Assogna Martina, Casula Elias Paolo, Borghi Ilaria, Bonnì Sonia, Samà Domenico, Motta Caterina, Di Lorenzo Francesco, D'Acunto Alessia, Porrazzini Francesco, Minei Marilena, Caltagirone Carlo, Martorana Alessandro, Koch Giacomo
Santa Lucia Foundation, IRCCS, Rome, Italy.
Tor Vergata Policlinic, Rome, Italy.
J Alzheimers Dis. 2020;76(4):1297-1308. doi: 10.3233/JAD-200426.
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.
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.
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.
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.
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.
额颞叶痴呆（FTD）是一种早老性神经退行性疾病，目前尚无有效的药物治疗方法。最近，有人提出神经炎症与FTD之间存在联系。
在此，我们旨在研究棕榈酰乙醇胺（PEA）与木犀草素（PEA-LUT，一种具有抗炎和神经保护作用的内源性大麻素）联合使用对FTD患者样本的行为、认知和皮层活动的影响。
招募了17名诊断为可能患有FTD的患者。在基线时以及服用700mg×2/天的PEA-LUT 4周后进行认知和神经生理学评估。通过神经精神科问卷（NPI）、简易精神状态检查表、额叶评估量表（FAB）、神经退行性疾病失语症筛查、日常生活活动-工具性日常生活活动以及额颞叶变性改良临床痴呆评定量表评估认知效果。为了研究PEA-LUT的体内神经生理学效应，我们使用重复和配对脉冲经颅磁刺激（TMS）方案来评估类似长时程增强的皮层可塑性、短间隔皮层内抑制、长间隔皮层内抑制（LICI）和短潜伏期传入抑制。此外，我们使用TMS结合脑电图来评估对额叶皮层振荡活动的影响。
PEA-LUT治疗与NPI和FAB评分的改善相关。神经生理学评估显示LICI恢复，特别是在间隔时间100ms时，提示GABA(B)活性受到调节。TMS-脑电图显示TMS诱发的额叶活动以及β/γ范围内的高频振荡显著增加。
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。
