RCT of Two Speed of Processing Modes to Prevent Cognitive Decline in Older Adults

描述（由申请人提供）：本申请涉及广泛的挑战领域05，比较有效性研究，具体的挑战主题AG-102，残疾预防和风险因素减少策略。NIA的联系人是Georgeanne Patmios女士，301-496-3138,patmiosg@nia.nih.gov。挑战主题05-AG-102呼吁进行随机对照试验（rct）来评估相互竞争的干预措施或干预措施交付模式的相对有效性。05-AG-102的主要目标是预防认知障碍，从而改善健康结果，包括改善生活质量，降低死亡率，发病率和疾病进展，降低医疗保健成本，并改善选定的社会和行为维度。迄今为止进行的规模最大、最严格的随机对照试验（RCT）涉及长期随访，是针对独立和重要老年人的高级认知训练（ACTIVE）研究。尽管所有三种主动认知训练干预（记忆、推理和处理速度）都能有效地提高他们的目标能力，但处理速度组的收益最大，87%的参与者表现出可靠的改善。我们还显示了ACTIVE的处理速度干预（但对记忆或推理干预没有影响）对各种健康结果的临床显着影响，包括：(1)预测医疗费用降低3% (p = 0.012)；(2)全球健康相关生活质量下降的风险降低38% (HRQoL; p = 0.004)；(3)抑郁症状恶化的风险降低30% (p = 0.012)；(4)发生疑似临床抑郁症的风险降低38% (p < 0.01)；(5)自我评估健康状况的改善，可转化为五年死亡率绝对降低0.8%，相对死亡率降低10% (p < 0.05)；(6)内部控制点有意义改善的可能性增加64% （p < 0.05）。尽管处理干预速度的这些影响的规模，多样性和持久性，但在广泛传播之前需要进一步的研究，原因有三。首先，ACTIVE依赖于无接触控制组而不是注意力控制组，这增加了安慰剂效应的可能性。其次，虽然强化训练随机提供给60%的ACTIVE参与者，但它是有条件的，完成10次基线训练中的80次，混淆了强化效应和依从性效应。第三，现在有一种新的、增值版的处理速度软件，几乎可以在任何家用电脑上使用，因此可以大大降低交付成本，方便个人剂量和持续的助推器维护，但没有公开的证据表明增值版与原始版本一样有效。因此，我们的具体目标是通过一项为期一年的随机对照试验来克服这些局限性，该随机对照试验可以在NIH挑战基金的两年期限内完全完成。我们将900名年龄在50岁及以上的参与者随机分为三组。G1组（N=400）将在10个现场疗程中接受与ACTIVE相同的增值处理干预，并进一步随机分配到一半（G1a）未接受强化治疗，一半（G1b）在11个月时接受现场强化治疗。G2组（N=250）将作为注意力控制组，并将接受10个使用电脑填字游戏的现场会议。G3组（N=250）将在现场演示如何操作增值速度处理软件，然后让他们回家在自己的个人电脑上随心所欲地使用它。我们的主要结果测量是处理速度，我们将使用几个可靠和有效的工具来提供多维评估，包括有用的视野测试，符号数字模式测试，轨迹测试，控制口头单词联想测试，数字警惕性测试，以及Stroop颜色和单词测试。我们对这些主要结果测量有七个假设，将使用残差变化评分多元线性回归模型对连续结果进行检验，多元逻辑回归模型对二元（阈值变化）结果进行检验，泊松或负二项回归模型对计数测量进行检验。我们还将评估对几个次要结局的影响，包括HRQoL、医疗保健利用、抑郁症状、功能能力、感知压力、自我效能和控制感。最后，我们将对50-64岁的参与者进行分层分析，并对65岁及以上的参与者进行单独分析，以确定加工速度干预的效应大小是否因年龄组而异。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area 05, Comparative Effectiveness Research, specific Challenge Topic AG-102, Prevention and Risk Factor Reduction Strategies for Disabilities. The NIA contact is Ms. Georgeanne Patmios, 301-496-3138, patmiosg@nia.nih.gov. Challenge Topic 05-AG-102 calls for randomized controlled trials (RCTs) to evaluate the comparative effectiveness of competing interventions or modes of intervention delivery. A prime target for 05-AG-102 is the prevention of cognitive disability that results in health outcomes including improved quality of life, decreased mortality, morbidity, and disease progression, reduced medical care costs, and improvements in selected social and behavioral dimensions. The largest and most rigorous RCT ever conducted involving long-term follow-up was the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. Although all three ACTIVE cognitive training interventions (memory, reasoning, and speed of processing) were effective at improving their targeted abilities, the speed of processing group had the largest gains, with 87% of participants showing reliable improvement. We have also shown clinically significant effects of ACTIVE's speed of processing intervention (but no effects for the memory or reasoning interventions) on a variety of health outcomes, including: (1) a 3% reduction (p = .012) in predicted medical expenses; (2) a 38% reduction in the risk of global decline in health-related quality of life (HRQoL; p = .004); (3) a 30% reduction in the risk of worsening depressive symptoms (p = .012); (4) a 38% reduction in the risk of the onset of suspected clinical depression (p < .01); (5) improvements in self-rated health that translate to a 0.8% absolute reduction in the five-year mortality rate and a 10% relative mortality reduction (p < .05); and, (6) a 64% greater likelihood (p < .05) of meaningful improvements in internal locus of control. Despite the magnitude, diversity, and endurance of these effects of the speed of processing intervention, further