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N-Pep-12 supplementation after ischemic stroke positively impacts frequency domain QEEG

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Abstract

Background

N-Pep-12 is a dietary supplement with neuroprotective and pro-cognitive effects, as shown in experimental models and clinical studies on patients after ischemic stroke. We tested the hypothesis that N-Pep-12 influences quantitative electroencephalography (QEEG) parameters in patients with subacute to chronic supratentorial ischemic lesions.

Methods

We performed secondary data analysis on an exploratory clinical trial (ISRCTN10702895), assessing the efficacy and safety of 90 days of once-daily treatment with 90 mg N-Pep-12 on neurocognitive function and neurorecovery outcome in patients with post-stroke cognitive impairment against a control group. All participants performed two 32-channel QEEG in resting and active states at baseline (30–120 days after stroke) and 90 days later. Power spectral density on the alpha, beta, theta, delta frequency bands, delta/alpha power ratio (DAR), and (delta+theta)/(alpha+beta) ratio (DTABR) were computed and compared across study groups using means comparison and descriptive methods. Secondarily, associations between QEEG parameters and available neuropsychological tests were explored.

Results

Our analysis showed a statistically significant main effect of EEG segments (p<0.001) in alpha, beta, delta, theta, DA, and DTAB power spectral density. An interaction effect between EEG segments and time was noticed in the alpha power. There was a significant difference in theta spectral power between patients with N-Pep-12 supplementation versus placebo at 0.05 alpha level (p=0.023), independent of time points.

Conclusion

A 90-day, 90 mg daily administration of N-Pep-12 had significant impact on some QEEG indicators in patients after supratentorial ischemic stroke, confirming possible enhancement of post-stroke neurorecovery. Further research is needed to consolidate our findings.

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References

  1. Cucchiara B, George DK, Kasner SE, Knutsson M, Denison H, Ladenvall P, Amarenco P, Johnston SC (2019) Disability after minor stroke and TIA: a secondary analysis of the SOCRATES trial. Neurology 93:e708–e716. https://doi.org/10.1212/WNL.0000000000007936

    Article  PubMed  Google Scholar 

  2. Shavelle RM, Brooks JC, Strauss DJ, Turner-Stokes L (2019) Life expectancy after stroke based on age, sex, and rankin grade of disability: a synthesis. J Stroke Cerebrovasc Dis 28:104450. https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104450

    Article  PubMed  Google Scholar 

  3. Gorelick PB (2019) The global burden of stroke: persistent and disabling. The Lancet Neurology 18:417–418. https://doi.org/10.1016/S1474-4422(19)30030-4

    Article  PubMed  Google Scholar 

  4. Mijajlović MD, Pavlović A, Brainin M, Heiss WD, Quinn TJ, Ihle-Hansen HB, Hermann DM, Assayag EB, Richard E, Thiel A, Kliper E, Shin YI, Kim YH, Choi SH, Jung S, Lee YB, Sinanović O, Levine DA, Schlesinger I, Mead G, Milošević V, Leys D, Hagberg G, Ursin MH, Teuschl Y, Prokopenko S, Mozheyko E, Bezdenezhnykh A, Matz K, Aleksić V, Muresanu DF, Korczyn AD, Bornstein NM (2017) Post-stroke dementia - a comprehensive review. BMC Med 15:11–11. https://doi.org/10.1186/s12916-017-0779-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. O’Brien JT, Erkinjuntti T, Reisberg B et al (2003) Vascular cognitive impairment. Lancet Neurol 2:89–98. https://doi.org/10.1016/s1474-4422(03)00305-3

    Article  PubMed  Google Scholar 

  6. Graff-Radford J (2019) Vascular Cognitive Impairment. Continuum (Minneap Minn) 25:147–164. https://doi.org/10.1212/CON.0000000000000684

    Article  Google Scholar 

  7. Petrovic J, Milosevic V, Zivkovic M, Stojanov D, Milojkovic O, Kalauzi A, Saponjic J (2017) Slower EEG alpha generation, synchronization and “flow”-possible biomarkers of cognitive impairment and neuropathology of minor stroke. PeerJ 5:e3839. https://doi.org/10.7717/peerj.3839

    Article  PubMed  PubMed Central  Google Scholar 

  8. Foreman B, Claassen J (2012) Quantitative EEG for the detection of brain ischemia. Crit Care 16:216. https://doi.org/10.1186/cc11230

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bentes C, Peralta AR, Viana P, Martins H, Morgado C, Casimiro C, Franco AC, Fonseca AC, Geraldes R, Canhão P, Pinho e Melo T, Paiva T, Ferro JM (2018) Quantitative EEG and functional outcome following acute ischemic stroke. Clin Neurophysiol 129:1680–1687. https://doi.org/10.1016/j.clinph.2018.05.021

