Parkinson and Other Movement Disorders Center, Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Department of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Parkinson's Foundation Centre of Excellence, King's College Hospital, London, UK.
Parkinsonism Relat Disord. 2023 Jul;112:105385. doi: 10.1016/j.parkreldis.2023.105385. Epub 2023 Mar 29.
Cognitive impairment is common in Parkinson's disease (PD) and has a substantial impact on quality of life. Despite numerous trials targeting various PD features, we still lack effective treatments for cognition beyond cholinesterase inhibitors.
To identify the gaps in recent clinical trials with cognitive outcomes in PD and consider areas for improvement.
We examined recent clinical trials with cognitive outcomes in PD registered on ClinicalTrials.gov, excluding trials without cognitive outcomes, non-interventional studies, and in atypical Parkinsonian disorders. Included trials were categorized by treatment approach (investigational medicinal product, behavioral, physical activity, device-based). Details of trial design and outcomes were collected.
178 trials at different stages of trial completion were considered. 46 trials were completed, 25 had available results. Mean follow-up duration was 29.9 weeks. Most common cognitive measure was Montreal Cognitive Assessment. Most were performed in North America or Europe. Majority of the participants identified as non-Hispanic and White. Only eight trials showed improvement in cognition, none showed improvement beyond four months. These included trials of international medicinal products, cognitive and physical interventions and devices. GRADE certainty levels ranged from Moderate to Very Low. Only mevidalen had a Moderate certainty for potential clinical effectiveness.
Amongst a large number of trials for cognition in PD, only a small proportion were completed. Few showed significant improvement, with no proven long-lasting effects. Trial design, lack of enrichment for at-risk groups, short follow-up duration, insensitive outcome measures likely contribute to lack of detectable benefit and should be considered in future trials.
认知障碍在帕金森病（PD）中很常见，对生活质量有重大影响。尽管针对 PD 的各种特征进行了大量试验，但除了胆碱酯酶抑制剂之外，我们仍然缺乏有效的认知治疗方法。
确定 PD 认知结局的近期临床试验中的差距，并考虑改进的领域。
我们检查了在 ClinicalTrials.gov 上注册的具有 PD 认知结局的近期临床试验，排除了没有认知结局、非干预性研究和非典型帕金森病的试验。纳入的试验按治疗方法（研究药物、行为、身体活动、基于设备的方法）进行分类。收集了试验设计和结局的详细信息。
考虑了不同试验完成阶段的 178 项试验。有 46 项试验已经完成，25 项有可用结果。平均随访时间为 29.9 周。最常见的认知测量方法是蒙特利尔认知评估。大多数试验在美国或欧洲进行。大多数参与者为非西班牙裔和白人。只有八项试验显示认知能力有所改善，没有一项显示超过四个月的改善。这些试验包括国际药物、认知和身体干预以及设备的试验。GRADE 确定性水平从中等到非常低不等。只有 mevidalen 在潜在临床效果方面具有中等确定性。
在大量 PD 认知试验中，只有一小部分完成。很少有试验显示出显著的改善，没有经过证实的长期效果。试验设计、缺乏对高危人群的富集、随访时间短、敏感性差的结局测量可能导致无法检测到获益，应在未来的试验中考虑这些因素。
