Wang Laura A, Goldberg Terry E, Harvey Philip D, Hanson Angela J, Motter Jeffrey, Andrews Howard, Qian Min, Zhang Renjie, Janis Meaghan, Doraiswamy P Murali, Devanand Davangere P
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, USA.
Area Brain Aging and Mental Health, New York State Psychiatric Institute, New York, USA.
Int J Clin Trials. 2025 Apr-Jun;12(2):111-120. doi: 10.18203/2349-3259.ijct20251032. Epub 2025 Apr 11.
Cognitive training represents an important potential therapeutic strategy for mild cognitive impairment (MCI). In our recently completed trial, crossword puzzles were superior to computerized cognitive training on Alzheimer's disease assessment scale-cognitive subscale-11 (ADAS-Cog11) and function, correlating with decreased brain atrophy over 78 weeks.
COGIT-2 is a 78-week, multicenter, clinical trial comparing home-based, high-dose crosswords (4 puzzles per week) to low-dose crosswords (1 puzzle per week) and a health education control group in 240 MCI subjects. Crossword puzzles, administered by the CogniFit research platform, have been designed to have a moderate level of difficulty.
The primary outcome is change in ADAS-Cog14 and the main secondary outcome is change in informant reported daily functioning. Additional outcomes include changes in magnetic resonance imaging (MRI) hippocampal volume and cortical thickness as well as changes in plasma neurofilament light and plasma pTau217.
If the efficacy of computerized crossword puzzle training is confirmed in COGIT-2, crosswords training could become a low-cost, home-based, scalable, cognitive enhancement tool for people at risk for Alzheimer's disease. The dose comparison will provide useful information on the preferred frequency of crossword puzzle training.
Trial registration number ClinicalTrials.gov identifier (NCT06601933).
认知训练是治疗轻度认知障碍（MCI）的一项重要潜在策略。在我们最近完成的试验中，填字游戏在阿尔茨海默病评估量表-认知分量表-11（ADAS-Cog11）及功能方面优于计算机化认知训练，且与78周内脑萎缩减少相关。
COGIT-2是一项为期78周的多中心临床试验，在240名MCI受试者中，将居家高剂量填字游戏（每周4个谜题）与低剂量填字游戏（每周1个谜题）及一个健康教育对照组进行比较。由CogniFit研究平台提供的填字游戏设计为中等难度水平。
主要结局指标是ADAS-Cog14的变化，主要次要结局指标是 informant报告的日常功能变化。其他结局指标包括磁共振成像（MRI）海马体积和皮质厚度的变化，以及血浆神经丝轻链和血浆pTau217的变化。
如果计算机化填字游戏训练的疗效在COGIT-2中得到证实，填字游戏训练可能会成为一种低成本、居家、可扩展的认知增强工具，用于有患阿尔茨海默病风险的人群。剂量比较将为填字游戏训练的最佳频率提供有用信息。
试验注册号ClinicalTrials.gov标识符（NCT06601933）。