    Article  PubMed  Google Scholar 

  10. Hernández-Hernández EM, Caporal Hernandez K, Vázquez-Roque RA, Díaz A, de la Cruz F, Florán B, Flores G (2018) The neuropeptide-12 improves recognition memory and neuronal plasticity of the limbic system in old rats. Synapse 72:e22036. https://doi.org/10.1002/syn.22036

    Article  PubMed  CAS  Google Scholar 

  11. Hutter-Paier B, Reininger-Gutmann B, Wronski R, Doppler E, Moessler H (2015) Long-term treatment of aged Long Evans rats with a dietary supplement containing neuroprotective peptides (N-PEP-12) to prevent brain aging: effects of three months daily treatment by oral gavage. J Med Life 8:207–212

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Windisch M, Hutter-Paier B, Grygar E, Doppler E, Moessler H (2005) N-PEP-12 – a novel peptide compound that protects cortical neurons in culture against different age and disease associated lesions. J Neural Transm 112:1331–1343. https://doi.org/10.1007/s00702-005-0283-7

    Article  PubMed  CAS  Google Scholar 

  13. Alvarez XA, Corzo L, Laredo M et al (2005) Neuropeptide dietary supplement N-PEP-12 enhances cognitive function and activates brain bioelectrical activity in healthy elderly subjects. Methods Find Exp Clin Pharmacol 27:483–487. https://doi.org/10.1358/mf.2005.27.7.914776

    Article  PubMed  CAS  Google Scholar 

  14. Balea M, Birle C, Costin C, Marton J, Muresanu IA, Jemna N, Popa LL, Slavoaca D, Rosu OV, Stan A, Vacaras V, Strilciuc S, Muresanu DF (2020) Effects of N-Pep-12 dietary supplementation on neurorecovery after ischemic stroke. Neurol Sci 42:2031–2037. https://doi.org/10.1007/s10072-020-04707-9

    Article  PubMed  Google Scholar 

  15. Crook TH, Ferris SH, Alvarez XA, Laredo M, Moessler H (2005) Effects of N-PEP-12 on memory among older adults. Int Clin Psychopharmacol 20:97–100. https://doi.org/10.1097/00004850-200503000-00006

    Article  PubMed  Google Scholar 

  16. Friedrich S, Konietschke F, Pauly M (2019) Resampling-based analysis of multivariate data and repeated measures designs with the R package MANOVA.RM. The R Journal 11:380–400

    Article  Google Scholar 

  17. Aminov A, Rogers JM, Johnstone SJ, Middleton S, Wilson PH (2017) Acute single channel EEG predictors of cognitive function after stroke. PLoS One 12:e0185841. https://doi.org/10.1371/journal.pone.0185841

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Cuspineda E, Machado C, Galán L, Aubert E, Alvarez MA, Llopis F, Portela L, García M, Manero JM, Ávila Y (2007) QEEG prognostic value in acute stroke. Clin EEG Neurosci 38:155–160. https://doi.org/10.1177/155005940703800312

    Article  PubMed  CAS  Google Scholar 

  19. Ghorbani M, Clark CCT (2021) Brain function during central fatigue induced by intermittent high-intensity cycling. Neurol Sci. https://doi.org/10.1007/s10072-020-04965-7

  20. Finnigan S, van Putten MJAM (2013) EEG in ischaemic stroke: quantitative EEG can uniquely inform (sub-)acute prognoses and clinical management. Clin Neurophysiol 124:10–19. https://doi.org/10.1016/j.clinph.2012.07.003

    Article  PubMed  Google Scholar 

  21. Schleiger (2017) Poststroke QEEG informs early prognostication of cognitive impairment. Psychophysiology 54(2):301–309. https://doi.org/10.1111/psyp.12785

    Article  PubMed  Google Scholar 

  22. Schleiger E, Sheikh N, Rowland T, Wong A, Read S, Finnigan S (2014) Frontal EEG delta/alpha ratio and screening for post-stroke cognitive deficits: the power of four electrodes. Int J Psychophysiol 94:19–24. https://doi.org/10.1016/j.ijpsycho.2014.06.012

    Article  PubMed  Google Scholar 

  23. Muresanu DF, Strilciuc S, Stan A (2019) Current drug treatment of acute ischemic stroke: challenges and opportunities. CNS Drugs 33:841–847. https://doi.org/10.1007/s40263-019-00663-x

    Article  PubMed  CAS  Google Scholar 

  24. Bernhardt J, Hayward KS, Kwakkel G, Ward NS, Wolf SL, Borschmann K, Krakauer JW, Boyd LA, Carmichael ST, Corbett D, Cramer SC (2017) Agreed definitions and a shared vision for new standards in stroke recovery research: The Stroke Recovery and Rehabilitation Roundtable taskforce. Int J Stroke 12:444–450. https://doi.org/10.1177/1747493017711816