research is needed before widespread dissemination is warranted for three reasons. First, ACTIVE relied on a no-contact control group rather than an attention control group, raising the potential for placebo effects. Second, although booster training was randomly offered to 60% of ACTIVE participants, it was offered conditional on completing > 8 of the 10 baseline training sessions, confounding booster effects with adherence effects. Third, a new, value-added version of the speed of processing software is now available that can be used on almost any home computer, and could thus dramatically reduce delivery costs and facilitate individual dosing and ongoing booster maintenance, but there is no published evidence that the value-added version is as effective as the original. Therefore, our specific aims are to overcome these limitations using an RCT with one-year follow- up that can be fully completed within the NIH Challenge Grant two-year period. We will randomize 900 participants aged 50 years old or older to three groups. Group G1 (N=400) will receive the value-added speed of processing intervention in 10 onsite sessions as in ACTIVE, with further randomization to one half (G1a) not receiving booster sessions and one half (G1b) receiving onsite booster sessions at 11-months. Group G2 (N=250) will be the attention control group and will receive 10 onsite sessions using a computerized cross-word puzzle program. Group G3 (N=250) will be shown how to operate the value- added speed of processing software on site, and will then be sent home to use it as often as they wish on their own personal computer. Our primary outcome measure is speed of processing, and we will use several reliable and valid instruments to provide a multidimensional assessment, including the Useful Field of View Test, the Symbol Digit Modalities Test, the Trail Making Test, the Controlled Oral Word Association Test, the Digit Vigilance Test, and the Stroop Color and Word Test. We have seven hypotheses for these primary outcome measures which will be tested using residualized change score multiple linear regression models for continuous outcomes, multiple logistic regression models for binary (threshold change) outcomes, and Poisson or negative binomial regression models for count measures. We will also evaluate the effects on several secondary outcomes, including HRQoL, healthcare utilization, depressive symptoms, functional abilities, perceived stress, self-efficacy, and sense of control. Finally, we will conduct stratified analysis among participants aged 50-64 years old, and separately among those aged 65 years or older in order to determine whether the effect size of the speed of processing intervention varies by age group. PUBLIC HEALH RELEVANCE: Although some degree of gradual cognitive decline is nearly universal and a normal part of the aging process, previous research by our group has shown that age-related cognitive decline is amenable to intervention. Building on speed of processing theory, we propose to extend and expand the findings from the NIH-funded, multi-site Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study by using a newly developed, value-added version of the speed of processing software that can be used on virtually any home computer without supervision. When shown to be at least as efficacious as the original, the value-added version of the speed of processing software will then be ready for widespread implementation among adults aged 50 years old or older to reduce and/or prevent the risk of disability driven by age-related cognitive decline.