The Effect of Physical Activity on Cognition Relative to APOE Genotype (PAAD-2)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 2
- 主要终点
- Change in performance on the cognitive domain of memory as measured with the Rey-Osterrieth Complex Figure Test
研究概览
简要总结
Physical activity and Alzheimer's disease (PAAD-2) is a randomized control trial that will assess the effects of exercise on middle-aged (40-65 years) cognitively normal adults who have a heightened risk of Alzheimer's disease (AD) due to family history (FH+). The investigators will also assess the extent to which this effect is moderated by apolipoprotein epsilon-4 (APOE4) carrier status, and will gather critical new experimental evidence on the use of physical activity to improve cognitive performance by persons at the greatest risk of Alzheimer's disease.
详细描述
In this study, the investigators follow up on their past research exploring the effects of physical activity on cognitive performance and underlying mechanisms. In particular, the investigators are interested in the potentially different effects that might be realized as a function of a person's genetic risk for Alzheimer's disease. In this study, the investigators extend past work by proposing a randomized clinical trial to: (a) test the causal link between physical activity and cognitive performance in middle-aged adults (40-65 years) with a family history, and (b) determine if the effect is moderated by apolipoprotein epsilon-4 (APOE4) carrier status. The investigators will collect neuroimaging measures of cerebral structure, white matter integrity, and resting state connectivity; assess putative biological markers; and (using moderated mediation analyses) increase understanding of underlying mechanisms and of the extent to which effects are moderated by APOE4 carrier status. To test hypotheses, the investigators will randomly assign 240 cognitively normal, middle-aged adults to a 1-year virtual physical activity program or a usual care control. Those in the intervention will participate in a year-long physical activity program including aerobic exercise performed on your own and resistance exercises led in virtual exercise sessions with an instructor 1 hour/day for 3 days/week for 1 year. Those in the usual care control condition will be asked to maintain their normal lifestyle for one year and then will be given a short-term fitness center membership (contingent upon completion of testing sessions). The investigators will assess cognitive performance at pre-, mid-, and post-test, and obtain MRI scans and blood samples at pre-, mid- and post-test. The investigators will examine the effects of physical activity on cognitive performance and on neurological and biological mechanisms and will explore the moderating role of APOE4.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Care Provider, Outcomes Assessor)
盲法说明
The outcomes assessor will be masked to intervention assignment and APOE4 carrier status. The interventionist will be masked to APOE4 carrier status.
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Family History of Alzheimer's disease, cognitive impairment
- •Able to communicate in English
- •Not currently meeting recommendations for physical activity (the recommendations are to exercise 3 days/week for 30+ minutes per day for longer than 3 months)
- •Willing to be randomized to either study condition
- •Willing to complete all study activities for 1 year
排除标准
- •Meet the criteria for clinical cognitive impairment
- •Unable to perform physical activity due to known cardiovascular, metabolic, or renal disease and are symptomatic or due to orthopedic limitations
- •Self-report history of confounding neurologic, psychiatric, or active severe or functionally disabling neurologic or medical diseases, or any other conditions that might limit exercise or pose a danger to the patient
- •Current use of medications to treat symptoms of Alzheimer's disease, that adversely affect cognition, or that impact heart rate
- •Meet the criteria for depression using the short form of the Center for Epidemiological Studies Depression Scale
- •Traveling for an extended period (>1 month) during the course of the study
研究组 & 干预措施
Usual Care Control (UCC)
Participants in the usual care control will maintain their normal health practices for 1 year. Participants will receive a bi-weekly health newsletter and will be contacted bi-weekly to answer any questions and inquire about the participant's health. Participants self-reported physical activity will be assessed monthly. In this fashion, participants will be contacted by staff every week. Usual care control participants that complete all study related activities including pre-, mid-, and post-test will receive a short-term YMCA membership after post-test.
Physical Activity Condition (PAC)
Subjects will be asked to attend virtual exercise sessions 3 times a week for 1 year.
干预措施: Physical Activity Condition (Behavioral)
结局指标
主要结局
Change in performance on the cognitive domain of memory as measured with the Rey-Osterrieth Complex Figure Test
时间窗: Pretest, 6 months, and 12 months
Change in memory will be assessed by comparing post-, mid-, and pre-test performance on the Rey-Osterrieth Complex Figure Test
Change in performance on the cognitive domain of memory as measured with the Mnemonic Similarity Test
时间窗: Pretest, 6 months, and 12 months
Change in memory will be assessed by comparing post-, mid-, and pre-test performance on the Mnemonic Similarity Test
Change in performance on the cognitive domain of attention as measured with the Paced Auditory Serial Addition Test
时间窗: Pretest, 6 months, and 12 months
Change in attention will be assessed by comparing post-, mid-, and pre-test performance on the Paced Auditory Serial Addition Test
Change in performance on the cognitive domain of working memory as measured with Backward Digit Span
时间窗: Pretest, 6 months, and 12 months
Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Backward Digit Span
Change in performance on the cognitive domain of processing speed as measured with the Stroop Color Test
时间窗: Pretest, 6 months, and 12 months
Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Stroop Color Test
Change in performance on the cognitive domain of executive function as measured with the Flanker test.
