Alzheimer’s disease (AD) is the most common neurodegenerative disorder in elderly subjects. Recent studies verified the effects of cognitive training combined with repetitive transcranial magnetic stimulation (rTMS-COG) in AD patients. Here, we analyzed neuropsychological and neurophysiological data, derived from electroencephalography (EEG), to evaluate the effects of a 6-week protocol of rTMS-COG in 72 AD. We designed a randomized, double-blind, sham-controlled trial to evaluate efficacy of rTMS on 6 brain regions obtained by an individual MRI combined with COG related to brain areas to stimulate (i.e., syntax and grammar tasks, comprehension of lexical meaning and categorization tasks, action naming, object naming, spatial memory, spatial attention). Patients underwent neuropsychological and EEG examination before (T₀), after treatment (T₁), and after 40 weeks (T₂), to evaluate the effects of rehabilitation therapy. “Small World” (SW) graph approach was introduced allowing us to model the architecture of brain connectivity in order to correlate it with cognitive improvements. We found that following 6 weeks of intensive daily treatment the immediate results showed an improvement in cognitive scales among AD patients. SW present no differences before and after the treatment, whereas a crucial SW modulation emerges at 40-week follow-up, emphasizing the importance of rTMS-COG rehabilitation treatment for AD. Additional results demonstrated that the delta and alpha1 SW seem to be diagnostic biomarkers of AD, whereas alpha2 SW might represent a prognostic biomarker of cognitive recovery. Derived EEG parameters can be awarded the role of diagnostic and predictive biomarkers of AD progression, and rTMS-COG can be regarded as a potentially useful treatment for AD.

阿尔茨海默病 (AD) 是老年受试者中最常见的神经退行性疾病。最近的研究证实了认知训练结合重复经颅磁刺激 (rTMS-COG) 对 AD 患者的影响。在这里，我们分析了源自脑电图 (EEG) 的神经心理学和神经生理学数据，以评估 72 AD 中 6 周 rTMS-COG 方案的效果。我们设计了一项随机、双盲、假对照试验，以评估 rTMS 对 6 个大脑区域的疗效，该试验通过单个 MRI 结合与大脑区域相关的 COG 进行刺激（即句法和语法任务、词汇含义的理解和分类）任务、动作命名、对象命名、空间记忆、空间注意）。患者之前接受过神经心理学和脑电图检查（T ₀)、治疗后 (T ₁ ) 和 40 周后 (T ₂)，以评估康复治疗的效果。引入了“小世界”（SW）图方法，使我们能够对大脑连接的架构进行建模，以便将其与认知改进相关联。我们发现，经过 6 周的每日强化治疗后，直接结果显示 AD 患者的认知量表有所改善。SW 在治疗前后没有差异，而关键的 SW 调节出现在 40 周的随访中，强调了 rTMS-COG 康复治疗对 AD 的重要性。其他结果表明，delta 和 alpha1 SW 似乎是 AD 的诊断生物标志物，而 alpha2 SW 可能代表认知恢复的预后生物标志物。衍生的脑电图参数可以被授予诊断和预测 AD 进展的生物标志物的作用，