Effects of Palmitoylethanolamide Combined with Luteoline on Frontal Lobe Functions, High Frequency Oscillations, and GABAergic Transmission in Patients with Frontotemporal Dementia

• Published in: Journal of Alzheimer's disease 2020-01, Vol.76 (4), p.1297-1308
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Activities of daily living; Alzheimer's disease; Aphasia; Cognition; Cognitive ability; Degeneration; Dementia; Dementia disorders; Drug therapy; EEG; Evaluation; Frontal lobe; Frontotemporal dementia; Health services; In vivo methods and tests; Inflammation; Latency; Magnetic fields; Modulation; Neurodegeneration; Neurodegenerative diseases; Neuroplasticity; Neuroprotection; Oscillations; Palmitoylethanolamide; Patients; Restoration; Sensory neurons; Transcranial magnetic stimulation; γ-Aminobutyric acid
• ISSN: 1387-2877; 1875-8908
• DOI: 10.3233/JAD-200426

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.