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

Jeff D. Williamson, Lenore J. Launer, Nick Bryan, Laura H. Coker, Ronald M. Lazar, Hertzel C. Gerstein, Anne M. Murray, Mark D. Sullivan, Karen R. Horowitz, Jingzhong Ding, Santica Marcovina, Laura Lovato, James Lovato, Karen L. Margolis, Christos Davatzikos, Joshua Barzilay, Henry N. Ginsberg, Peter E. Linz, Michael E. Miller

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

IMPORTANCE: Persons with type 2 diabetes mellitus (T2DM) are at increased risk for decline in cognitive function, reduced brain volume, and increased white matter lesions in the brain. Poor control of blood pressure (BP) and lipid levels are risk factors for T2DM-related cognitive decline, but the effect of intensive treatment on brain function and structure is unknown. OBJECTIVE: To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume (TBV) in patients with T2DM. DESIGN, SETTING, AND PARTICIPANTS: A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c (HbA1c) levels less than 7.5% randomized to a systolic BP goal of less than 120 vs less than 140 mm Hg (n = 1439) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL (n = 1538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. MAIN OUTCOME MEASURES: 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. RESULTS: 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 vs standard BP-lowering group (difference, -4.4 [95% CI, -7.8 to -1.1] cm3; P = .01). Fibrate therapy had no effect on TBV compared with placebo. CONCLUSIONS AND RELEVANCE: In participants with long-standing T2DM and at high risk for cardiovascular events, intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up. Intensive BP control was associated with greater decline in TBV at 40 months relative to standard therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000620

Original languageEnglish (US)
Pages (from-to)324-333
Number of pages10
JournalJAMA internal medicine
Volume174
Issue number3
DOIs
StatePublished - Mar 2014

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