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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Perspective

Epilepsy and Alzheimer’s Disease: Current Concepts and Treatment Perspective on Two Closely Related Pathologies

Author(s): Antonio Leo, Martina Tallarico, Miriam Sciaccaluga, Rita Citraro* and Cinzia Costa

Volume 20, Issue 11, 2022

Published on: 08 June, 2022

Page: [2029 - 2033] Pages: 5

DOI: 10.2174/1570159X20666220507020635

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Abstract

The literature on epileptic seizures in Alzheimer's disease has significantly increased over the past decades. Remarkably, several studies suggest a bi-directional link between these two common neurological diseases, with either condition carrying a nearly 2-fold risk of contracting the other in comparison to healthy subjects. In this respect, evidence from both clinical and preclinical studies indicates that epileptogenesis and neurodegeneration possibly share common underlying mechanisms. However, the precise association between epileptogenesis and neurodegeneration still needs to be fully elucidated. Targeted intervention to reduce abnormal network hyperexcitability might constitute a therapeutic strategy to postpone the onset of later neurodegenerative changes and consequent cognitive decline by many years in patients. By virtue of this, an early diagnosis and treatment of seizures in patients with Alzheimer’s disease should be pursued. To date, no guidelines are available for treating epileptic activity in this context, largely due to the paucity of studies sufficient to answer the related questions. Accordingly, clinical trials are mandatory, not only to inform clinicians about symptomatic management of seizures in Alzheimer’s disease patients but also to detect if treatment with antiseizure medications could have disease-modifying effects. Moreover, it will be fundamental to expand the application of animal models of Alzheimer’s disease to comorbid conditions, such as epilepsy both to reveal the mechanisms underlying seizure onset and to better define their role in cognitive decline. Such models could also be useful to identify pharmacological compounds having therapeutically effectiveness as well as reliable early biomarkers for seizures in Alzheimer’s disease.

Keywords: Epilepsy, Alzheimer’s disease, pharmacology, perspective of treatment, network hyperexcitability, neurological comorbidities.

