• Cognitive decline: rate of decline in tests of memory and executive function in the glycemic treatment group [ Time Frame: Baseline, 20 months and 40 months ] [ Designated as safety issue: No ]
• MRI brain changes: total brain volume (cerebral atrophy) in the glycemic treatment group [ Time Frame: Baseline and 40 months ] [ Designated as safety issue: No ]

• Cognitive decline: rate of decline in tests of memory and executive function in the glycemic treatment group over a 4 year period
• MRI brain changes: total brain volume (cerebral atrophy) in the glycemic treatment group over a 4 year period

• Cognitive decline: rate of decline in tests of memory and executive function in the blood pressure and lipid treatment groups over a 4 year period [ Time Frame: Baseline, 20 months and 40 months ] [ Designated as safety issue: No ]
• MRI brain changes: total brain volume (cerebral atrophy) in the blood pressure treatment group over a 4 year period [ Time Frame: Baseline and 40 months ] [ Designated as safety issue: No ]

• Cognitive decline: rate of decline in tests of memory and executive function in the blood pressure and lipid treatment groups over a 4 year period
• MRI brain changes: total brain volume (cerebral atrophy) in the blood pressure treatment group over a 4 year period

The purpose of this study is to test whether the rate of cognitive decline and structural brain change in people with diabetes treated with standard care guidelines is different than in people with diabetes treated with intensive care guidelines.

Type 2 diabetes and cognitive impairment are two of the most common chronic conditions found in persons 60 years and older. Approximately 18%-20% of older persons suffer from diabetes. And, in the general population, the prevalence of cognitive impairment, measured with the simple Mini-Mental State Exam, increases steadily from 5% at 65 years to 15% percent at 80 years of age. Many persons with cognitive impairment go on to develop dementia, which doubles in incidence and prevalence every additional 5 years of age. Studies suggest diabetes is one risk factor for cognitive impairment and dementia.

Further, the brains of people with diabetes are at risk for complications following repeated hypoglycemic events. Magnetic Resonance Imaging (MRI) provides a measure of the structural changes in the brain that form the anatomical substrate for cognitive decline and dementia. At present there are a few MRI studies showing people with diabetes have increased risk for brain atrophy and (mainly silent) lacunae.

The comparison of standard diabetes care with intensive diabetes care will be made in a sub-sample of 2800 people (including 640 for MRI) with diabetes currently participating in the ongoing National Heart Lung and Blood Institute (NHLBI) Action to Control Cardiovascular Risk in Diabetes (ACCORD). ACCORD is designed to evaluate whether more intensive glucose, blood pressure and lipid management can reduce cardiovascular disease in people with diabetes.

Participants in ACCORD-MIND will have already been randomly assigned to either the intensive or standard diabetes care in the ACCORD trial, and will already have been randomized to either the blood pressure or lipid intervention arms (see NCT00000620). ACCORD-MIND will test these patients for cognitive function and changes in brain structure.

Tests of cognitive function measure memory and executive function, which includes speed of processing, attention, planning, and concentration. They are indicators of how well a person performs various tasks in daily life. Cognitive impairment is also predictive of future onset of dementia. In diabetes, cognitive impairment may compromise an individual's ability to manage his/her disease, an important factor that should be incorporated into an analysis of the trial efficacy.

MRI is a safe, non-invasive method to assess the structural characteristics of the brain. With MRI, investigators may begin to identify vascular lesions and brain atrophy that form the anatomical basis for cognitive changes that may be associated with the ACCORD treatments.

• Atherosclerosis
• Cardiovascular Diseases
• Hypercholesterolemia
• Hypertension
• Diabetes Mellitus
• Coronary Disease

• Drug: hypoglycemic agents
• Drug: hydroxymethylglutaryl-CoA Reductase inhibitors
• Drug: antihypertensive agents
• Drug: fibrates

• Active Comparator: Standard diabetes treatment--HbA1c Target 7.0-7.9%
• Experimental: Intensive diabetes treatment--HbA1c Target 6.0%
• Active Comparator: Standard lipid treatment--a statin for treatment of LDL-C
• Experimental: Intensive lipid treatment--a fibrate to raise HDL-C/lower triglyceride levels plus a statin for treatment of LDL-C
• Active Comparator: Standard blood pressure treatment--target systolic blood pressure (SBP) of < 140 mm Hg
• Experimental: Intensive blood pressure treatment--target systolic blood pressure (SBP) of < 120 mm Hg

• Williamson JD, Miller ME, Bryan RN, Lazar RM, Coker LH, Johnson J, Cukierman T, Horowitz KR, Murray A, Launer LJ; ACCORD Study Group. The Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Study (ACCORD-MIND): rationale, design, and methods. Am J Cardiol. 2007 Jun 18;99(12A):112i-122i. Epub 2007 Apr 12.
• Launer LJ, Oudkerk M, Nilsson LG, Alperovitch A, Berger K, Breteler MM, Fuhrer R, Giampaoli S, Nissinen A, Pajak A, Sans S, Schmidt R, Hofman A. CASCADE: a European collaborative study on vascular determinants of brain lesions. Study design and objectives. Neuroepidemiology. 2000 May-Jun;19(3):113-20.
• Launer LJ. Diabetes and brain aging: epidemiologic evidence. Curr Diab Rep. 2005 Feb;5(1):59-63. Review.

Inclusion Criteria:

• Fulfills criteria for inclusion in the ACCORD main trial
• At least 55 years of age
• English or Spanish is usual language
• Agrees to identify a personal contact who has frequent interaction with participant in order to provide data as needed

Exclusion Criteria:

• Fulfills criteria for exclusion in the ACCORD main trial
• Cancer diagnosed and treated within the past 5 years that, in the judgment of clinical study staff, would compromise a participant's ability to comply with the protocol and complete the trial (exceptions would include skin cancer, early-stage prostrate cancer, etc.).
• Any condition that, in the judgment of the clinical study staff, would preclude full participation in the study (e.g. clinical evidence of dementia, excessive use of alcohol, any visual or hearing impairment that could compromise assessment of cognitive function).