Metabolomics of Neurocognitive Risk for Dementia in Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 417
- 试验地点
- 1
- 主要终点
- Rey Auditory Verbal Learning Test (RAVLT)
研究概览
简要总结
The study team will evaluate whether metabolomic signatures of neurocognitive decline trajectories are exacerbated by the presence of type 2 diabetes mellitus (T2D) and whether these signatures contribute in part, to ethnic disparities in cognitive decline between European Americans and African Americans with T2D.
详细描述
Aim 1. Re-examine the Diabetes Heart Study Memory IN Diabetes (DHS MIND) cohort for progression of neurocognitive decline using an established cognitive battery, literacy testing, and adjudicated physician diagnosis of dementia.Another neurocognitive evaluation will be completed in European-American and African-American DHS MIND participants, providing longitudinal follow-up more than eight years after initial assessment. The cognitive battery will reassess domains of executive function, memory, and global cognition. In addition, a clinical exam will include a literacy evaluation to circumvent the shortcomings of differences in educational attainment among participants. A physician adjudicated assessment of cognitively normal, mild cognitive impairment, or dementia will be obtained. Cognitive evaluations will inform epidemiological analyses regarding cross-sectional and trajectories of cognition decline relative to existing and repeat measures of cardio-metabolic risk factors.
Aim 2. Examine the metabolomic basis of neurocognitive measures in people with T2D. The presence of T2D, cardiovascular disease and reduced kidney function are significant risk factors for development of cognitive impairment. These risk factors are enriched in the DHS and lack early diagnostic tools. Untargeted metabolomic profiling offers the potential to identify relevant biomarkers that could impact the diagnosis, prognosis, and treatment of cognitive decline. This will be accomplished through untargeted metabolomic analysis of European American and African American DHS MIND participants using stored samples from baseline visits acquired more than 10 years prior to the current (repeat) neurocognitive assessment. These data will be used to A) provide information on novel mechanistic insights into cognition and trajectories of cognitive decline, B) develop a risk prediction model using the baseline exam, and C) validate extremes of neurocognitive performance using longitudinal assessments while examining ancestry/ethnic-specific differences.
Aim 3. Comprehensive genetic analysis of DHS participants to examine the genetic architecture of metabolomic signatures associated with the trajectories of neurocognitive decline. Existing genome-wide data will be used to map regions of the human genome that contain loci contributing to measures of neurocognition and metabolomics signatures of change in these variables through longitudinal assessment. Causal effect modeling will validate the association of modifiable exposures, i.e. genetic markers and metabolites on the outcome (i.e. trajectories of neurocognitive decline).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At the baseline visit, European American and African American individuals with T2D must have had diabetes diagnosed after the age of 30, 3 years disease duration and lack historical evidence of diabetic ketoacidosis.
排除标准
- •At the baseline visit, participants with pre-existing kidney disease, defined as a serum creatinine concentration >1.5 mg/dl or blood urea nitrogen >35 mg/dl were excluded due to the elevation of serum AGE levels in individuals with kidney disease.
结局指标
主要结局
Rey Auditory Verbal Learning Test (RAVLT)
时间窗: Day 1
A word recall list that measures verbal learning and memory. Involves immediate and delayed recall. Score range is 0-75, 75 is the best possible score.
Digit Symbol Coding Task (DSC)
时间窗: Day 1
DSC is a subtest of the Wechsler Adult Intelligence Scale III or IV. It is used to access visual motor speed. Score range 0-133, 133 is the best possible score.
Montreal Cognitive Assessments (MoCA)
时间窗: Day 1
Measures general cognitive and executive function, has increased sensitivity for detecting early cognitive impairment.Score range is 0-30, 30 is the best possible score.
Wide Range Achievement Test 4 (WRAT 4)
时间窗: Day 1
Word reading subtest to measure letter and word decoding through word recognition and letter identification. Score range is 0-70, 70 is the best score possible.
Modified Mini-Mental State Exam (3MSE)
时间窗: Day 1
Measures general cognitive function. Score range is 0-100, 100 is the best possible score.
Stroop subtests 1, 2 and 3
时间窗: Day 1
Measures executive function by determining interchanging word and color challenges. Score range 0-420 seconds, the lower time point is the best.
Category Fluency for Animals
时间窗: Day 1
Measures verbal fluency and language aspects of executive function by asking participant to name as many unique items as possible in a category ie. animals. Score 0-26, the best possible score is 26.
次要结局
- Craft Story Recall (Immediate/Delayed)(Day 1)
- Trail Making Test(Day 1)
- Number Span Test (Forward/Backward)(Day 1)