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[1]
James, S.L.; Abate, D.; Abate, K.H.; Abay, S.M.; Abbafati, C.; Abbasi, N.; Abbastabar, H.; Abd-Allah, F.; Abdela, J. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 2018, 392(10159), 1789-1858.
[http://dx.doi.org/10.1016/S0140-6736(18)32279-7] [PMID: 30496104]
[2]
Cummings, J.; Bauzon, J.; Lee, G. Who funds Alzheimer’s disease drug development? Alzheimers Dement. (N. Y.), 2021, 7(1), e12185.
[http://dx.doi.org/10.1002/trc2.12185] [PMID: 34095442]
[3]
Sen, A.; Akinola, M.; Tai, X.Y.; Symmonds, M.; Davis Jones, G.; Mura, S.; Galloway, J.; Hallam, A.; Chan, J.Y.C.; Koychev, I.; Butler, C.; Geddes, J.; Van Der Putt, R.; Thompson, S.; Manohar, S.G.; Frangou, E.; Love, S.; McShane, R.; Husain, M. An investigation of le-vetiracetam in Alzheimer’s disease (ILiAD): A double-blind, placebo-controlled, randomised crossover proof of concept study. Trials, 2021, 22(1), 508.
[http://dx.doi.org/10.1186/s13063-021-05404-4] [PMID: 34332638]
[4]
Lehmann, L.; Lo, A.; Knox, K.M.; Barker-Haliski, M. Alzheimer’s disease and epilepsy: A perspective on the opportunities for overlap-ping therapeutic innovation. Neurochem. Res., 2021, 46(8), 1895-1912.
[http://dx.doi.org/10.1007/s11064-021-03332-y] [PMID: 33929683]
[5]
Powell, G.; Ziso, B.; Larner, A.J. The overlap between epilepsy and Alzheimer’s disease and the consequences for treatment. Expert Rev. Neurother., 2019, 19(7), 653-661.
[http://dx.doi.org/10.1080/14737175.2019.1629289] [PMID: 31238746]
[6]
Vossel, K.A.; Tartaglia, M.C.; Nygaard, H.B.; Zeman, A.Z.; Miller, B.L. Epileptic activity in Alzheimer’s disease: Causes and clinical rele-vance. Lancet Neurol., 2017, 16(4), 311-322.
[http://dx.doi.org/10.1016/S1474-4422(17)30044-3] [PMID: 28327340]
[7]
Taipale, H.; Gomm, W.; Broich, K.; Maier, W.; Tolppanen, A.M.; Tanskanen, A.; Tiihonen, J.; Hartikainen, S.; Haenisch, B. Use of an-tiepileptic drugs and dementia risk-an analysis of finnish health register and german health insurance data. J. Am. Geriatr. Soc., 2018, 66(6), 1123-1129.
[http://dx.doi.org/10.1111/jgs.15358] [PMID: 29566430]
[8]
Helmstaedter, C.; Beghi, E.; Elger, C.E.; Kälviäinen, R.; Malmgren, K.; May, T.W.; Perucca, E.; Trinka, E.; Witt, J.A. No proof of a causal relationship between antiepileptic drug treatment and incidence of dementia. Comment on: Use of antiepileptic drugs and dementia risk-An analysis of Finnish health register and German health insurance data. Epilepsia, 2018, 59(7), 1303-1306.
[http://dx.doi.org/10.1111/epi.14432] [PMID: 29806877]
[9]
Sarkis, R.A.; Meador, K.J. Comment on. J. Am. Geriatr. Soc., 2018, 66(9), 1852-1853.
[http://dx.doi.org/10.1111/jgs.15466] [PMID: 30094829]
[10]
Stefanidou, M.; Beiser, A.S.; Himali, J.J.; Peng, T.J.; Devinsky, O.; Seshadri, S.; Friedman, D. Bi-directional association between epilepsy and dementia: The Framingham Heart Study. Neurology, 2020, 95(24), e3241-e3247.
[http://dx.doi.org/10.1212/WNL.0000000000011077] [PMID: 33097599]
[11]
Helmstaedter, C.; Witt, J.A. Epilepsy and cognition - A bidirectional relationship? Seizure, 2017, 49, 83-89.
[http://dx.doi.org/10.1016/j.seizure.2017.02.017] [PMID: 28284559]
[12]
Beghi, E.; Beghi, M. Epilepsy, antiepileptic drugs and dementia. Curr. Opin. Neurol., 2020, 33(2), 191-197.
[http://dx.doi.org/10.1097/WCO.0000000000000802] [PMID: 32073437]
[13]
Giorgi, F.S.; Saccaro, L.F.; Busceti, C.L.; Biagioni, F.; Fornai, F. Epilepsy and Alzheimer’s disease: Potential mechanisms for an associa-tion. Brain Res. Bull., 2020, 160, 107-120.
