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JAMA Intern Med. 2014 Mar;174(3):324-33. doi: 10.1001/jamainternmed.2013.13656.

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.

Collaborators (403)

William JD, Launer LJ, Kramer R, Williamson JD, Miller ME, Coker LH, Lovato J, Lovato L, Hepler J, Felton D, Andrews L, Mayer S, Carter C, Woolard N, Bryan R, Desiderio L, Davatzikos C, Bilello M, Melhem ER, Koka D, Parmpi E, Battapady H, Erus G, Gerstein HC, Yusuf S, Capes S, Punthakee Z, Cukierman-Yaffe T, Vallis M, Hall S, Mackie P, Reiding V, Russo R, Tadeson B, Thompson K, Capes S, Punthakee Z, Smith A, Valla T, Joyce C, Parsons M, Rowe B, Hramiak I, Gehring M, Tereschyn S, Lochnan H, Maranger J, McLean M, Sigal R, Woo V, Berard L, Anderlic T, Bernard A, Mawani AN, Abbott C, Ur E, McCarthy G, Yuille M, Murdock H, Palmer T, Patterson AM, Grimm RH Jr, Kirpach B, Bartkoske MM, Boyce CM, Druckman N, Gillett AM, Levin JA, Livingston GJ, Murray AM, Margolis KL, Truwit C, Kempainen S, Madden M, Hall K, Wood K, Bergenstal R, Cuddihy R, Davick B, List S, Whipple D, Ashanti C, Kendall D, Seaquist ER, Mech MV, Benedict LE, Demmon DJ, Kumar AF, Martinson SM, Miller SA, Pease C, Rao JP, Redmon J, Swanson JE, Wimmer JK, Okorocha Y, Stiles M, Kodl C, Chadha C, Peterson KA, Seaquist LA, Boese C, Mendenhall TJ, Peterson AM, Rudelt A, Schrock TM, Sperl-Hillen J, O'Connor PJ, Busch ME, Chung A, Klein BK, Krugen N, Bunkers-Lawson T, Ekstrom HL, Gunderson HS, Johnson BM, MacIndoe JH, Prewedo DJ, Rawl JL, Roethke CM, Quinlan M, Fox CR, Bate BM, Cao Q, Ohnstad MM, Meyers P, Sivitz WI, Wayson SM, Lower TA, Ochs KA, Wells D, Lazar RM, Slane K, Lopez-Jimenez CR, Hirsch J, Brown TR, Dashnaw SM, Cruz-Lobo J, Schubart UK, Russo J, Vincenty N, Ibarrando K, Alderman MH, Carroll L, Sanguily MJ, Mayer AC, Ramos L, Brillon D, Cordero J, Chiong R, Hyams K, Bastien A, Grudzinski S, Niblack P, Abreu L, Brown K, Casale M, Dougherty D, Linneman D, Salvador MA, Zee P, Hyman D, Atabek D, Miranda J, Kumar I, Baker C, Hill C, Brautigam DF, Fischer R, Scharf DM, Brautigam E, Nunn B, Chiarot M, Flanders C, Goland R, Kringas P, Montes J, Belle J, Berrie N, Getaneh A, Ramirez J, Kranwinkel G, Vasquez E, Donovan DS, Febres G, Hernandez C, Jonaitis MA, Lopez-Jimenez C, Banerji MA, Norton M, Patel P, Hirsch S, Genuth S, Ismail-Beigi F, Thibonnier M, Vargo L, Kelly C, Bongorno T, Dolish A, Pavlik L, Tiktin M, Isteitieh S, Bartlett A, Yee K, Kulow T, Horowitz KA, Sunshine J, Clampitt M, Ismail-Beigi F, Krikorian A, Moore L, Richardson L, Coles-Herman E, Frankino J, Sood A, Hustak L, Julius M, Pavlik L, Ross T, Long L, Sullivan MK, Strauss L, Behm K, Eskandari F, Hall C, Hayes D, Horowitz KA, Isteitieh S, Madhun Z, Seeholzer E, Shina J, Taylor H, Schnall A, Sadler LS, Griffith M, Hornsby A, Klyn K, Ospelt E, Long L, DeSmit M, McCann P, Schmidt NP, Kulow T, Zaletal T, Schnall AM, Dragmen L, Ellert R, Smith J, Leksan J, Sussman T, Ismail-Beigi F, Hustak L, Julius M, Schwing W, Hall C, Horowitz KA, Isteitieh S, Johnson C, Kern E, Richmond MA, Richardson L, Roberts K, Shina J, Suhan P, Taylor H, Watts S, Martin J, Strauss G, Akpunonu