Abstract

Background:

The progressive aging of the population will dramatically increase the burden of dementia related to Alzheimer’s disease (AD) and other neurodegenerative disorders in the future. Because of the absence of drugs that can modify the neuropathological substrate of AD, research is focusing on the application of preemptive and disease-modifying strategies in the pre-symptomatic period of the disease. In this perspective, the identification of people with cognitive frailty (CF), i.e., those individuals with higher risk of developing dementia, on solid pathophysiological bases and with clear operational clinical criteria is of paramount importance.

Objective/Methods:

This hypothesis paper reviews the current definitions of CF, presents and discusses some of their limitations, and proposes a framework for updating and improving the conceptual and operational definition of the CF construct.

Results:

The potential for reversibility of CF should be supported by the assessment of amyloid, tau, and neuronal damage biomarkers, especially in younger patients. Physical and cognitive components of frailty should be considered as separate entities, instead of part of a single macro-phenotype. CF should not be limited to the geriatric population, because trajectories of amyloid accumulation are supposed to start earlier than 65 years in AD. Operational criteria are needed to standardize assessment of CF.

Conclusion:

Based on the limitations of current CF definitions, we propose a revised one according to a multidimensional subtyping. This new definition might help stratifying CF patients for future trials to explore new lifestyle interventions or disease-modifying pharmacological strategies for AD and dementia.

中文翻译：

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重新定义认知弱点。

摘要

背景：

人口的逐步老化将在未来极大地增加与阿尔茨海默氏病（AD）和其他神经退行性疾病有关的痴呆症负担。由于缺乏可以改变AD神经病理学底物的药物，因此研究集中在疾病的症状前期先发性疾病和疾病改变策略的应用。从这个角度来看，识别具有脆弱性的人，即具有坚实的病理生理学基础并具有明确的临床操作标准的罹患痴呆症的风险较高的人至关重要。

目的/方法：

该假设文件回顾了CF的当前定义，提出并讨论了它们的局限性，并提出了更新和改进CF构造的概念和操作定义的框架。

结果：

CF的可逆性潜力应通过淀粉样蛋白，tau蛋白和神经元损伤生物标志物的评估来支持，尤其是在年轻患者中。脆弱的身体和认知组成部分应被视为独立的实体，而不是单个宏观表型的一部分。CF不应仅限于老年人群，因为淀粉样蛋白积累的轨迹应该早于AD的65岁开始。需要操作标准来标准化CF评估。

结论：

基于当前CF定义的局限性，我们根据多维子类型提出了一种修订的定义。这个新定义可能有助于对CF患者进行分层，以用于将来的试验，以探索针对AD和痴呆症的新的生活方式干预措施或改变疾病的药理策略。