[http://dx.doi.org/10.1016/j.brainresbull.2020.04.009] [PMID: 32380189]
[14]
Palop, J.J.; Jones, B.; Kekonius, L.; Chin, J.; Yu, G.Q.; Raber, J.; Masliah, E.; Mucke, L. Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer’s disease-related cognitive deficits. Proc. Natl. Acad. Sci. USA, 2003, 100(16), 9572-9577.
[http://dx.doi.org/10.1073/pnas.1133381100] [PMID: 12881482]
[15]
Pitkänen, A.; Sutula, T.P. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol., 2002, 1(3), 173-181.
[http://dx.doi.org/10.1016/S1474-4422(02)00073-X] [PMID: 12849486]
[16]
Palop, J.J.; Mucke, L. Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: From synapses toward neural networks. Nat. Neurosci., 2010, 13(7), 812-818.
[http://dx.doi.org/10.1038/nn.2583] [PMID: 20581818]
[17]
Amatniek, J.C.; Hauser, W.A.; DelCastillo-Castaneda, C.; Jacobs, D.M.; Marder, K.; Bell, K.; Albert, M.; Brandt, J.; Stern, Y. Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia, 2006, 47(5), 867-872.
[http://dx.doi.org/10.1111/j.1528-1167.2006.00554.x] [PMID: 16686651]
[18]
Palop, J.J.; Mucke, L. Epilepsy and cognitive impairments in Alzheimer disease. Arch. Neurol., 2009, 66(4), 435-440.
[http://dx.doi.org/10.1001/archneurol.2009.15] [PMID: 19204149]
[19]
Costa, C.; Parnetti, L.; D’Amelio, M.; Tozzi, A.; Tantucci, M.; Romigi, A.; Siliquini, S.; Cavallucci, V.; Di Filippo, M.; Mazzocchetti, P.; Liguori, C.; Nobili, A.; Eusebi, P.; Mercuri, N.B.; Calabresi, P. Epilepsy, amyloid-β and D1 dopamine receptors: A possible pathogenetic link? Neurobiol. Aging, 2016, 48, 161-171.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.08.025] [PMID: 27701029]
[20]
Costa, C.; Romoli, M.; Liguori, C.; Farotti, L.; Eusebi, P.; Bedetti, C.; Siliquini, S.; Cesarini, E.N.; Romigi, A.; Mercuri, N.B.; Parnetti, L.; Calabresi, P. Alzheimer’s disease and late-onset epilepsy of unknown origin: Two faces of beta amyloid pathology. Neurobiol. Aging, 2019, 73, 61-67.
[http://dx.doi.org/10.1016/j.neurobiolaging.2018.09.006] [PMID: 30317034]
[21]
Sen, A.; Capelli, V.; Husain, M. Cognition and dementia in older patients with epilepsy. Brain, 2018, 141(6), 1592-1608.
[http://dx.doi.org/10.1093/brain/awy022] [PMID: 29506031]
[22]
Romoli, M.; Sen, A.; Parnetti, L.; Calabresi, P.; Costa, C. Amyloid-β A potential link between epilepsy and cognitive decline. Nat. Rev. Neurol., 2021, 17(8), 469-485.
[http://dx.doi.org/10.1038/s41582-021-00505-9] [PMID: 34117482]
[23]
Sciaccaluga, M.; Megaro, A.; Bellomo, G.; Ruffolo, G.; Romoli, M.; Palma, E.; Costa, C. An unbalanced synaptic transmission: Cause or consequence of the amyloid oligomers neurotoxicity? Int. J. Mol. Sci., 2021, 22(11), 5991.
[http://dx.doi.org/10.3390/ijms22115991] [PMID: 34206089]
[24]
Yang, J.W.; Czech, T.; Felizardo, M.; Baumgartner, C.; Lubec, G. Aberrant expression of cytoskeleton proteins in hippocampus from pa-tients with mesial temporal lobe epilepsy. Amino Acids, 2006, 30(4), 477-493.
[http://dx.doi.org/10.1007/s00726-005-0281-y] [PMID: 16583313]
[25]
Choi, J.; Kim, S.Y.; Kim, H.; Lim, B.C.; Hwang, H.; Chae, J.H.; Kim, K.J.; Oh, S.; Kim, E.Y.; Shin, J.S. Serum α-synuclein and IL-1β are increased and correlated with measures of disease severity in children with epilepsy: Potential prognostic biomarkers? BMC Neurol., 2020, 20(1), 85.
[http://dx.doi.org/10.1186/s12883-020-01662-y] [PMID: 32151248]
[26]
Li, A.; Choi, Y.S.; Dziema, H.; Cao, R.; Cho, H.Y.; Jung, Y.J.; Obrietan, K. Proteomic profiling of the epileptic dentate gyrus. Brain Pathol., 2010, 20(6), 1077-1089.
