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Cited by 187Dementia and Cognitive Impairment ResearchDiabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and Lipoproteins

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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

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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.·2014·JAMA Internal Medicine
DOI 10.1001/jamainternmed.2013.13656PMC PMC4423790
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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] 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 clinicaltrials.gov Identifier: NCT00000620.

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Authors
Williamson, J. D., Launer, L. J., Bryan, R. N., Coker, L. H., Lazar, R. M., Gerstein, H. C., Murray, A. M., Sullivan, M. D., Horowitz, K. R., Ding, J., Marcovina, S., Lovato, L., Lovato, J., Margolis, K. L., Davatzikos, C., Barzilay, J., Ginsberg, H. N., Linz, P. E., & Miller, M. E.
Affiliations
  • Wake Forest University Health Sciences (US)
  • National Institutes of Health (US)
  • University of Pennsylvania Health System (US)
  • Columbia University Irving Medical Center (US)
  • Population Health Research Institute (CA)
  • Hennepin County Medical Center (US)
  • University of Washington (US)
  • Case Western Reserve University (US)
  • University of Minnesota (US)
  • Kaiser Permanente (US)
  • Naval Medical Center San Diego (US)
Corresponding author
Williamson, Jeff D.
ORCID
Venue
JAMA Internal Medicine
Publisher
American Medical Association (AMA)
Published
2014-03-01
Volume
174
Issue
3
Pages
324
ISSN
2168-6106 (ISSN-L)
DOI
10.1001/jamainternmed.2013.13656
PMC
PMC4423790
OpenAlex
W2110109090
Cited by
187
References
32
Citations by year
2026: 6 · 2025: 12 · 2024: 7 · 2023: 12 · 2022: 9 · 2021: 19 · 2020: 15 · 2019: 28 · 2018: 19 · 2017: 19 · 2016: 11 · 2015: 16 · 2014: 13
FWCI
15.00
Type
journal article
Language
en
Open access
Locations
  • JAMA Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HHSN268201100027C)
  • National Institute of General Medical Sciences (U54GM104940)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, cognitive decline, total brain volume, brain structure, intensive blood pressure control, systolic blood pressure, fibrate therapy, statin therapy, LDL cholesterol, white matter lesions, cognitive function, brain atrophy, hypertension, lipid-lowering therapy, dementia risk
MeSH terms
Aged, Antihypertensive Agents, Blood Pressure, Brain, Cognition, Diabetes Mellitus, Type 2, Female, Humans, Hypercholesterolemia, Hypertension, Lipids, Magnetic Resonance Imaging, Male, Middle Aged, Risk Factors, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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