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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


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


JAMA Internal Medicine, Volume: 174, No.: 3, Pages.: 324-333

Year of Publication



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] cm(3); 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 Identifier: NCT00000620.;

Bibtex Citation

@article{Williamson_2014, doi = {10.1001/jamainternmed.2013.13656}, url = {}, year = 2014, month = {mar}, publisher = {American Medical Association ({AMA})}, volume = {174}, number = {3}, pages = {324}, author = {Jeff D. Williamson and Lenore J. Launer and R. Nick Bryan and Laura H. Coker and Ronald M. Lazar and Hertzel C. Gerstein and Anne M. Murray and Mark D. Sullivan and Karen R. Horowitz and Jingzhong Ding and Santica Marcovina and Laura Lovato and James Lovato and Karen L. Margolis and Christos Davatzikos and Joshua Barzilay and Henry N. Ginsberg and Peter E. Linz and Michael E. Miller}, title = {Cognitive Function and Brain Structure in Persons With Type 2 Diabetes Mellitus After Intensive Lowering of Blood Pressure and Lipid Levels}, journal = {{JAMA} Internal Medicine} }


aged, antihypertensive agents, blood, blood pressure, brain, cognition, diabetes, diabetes mellitus type 2, drug effects, drug therapy, female, for, humans, hypercholesterolemia, hypertension, intensive, lipids, magnetic resonance imaging, male, middle aged, pathology, people, pharmacology, physiology, psychology, receiving, risk factors, therapeutic use, treatment, treatment outcome, type, with

Countries of Study

Canada, USA

Types of Dementia

Mild Cognitive Impairment (MCI)

Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Risk Factor Modification

Risk Factor Modifications

At risk population