B, Franco-Saenz R, Gilmore J, Gilmore M, Ross P, Bauer B, Pop-Busui R, Roman J, Blust Z, Thomas A, Kahkonen DM, Cushman T, Roman M, Stys AM, White K, Austin M, Chatterton C, Francis J, Jones C, Kruger D, McLellan A, Whitehouse F, Higgins E, Levy S, Schoenherr A, Goff DC Jr, Summerson JH, Crago L, Blackwell CS, Bertoni A, Blaine RL, Kirk JK, Spach RL, Williamson J, Calles J, Katula J, Wishnietsky DB, Gordineer L, Ding J, Kaminsky S, Fuller D, Feinglos MN, Jones J, Gedon-Lipscomb G, Atkinson HH, Stanfield J, Delvalle-Fagan T, Pedley CF, Mauney S, Buse JB, Duclos MD, Kirby RE, Goley A, Vukojicik K, Miller JL, Besterman W, Norton SM, Surgener M, Dulin M, Barringer T, Morris C, Norton S, Peace R, Stuart DO, Strickland J, Cummings L, Stanfield J, Peace R, Strickland J, Cummings L, Stanfield J, Crouse JR 3rd, Ellis J, Fonseca V, John-Kalarickal J, Leger SM, Munshi K, Barzilay J, Bader K, Eley M, Probstfield JL, Sullivan MD, Kingry C, Johnson JM, Line A, Corson MA, Knopp R, Lipkin E, Griswold C, Liebert K, Brown A, Juliano D, Kurashige EM, Moberg S, Leader J, Ariani K, Gutierrez H, Failor R, Ellsworth A, Jackson N, Capoccia K, Force R, Macdonald M, Koester S, Pettingill K, Linz PE, Pepper PV, Griffin S, Kozlowski J, Engle M, Gutierrez P, Riddle MC, McDaniel PA, Gammell-Matthews SC, MacNeil B, DesRochers SK, Swift R, Wysham C, Weeks D, Kuntsmann L, Dudl J, Wu P, Lyons L, Murray M, Palma A, Stevenson R, Dailey G, Philas-Tsimikas A, Giannella A, Bravo-Medina A, Jacobson M, Farro E, Cruz S, Juarez N, Dadkhah C.

Author information

1
Roena B. Kulynych Center for Memory and Cognition Research, Department of Internal Medicine, Wake Forest University, Winston-Salem, North Carolina.
2
Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
3
Department of Radiology, University of Pennsylvania Health System, Philadelphia.
4
Division of Public Health Sciences, Department of Social Sciences and Health Policy, Wake Forest University, Winston-Salem, North Carolina.
5
Departments of Neurology and Neurological Surgery, Columbia University College of Physicians and Surgeons, New York, New York.
6
Department of Medicine, McMaster University, Hamilton, Ontario, Canada7Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.
7
Hennepin County Medical Center and Chronic Disease Research Group, Minneapolis, Minnesota.
8
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle.
9
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
10
Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle.
11
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
12
Division of Epidemiology and Community Health, University of Minnesota Medical School, Minneapolis.
13
Kaiser Permanente, Crescent Center Medical Office, Tucker, Georgia.
14
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
15
Cardiology Division, Naval Medical Center San Diego, San Diego, California.

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 =‚ÄČ.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.

PMID:
24493100
PMCID:
PMC4423790
DOI:
10.1001/jamainternmed.2013.13656
[Indexed for MEDLINE]
Free PMC Article
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