    Article  PubMed  Google Scholar 

  25. Seleznov I, Zyma I, Kiyono K, Tukaev S, Popov A, Chernykh M, Shpenkov O (2019) Detrended fluctuation, coherence, and spectral power analysis of activation rearrangement in EEG dynamics during cognitive workload. Front Hum Neurosci 13:270. https://doi.org/10.3389/fnhum.2019.00270

    Article  PubMed  PubMed Central  Google Scholar 

  26. Crk (2014) Toward using alpha and theta brain waves to quantify programmer expertise 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society 5373-5376 https://doi.org/10.1109/EMBC.2014.6944840

  27. Mitchell DJ, McNaughton N, Flanagan D, Kirk IJ (2008) Frontal-midline theta from the perspective of hippocampal “theta.”. Prog Neurobiol 86:156–185. https://doi.org/10.1016/j.pneurobio.2008.09.005

    Article  PubMed  Google Scholar 

  28. Wichniak (2014) Electroencephalographic theta activity and cognition in schizophrenia: preliminary results

  29. Ozgören M, Başar-Eroğlu C, Başar E (2005) Beta oscillations in face recognition. Int J Psychophysiol 55:51–59. https://doi.org/10.1016/j.ijpsycho.2004.06.005

    Article  PubMed  Google Scholar 

  30. Schneider JM, Abel AD, Ogiela DA, Middleton AE, Maguire MJ (2016) Developmental differences in beta and theta power during sentence processing. Dev Cogn Neurosci 19:19–30. https://doi.org/10.1016/j.dcn.2016.01.001

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bastiaansen MCM, Oostenveld R, Jensen O, Hagoort P (2008) I see what you mean: theta power increases are involved in the retrieval of lexical semantic information. Brain Lang 106:15–28. https://doi.org/10.1016/j.bandl.2007.10.006

    Article  PubMed  Google Scholar 

  32. Demiralp T, Başar E (1992) Theta rhythmicities following expected visual and auditory targets. Int J Psychophysiol 13:147–160. https://doi.org/10.1016/0167-8760(92)90054-f

    Article  PubMed  CAS  Google Scholar 

  33. Tolonen U, Sulg IA (1981) Comparison of quantitative EEG parameters from four different analysis techniques in evaluation of relationships between EEG and CBF in brain infarction. Electroencephalogr Clin Neurophysiol 51:177–185. https://doi.org/10.1016/0013-4694(81)90007-9

    Article  PubMed  CAS  Google Scholar 

  34. Jordan KG (2004) Emergency EEG and continuous EEG monitoring in acute ischemic stroke. J Clin Neurophysiol 21:341–352

    PubMed  Google Scholar 

  35. Gotman J, Skuce D, Thompson C (1973) Clinical applications of spectral analysis and extraction of features from electroencephalograms with slow waves in adult patients. Electroencephalogr Clin Neurophysiol 35(3):225–235. https://doi.org/10.1016/0013-4694(73)90233-2

    Article  PubMed  CAS  Google Scholar 

  36. Muresanu DF, Alvarez XA (2008) A pilot study to evaluate the effects of Cerebrolysin on cognition and qEEG in vascular dementia: Cognitive improvement correlates with qEEG acceleration. J Neurol Sci 267(1-2):112–119. https://doi.org/10.1016/j.jns.2007.10.016

    Article  PubMed  CAS  Google Scholar 

  37. Muresanu DF (2010) Persistence of the effects of Cerebrolysin on cognition and qEEG slowing in vascular dementia patients: Results of a 3-month extension study. J Neurol Sci 299(1-2):179–183. https://doi.org/10.1016/j.jns.2010.08.040

    Article  PubMed  CAS  Google Scholar 

  38. Iyer KK (2017) Effective assessments of electroencephalography during stroke recovery: contemporary approaches and considerations. J Neurophysiol 118:2521–2525. https://doi.org/10.1152/jn.00206.2017

    Article  PubMed  PubMed Central  Google Scholar 

  39. Klimesch W (2012) α-band oscillations, attention, and controlled access to stored information. Trends Cogn Sci 16:606–617. https://doi.org/10.1016/j.tics.2012.10.007

    Article  PubMed  PubMed Central  Google Scholar 

  40. Hurford R, Charidimou A, Fox Z, Cipolotti L, Werring DJ (2013) Domain-specific trends in cognitive impairment after acute ischaemic stroke. J Neurol 260:237–241. https://doi.org/10.1007/s00415-012-6625-0

