Abstract
Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive (INT) glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial. A battery of neuropsychological tests [digit span, digit symbol substitution (DSym), and Trails-making Test-Part B (TMT-B)] was administered at baseline in ~1700 participants and repeated at year 5. Thirty-seven risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses. The mean age-adjusted DSym or TMT-B declined significantly in all study participants (P < 0.001). Randomized INT glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta = -0.028; P = 0.0057), lower baseline diastolic blood pressure (BP; beta = 0.028; P = 0.002), and baseline calcium channel blocker medication use (beta = -0.639; P < 0.001). Higher baseline pulse pressure was significantly associated with decline in age-adjusted TMT-B suggesting a role for both higher systolic and lower diastolic BPs. Baseline thiazide diuretic use (beta = -0.549; P = 0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post-baseline systolic BP-lowering was significantly associated (P < 0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride-lowering (P = 0.045) and decline in digit symbol substitution task performance. A 5-year period of randomized INT glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic BPs as well as plasma triglycerides appeared as modifiable risk factors of the rate of cognitive decline in older adult type 2 diabetes.
Highlights
Diabetes is associated with a twofold increased risk for age-related cognitive decline or dementia [1, 2]
Baseline clinical characteristics previously reported in the study population did not differ significantly by randomized glycemic treatment group, including mean (SD): age 60.4 (8.7) years, body mass index 31.3 (3.5) kg/m2, hemoglobin A1c 9.4 (2.0)%, diabetes duration 11.4 (7.5) years, systolic blood pressure (BP) 132 [17] mmHg, diastolic BP 76 [10] mmHg, or total cholesterol concentration 184 [47] mg/ dL [6]
There was no significant difference in the baseline scaled digit span (DS), digit symbol substitution, or Trails-making Test-Part B (TMT-B) score in patients assigned to STD or INT glycemic control (Table 1)
Summary
Diabetes is associated with a twofold increased risk for age-related cognitive decline or dementia [1, 2]. The key risk factors and underlying mechanisms contributing to accelerated cognitive aging in adult T2DM remain largely undefined. Type 2 diabetes and age-related cognitive decline share several underlying risk factors, including obesity, hypertension, and hyperlipidemia. Few clinical trials have addressed whether randomization to intensive (INT) glycemic control may slow the rate of cognitive decline [5]. The Veterans Affairs Diabetes Trial (VADT) randomized 1791 older adults with T2DM to standard (STD) or INT glycemic treatment [6]. The current study is from a planned secondary analysis to the VADT designed to test whether INT glycemic treatment slows cognitive decline in older adult T2DM. The neuropsychological tests, digit span (DS), digit symbol substitution task (DSym), and Trails-making Test-Part B (TMT-B) were administered at baseline and again at the year 5 study visit in all available participants
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