Da Xiao, Hempel Evan, Brickman Adam M, Hajós Mihály, Kern Ralph, Cimenser Aylin
Cognito Therapeutics, Inc, Cambridge, MA, United States.
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.
Front Neurol. 2024 Oct 15;15:1452930. doi: 10.3389/fneur.2024.1452930. eCollection 2024.
To examine the impact of 40Hz gamma stimulation on the preservation of the corpus callosum, a critical structure for interhemispheric connectivity, in people with mild cognitive impairment or Alzheimer's disease.
OVERTURE (NCT03556280) participants were randomized 2:1 (Active:Sham) to receive daily, 1-h, 40Hz gamma sensory stimulation or sham treatment for 6 months. Structural magnetic resonance imaging data were analyzed to assess changes in corpus callosum area ( = 50; 33 for active, 17 for sham). Bayesian linear mixed-effects modeling was used to assess differences in longitudinal changes of corpus callosum area between the two treatment groups.
All observed differences in corpus callosum area favored the active treatment group. Differences were observed in the total corpus callosum area (2.28 ± 0.87%, < 0.02) and its subregions, including genu/rostrum (2.36 ± 0.90%, < 0.02), anterior-body (2.64 ± 1.26%, < 0.04), mid-body (2.79 ± 1.18%, < 0.03), posterior-body (2.87 ± 1.41%, < 0.05), and splenium (1.58 ± 0.73%, < 0.04). Total corpus callosum area and some of the sub-regional differences, such as genu/rostrum and splenium, were observed as early as 3 months after commencement of treatment.
The structural magnetic resonance imaging results from the OVERTURE Phase 2 study suggest that 6 months of non-invasive 40Hz stimulation reduces the rate of atrophy of the corpus callosum in individuals with Alzheimer's disease. The preservation of structural integrity in the corpus callosum, crucial for interhemispheric communication and cognitive function, may be achievable through this non-invasive approach, potentially providing a promising disease-modifying alternative in Alzheimer's disease management.
研究40赫兹伽马刺激对轻度认知障碍或阿尔茨海默病患者胼胝体（半球间连接的关键结构）保存情况的影响。
“序曲”（OVERTURE，NCT03556280）研究的参与者按2:1比例随机分组（主动治疗组：假治疗组），接受为期6个月的每日1小时40赫兹伽马感觉刺激或假治疗。分析结构磁共振成像数据，以评估胼胝体面积的变化（n = 50；主动治疗组33例，假治疗组17例）。采用贝叶斯线性混合效应模型评估两个治疗组之间胼胝体面积纵向变化的差异。
胼胝体面积观察到的所有差异均有利于主动治疗组。在胼胝体总面积（2.28 ± 0.87%，P < 0.02）及其子区域观察到差异，包括膝部/嘴部（2.36 ± 0.90%，P < 0.02）、前体部（2.64 ± 1.26%，P < 0.04）、中部（2.79 ± 1.18%，P < 0.03）、后部（2.87 ± 1.41%，P < 0.05）和压部（1.58 ± 0.73%，P < 0.04）。胼胝体总面积以及一些子区域差异，如膝部/嘴部和压部差异，在治疗开始后3个月就已观察到。
“序曲”2期研究中的结构磁共振成像结果表明，6个月的非侵入性40赫兹刺激可降低阿尔茨海默病患者胼胝体的萎缩率。对于半球间交流和认知功能至关重要的胼胝体结构完整性的保存，可能通过这种非侵入性方法实现，这可能为阿尔茨海默病管理提供一种有前景的疾病修饰替代方案。
