to focus on diabetes prevention and early intervention.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Hypertension, Sleep Apnea

Keywords: Coronary Artery Disease, Stroke, Cognition, Memory, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Diabetes Mellitus, Type 2, Coronary Disease, Blood Pressure, Cognition Disorders, Metabolic Syndrome X, Cholesterol, Dyslipidemias, Dementia, Cardiovascular Diseases, Hypoglycemic Agents, Diabetic Angiopathies, Hypertension

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