Background:Frontotemporal dementia (FTD) is a presenile neurodegenerative disease for which there is no effective pharmacological treatment. Recently, a link has been proposed between neuroinflammation and FTD. Objective:Here, we aim to investigate the effects of palmitoylethanolamide (PEA) combined with luteoline (PEA-LUT), an endocannabinoid with anti-inflammatory and neuroprotective effects, on behavior, cognition, and cortical activity in a sample of FTD patients. Methods:Seventeen patients with a diagnosis of probable FTD were enrolled. Cognitive and neurophysiological evaluations were performed at baseline and after 4 weeks of PEA-LUT 700 mg×2/day. Cognitive effects were assessed by Neuropsychiatric Inventory (NPI), Mini-Mental State Examination, Frontal Assessment Battery (FAB), Screening for Aphasia in Neurodegeneration, Activities of Daily Living-Instrumental Activities of Daily Living, and Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating scale. To investigate in vivo neurophysiological effects of PEA-LUT, we used repetitive and paired-pulse transcranial magnetic stimulation (TMS) protocols assessing LTP-like cortical plasticity, short-interval intracortical inhibition, long-interval intracortical inhibition (LICI), and short-latency afferent inhibition. Moreover, we used TMS combined with EEG to evaluate the effects on frontal lobe cortical oscillatory activity. Results:Treatment with PEA-LUT was associated with an improvement in NPI and FAB scores. Neurophysiological evaluation showed a restoration of LICI, in particular at ISI 100 ms, suggesting a modulation of GABA(B) activity. TMS-EEG showed a remarkable increase of TMS-evoked frontal lobe activity and of high-frequency oscillations in the beta/gamma range. Conclusion:PEA-LUT could reduce behavioral disturbances and improve frontal lobe functions in FTD patients through the modulation of cortical oscillatory activity and GABA(B)ergic transmission.

中文翻译：

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棕榈酰乙醇酰胺联合叶黄素对额颞痴呆患者额叶功能，高频振荡和GABA能传递的影响。

背景：额颞叶痴呆（FTD）是一种老年性神经退行性疾病，目前尚无有效的药物治疗方法。近来，已经提出了神经炎症与FTD之间的联系。目的：在这里，我们旨在研究棕榈酰乙醇酰胺（PEA）联合具有抗炎和神经保护作用的内源性大麻素卢替林（PEA-LUT）对FTD患者的行为，认知和皮层活动的影响。方法：纳入17名诊断为FTD可能的患者。PEA-LUT 700 mg×2 /天的基线和4周后进行认知和神经生理学评估。通过神经精神病学调查表（NPI），小精神状态检查，额叶评估电池（FAB），神经退行性失语症筛查，日常生活活动-日常生活中的仪器活动以及额颞叶变性变性临床痴呆评定量表。为了研究PEA-LUT在体内的神经生理作用，我们使用重复和成对脉冲经颅磁刺激（TMS）方案评估LTP样皮质可塑性，短间隔皮质内抑制，长间隔皮质内抑制（LICI）和短间隔皮质内抑制潜伏期传入抑制。此外，我们使用TMS结合脑电图评估对额叶皮质振荡活动的影响。结果：用PEA-LUT治疗与NPI和FAB得分的改善有关。神经生理学评估显示LICI的恢复，特别是在ISI 100 ms时，表明GABA（B）活性得到调节。TMS-EEG显示，TMS诱发的额叶活性和β/γ范围内的高频振荡均显着增加。结论：PEA-LUT可通过调节皮层振荡活动和GABA（B）能传递来减少FTD患者的行为障碍并改善额叶功能。