时间窗: Pretest, 6 months, and 12 months
Change in executive function will be assessed by comparing post-, mid-, and pre-test performance on the Flanker test.
Change in performance on the cognitive domain of executive function as measured with Matrix Reasoning.
时间窗: Pretest, 6 months, and 12 months
Change in executive function will be assessed by comparing post-, mid-, and pre-test performance on Matrix Reasoning.
Change in performance on the cognitive domain of executive function as measured with Stroop Interference
时间窗: Pretest, 6 months, and 12 months
Change in executive function will be assessed by comparing post-, mid-, and pre-test performance on Stroop Interference.
Change in performance on the cognitive domain of executive function as measured with Dimensional Change Card Sort
时间窗: Pretest, 6 months, and 12 months
Change in executive function will be assessed by comparing post-, mid-, and pre-test performance on Dimensional Change Card Sort
Change in performance on the cognitive domain of memory as measured with the Picture Sequence test
时间窗: Pretest, 6 months, and 12 months
Change in memory will be assessed by comparing post-, mid-, and pre-test performance on the Picture Sequence test.
Change in performance on the cognitive domain of attention as measured with the Forward Digit Span test
时间窗: Pretest, 6 months, and 12 months
Change in attention will be assessed by comparing post-, mid-, and pre-test performance on the Forward Digit Span
Change in performance on the cognitive domain of working memory as measured with List Sort Working Memory
时间窗: Pretest, 6 months, and 12 months
Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the List Sort Working Memory
Change in performance on the cognitive domain of working memory as measured with Spatial Working Memory
时间窗: Pretest, 6 months, and 12 months
Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Spatial Working Memory
Change in performance on the cognitive domain of processing speed as measured with the Wechsler Adult Intelligence Scale (WAIS-IV) Digit Symbol Task
时间窗: Pretest, 6 months, and 12 months
Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Wechsler Adult Intelligence Scale (WAIS-IV) Digit Symbol Task
Change in performance on the cognitive domain of executive function as measured with Trail Making Test Interference
时间窗: Pretest, 6 months, and 12 months
Change in executive function will be assessed by comparing post-, mid-, and pre-test performance on Trail Making Test interference.
Change in performance on the cognitive domain of memory as measured with the Auditory Verbal Learning Test.
时间窗: Pretest, 6 months, and 12 months
Change in memory will be assessed by comparing post-, mid-, and pre-test performance on the Auditory Verbal Learning Test.
Change in performance on the cognitive domain of processing speed as measured with the Trail Making Test A
时间窗: Pretest, 6 months, and 12 months
Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Trail Making Test A
Change in performance on the cognitive domain of processing speed as measured with the Stroop Word Test
时间窗: Pretest, 6 months, and 12 months
Change in working memory will be assessed by comparing post-, mid-, and pre-test performance on the Stroop Word Test
Change in Performance on the Cognitive Domain of Executive Function as Measured With Matrix Reasoning.
时间窗: Pre-Test, Mid-Test (~6 months), and Post-Test (~12 months)
Change in executive function will be assessed by comparing Pre-Test, Mid-Test (\~6 months), and Post-Test (\~12 months) performance on Matrix Reasoning Accuracy from the Virginia Cognitive Aging Project (VCAP). Version O was given at pre, Version A was given at mid, and Version B was given at post. Possible scores are proportions that range from 0-1 (i.e., 0% accuracy to 100% accuracy expressed on a 0.00-1.00 scale) with a higher score being indicative of better performance.
次要结局
- Change in cardiorespiratory fitness(Pretest, 6 months, and 12 months)
- Change in brain activity (resting-state connectivity)(Pretest and 12 months)
- Change in brain morphology (whole brain and hippocampal volumes)(Pretest and 12 months)
- Change in blood biomarkers (BDNF, irisin, IGF-1, glucose, insulin, TNF-⍺, serum amyloid protein (SAP), albumin, ApoE and ⍺-2 macroglobulin)(Pretest and 12 months)