Cognitive Complaints in a Diverse Cohort of Elders: Novel Assessment Approaches

描述(由申请人提供)：记忆丧失的主观感觉在老年人中非常常见，尽管用传统的神经心理学工具评估，认知抱怨和表现之间没有直接的关系。我们已经确定了一组没有抑郁、健康的老年人，尽管在广泛的神经心理测试中功能完整(称为认知抱怨，CC组)，但仍有显著的认知抱怨(特别是涉及记忆)。这些人的大脑结构变化介于遗忘性轻度认知障碍(MCI)和正常老年人之间，可能代表了MCI前期人群。因此，在其他健康、非抑郁的老年人中，认知主诉可能表明潜在的神经退行性变化，这可能提供比MCI更早的治疗机会。然而，要实现这一潜力，需要更好地理解自我评估记忆与实际表现之间的关系，以及影响这种关系的因素。我们的主要目标是使用新的范式来测试关于认知抱怨的性质和临床意义的假设，在人口统计学上不同的大约250名患有不同程度的认知抱怨和损害的老年人中。我们认为，认知主诉反映了常规工具不易发现的细微异常，而使用传统情景记忆之外的范式开发的任务可能提供更敏感的标准来测试主观记忆和客观记忆之间的关系。我们将招募符合纳入标准的非抑郁、非痴呆的老年人，并使用提案中描述的程序将他们归类为健康对照、CC或MCI。我们预测，神经心理正常、有明显认知主诉的老年人，但不是没有主诉的老年人，将表现出：(1)尽管在常规工具上表现完好，但在前瞻性和程序性元记忆任务上表现出轻微的成绩缺陷；(2)记忆自我效能感降低，记忆策略和补偿行为的使用减少；以及(3)随着时间的推移，转换为MCI的风险增加。我们的长期目标是评估认知主诉的诊断和预测效用，并确定最能预测MCI前期到MCI和最终痴呆症进展的变量。我们还希望在未来扩大队列，并对MCI前期患者实施认知干预，针对在拟议研究中被发现相关的和潜在可修改的行为和信念，例如加强记忆策略和自我效能的使用。这项拟议的研究将具有以社区为基础的样本、纵向设计和心理测量方法评估认知投诉的优势。NIH对这一提议的支持将为申请人提供过渡到独立调查人员所需的经验。重要的是，这些发现将促进对记忆自我评估和痴呆症发病前认知变化的科学理解，对早期诊断和临床护理具有重要意义。 公共卫生相关性：阿尔茨海默病(AD)是一个严重影响患者、他们的家庭和社会的重大全球公共卫生问题；在AD的早期表现中了解正常和异常的记忆过程是一个关键的研究重点，有助于检测痴呆前期状况。这项拟议的研究将促进对记忆自我评估和AD发病前认知变化的基本科学理解，对早期诊断、临床护理和干预具有重要意义。此外，这项研究将通过增加少数人获得研究的机会，并提高区分进行性认知能力下降的高危人群和可以放心和跟踪的“担心良好”的人的能力，来满足重要的公共卫生需求。

DESCRIPTION (provided by applicant): Subjective perception of memory loss is very common in older adults, though there is no straightforward relationship between cognitive complaints and performance as assessed with conventional neuropsychological instruments. We have identified a group of nondepressed, healthy older adults with significant cognitive complaints (particularly involving memory) despite intact functioning on extensive neuropsychological testing (referred to as the Cognitive Complaint, CC, group). These individuals show structural brain changes intermediate between those seen in amnestic mild cognitive impairment (MCI) and normal elders and may represent a "pre-MCI" population. Thus, cognitive complaints in otherwise healthy, nondepressed older adults may indicate underlying neurodegenerative changes that could provide an earlier therapeutic opportunity than MCI. The realization of this potential, however, will require an improved understanding of the relationship between self-appraised memory and actual performance, as well as the factors that influence this relationship. Our main goal is to use novel paradigms to test hypotheses regarding the nature and clinical significance of cognitive complaints in a demographically diverse group of approximately 250 older adults with varying degrees of cognitive complaints and impairment. We propose that cognitive complaints reflect subtle abnormalities not readily detected by conventional tools, and that tasks developed using paradigms other than traditional episodic memory may provide more sensitive criteria by which to test the relationship between subjective and objective memory. We will enroll nondepressed, nondemented older adults meeting inclusion criteria and classify them as healthy control, CC, or MCI using the procedures described in the proposal. We predict that neuropsychologically intact older adults with marked cognitive complaints, but not those without complaints, will show: (1) mild performance deficits on prospective and procedural metamemory tasks despite intact performance on conventional tools; (2) lower memory self-efficacy and reduced use of mnemonic strategies and compensatory behaviors; and (3) increased risk of conversion to MCI over time. Our long-term goals are to evaluate the diagnostic and predictive utility of cognitive complaints and identify variables that best predict progression from pre-MCI to MCI and eventually dementia. We also hope to expand the cohort in the future and implement a cognitive intervention for pre-MCI that targets behaviors and beliefs that were found to be relevant in the proposed study and that are potentially modifiable, such as enhancing the use of memory strategies and self-efficacy. The proposed study will have the advantages of a community-based sample, longitudinal design, and psychometric approach to the assessment of cognitive complaints. NIH support of this proposal will provide the applicant with the experience necessary to transition to an independent investigator. Importantly, findings will advance scientific understanding of memory self-appraisals and the cognitive changes that precede the onset of dementia, with important implications for early diagnosis and clinical care. PUBLIC HEALTH RELEVANCE: Alzheimer's disease (AD) is a major global public health problem that seriously impacts patients, their families, and society; an understanding of normal and abnormal memory processes in the early presentation of AD is a critical research priority that will facilitate detection of predementia conditions. The proposed study will advance basic scientific understanding of memory self-appraisals and the cognitive changes that precede the onset of AD, with significant implications for early diagnosis, clinical care, and intervention. Additionally, this study will meet important public health needs by increasing minority access to research and improving the ability to differentiate individuals at high risk for progressive cognitive decline from the "worried well," who can be reassured and followed.