    Article  PubMed  Google Scholar 

  41. Finnigan S, Robertson IH (2011) Resting EEG theta power correlates with cognitive performance in healthy older adults. Psychophysiology 48:1083–1087. https://doi.org/10.1111/j.1469-8986.2010.01173.x

    Article  PubMed  Google Scholar 

  42. Cummins TDR, Finnigan S (2007) Theta power is reduced in healthy cognitive aging. Int J Psychophysiol 66:10–17. https://doi.org/10.1016/j.ijpsycho.2007.05.008

    Article  PubMed  Google Scholar 

  43. Lithfous S, Tromp D, Dufour A, Pebayle T, Goutagny R, Després O (2015) Decreased theta power at encoding and cognitive mapping deficits in elderly individuals during a spatial memory task. Neurobiol Aging 36:2821–2829. https://doi.org/10.1016/j.neurobiolaging.2015.07.007

    Article  PubMed  Google Scholar 

  44. Kardos Z, Tóth B, Boha R, File B, Molnár M (2014) Age-related changes of frontal-midline theta is predictive of efficient memory maintenance. Neuroscience 273:152–162. https://doi.org/10.1016/j.neuroscience.2014.04.071

    Article  PubMed  CAS  Google Scholar 

  45. Tóth B, Kardos Z, File B, Boha R, Stam CJ, Molnár M (2014) Frontal midline theta connectivity is related to efficiency of WM maintenance and is affected by aging. Neurobiol Learn Mem 114:58–69. https://doi.org/10.1016/j.nlm.2014.04.009

    Article  PubMed  Google Scholar 

  46. Hughes LE, Rittman T, Robbins TW, Rowe JB (2018) Reorganization of cortical oscillatory dynamics underlying disinhibition in frontotemporal dementia. Brain 141:2486–2499. https://doi.org/10.1093/brain/awy176

    Article  PubMed  PubMed Central  Google Scholar 

  47. Musaeus CS, Engedal K, Høgh P, Jelic V, Mørup M, Naik M, Oeksengaard AR, Snaedal J, Wahlund LO, Waldemar G, Andersen BB (2018) EEG Theta Power Is an Early Marker of Cognitive Decline in Dementia due to Alzheimer’s Disease. J Alzheimers Dis 64:1359–1371. https://doi.org/10.3233/JAD-180300

    Article  PubMed  Google Scholar 

  48. Song Y, Zang D-W, Jin Y-Y, Wang ZJ, Ni HY, Yin JZ, Ji DX (2015) Background rhythm frequency and theta power of quantitative EEG analysis: predictive biomarkers for cognitive impairment post-cerebral infarcts. Clin EEG Neurosci 46:142–146. https://doi.org/10.1177/1550059413517492

    Article  PubMed  Google Scholar 

  49. Finnigan S, Wong A, Read S (2016) Defining abnormal slow EEG activity in acute ischaemic stroke: Delta/alpha ratio as an optimal QEEG index. Clin Neurophysiol 127:1452–1459. https://doi.org/10.1016/j.clinph.2015.07.014

    Article  PubMed  Google Scholar 

  50. Zahiriev Z (1998) One-year dynamic follow-up of patients with reversible ischaemic neurological deficit using quantitative electroencephalography. Folia Med (Plovdiv) 40(2):26–32

    Google Scholar 

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Correspondence to Stefan Strilciuc.

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The original N-PEP-12 study was approved on 10/12/2015 by the Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy (8 Babeş Street, 400012 Cluj-Napoca, Romania; +40-264-597-256; contact@umfcluj.ro), ref: 507/10.12.2015. Amended twice refs: 82/24.03.2016;104/12.02.2018.

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(DOCX 94 kb)

The following are available online: Table 3. Spearman correlations coefficients (ρ) and p-values between spectral power measured on the alpha band in each of the 7 EEG segments; Table 4. Spearman correlations coefficients (ρ) and p-values between spectral power measured on the beta band in each of the 7 EEG segments; Table 5. Spearman correlations coefficients (ρ) and p-values between spectral power measured on the delta band in each of the 7 EEG segments; Table 6. Spearman correlations coefficients (ρ) and p-values between spectral power measured on the theta band in each of the 7 EEG segments; Table 7. Spearman correlations coefficients (ρ) and p-values between spectral power measured on the DA band in each of the 7 EEG segments; Table 8. Spearman correlations coefficients (ρ) and p-values between spectral power measured on the DTAB band in each of the 7 EEG segments. (DOCX 94 kb)

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Popa, L.L., Iancu, M., Livint, G. et al. N-Pep-12 supplementation after ischemic stroke positively impacts frequency domain QEEG. Neurol Sci 43, 1115–1125 (2022). https://doi.org/10.1007/s10072-021-05406-9

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