[http://dx.doi.org/10.1111/j.1750-3639.2010.00414.x] [PMID: 20608933]
[27]
Hussein, A.M.; Eldosoky, M.; El-Shafey, M.; El-Mesery, M.; Ali, A.N.; Abbas, K.M.; Abulseoud, O.A. Effects of metformin on apoptosis and α-synuclein in a rat model of pentylenetetrazole-induced epilepsy. Can. J. Physiol. Pharmacol., 2019, 97(1), 37-46.
[http://dx.doi.org/10.1139/cjpp-2018-0266] [PMID: 30308130]
[28]
Morris, M.; Sanchez, P.E.; Verret, L.; Beagle, A.J.; Guo, W.; Dubal, D.; Ranasinghe, K.G.; Koyama, A.; Ho, K.; Yu, G.Q.; Vossel, K.A.; Mucke, L. Network dysfunction in α-synuclein transgenic mice and human Lewy body dementia. Ann. Clin. Transl. Neurol., 2015, 2(11), 1012-1028.
[http://dx.doi.org/10.1002/acn3.257] [PMID: 26732627]
[29]
Peters, S.T.; Fahrenkopf, A.; Choquette, J.M.; Vermilyea, S.C.; Lee, M.K.; Vossel, K. Ablating tau reduces hyperexcitability and moderates electroencephalographic slowing in transgenic mice expressing A53T human α-synuclein. Front. Neurol., 2020, 11, 563.
[http://dx.doi.org/10.3389/fneur.2020.00563] [PMID: 32636798]
[30]
Tweedy, C.; Kindred, N.; Curry, J.; Williams, C.; Taylor, J.P.; Atkinson, P.; Randall, F.; Erskine, D.; Morris, C.M.; Reeve, A.K.; Clowry, G.J.; LeBeau, F.E.N. Hippocampal network hyperexcitability in young transgenic mice expressing human mutant alpha-synuclein. Neurobiol. Dis., 2021, 149, 105226.
[http://dx.doi.org/10.1016/j.nbd.2020.105226] [PMID: 33347975]
[31]
Asadollahi, M.; Atazadeh, M.; Noroozian, M. Seizure in Alzheimer’s disease: An underestimated phenomenon. Am. J. Alzheimers Dis. Other Demen., 2019, 34(2), 81-88.
[http://dx.doi.org/10.1177/1533317518813551] [PMID: 30595042]
[32]
Lozano, R.; Fullman, N.; Mumford, J.E.; Knight, M.; Barthelemy, C.M.; Abbafati, C.; Abbastabar, H.; Abd-Allah, F. Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990-2019: A systematic anal-ysis for the Global Burden of Disease Study 2019. Lancet, 2020, 396(10258), 1250-1284.
[http://dx.doi.org/10.1016/S0140-6736(20)30750-9] [PMID: 32861314]
[33]
Giorgi, F.S.; Guida, M.; Vergallo, A.; Bonuccelli, U.; Zaccara, G. Treatment of epilepsy in patients with Alzheimer’s disease. Expert Rev. Neurother., 2017, 17(3), 309-318.
[http://dx.doi.org/10.1080/14737175.2017.1243469] [PMID: 27687685]
[34]
Kanner, A.M.; Helmstaedter, C.; Sadat-Hossieny, Z.; Meador, K. Cognitive disorders in epilepsy I: Clinical experience, real-world evi-dence and recommendations. Seizure, 2020, 83, 216-222.
[http://dx.doi.org/10.1016/j.seizure.2020.10.009] [PMID: 33127274]
[35]
Perucca, P.; Gilliam, F.G. Adverse effects of antiepileptic drugs. Lancet Neurol., 2012, 11(9), 792-802.
[http://dx.doi.org/10.1016/S1474-4422(12)70153-9] [PMID: 22832500]
[36]
Helmstaedter, C.; Sadat-Hossieny, Z.; Kanner, A.M.; Meador, K.J. Cognitive disorders in epilepsy II: Clinical targets, indications and se-lection of test instruments. Seizure, 2020, 83, 223-231.
[http://dx.doi.org/10.1016/j.seizure.2020.09.031] [PMID: 33172763]
[37]
Meador, K.J.; Gevins, A.; Leese, P.T.; Otoul, C.; Loring, D.W. Neurocognitive effects of brivaracetam, levetiracetam, and lorazepam. Epilepsia, 2011, 52(2), 264-272.
[http://dx.doi.org/10.1111/j.1528-1167.2010.02746.x] [PMID: 20887370]
[38]
Rowan, A.J.; Ramsay, R.E.; Collins, J.F.; Pryor, F.; Boardman, K.D.; Uthman, B.M.; Spitz, M.; Frederick, T.; Towne, A.; Carter, G.S.; Marks, W.; Felicetta, J.; Tomyanovich, M.L. New onset geriatric epilepsy: A randomized study of gabapentin, lamotrigine, and carbamaze-pine. Neurology, 2005, 64(11), 1868-1873.
[http://dx.doi.org/10.1212/01.WNL.0000167384.68207.3E] [PMID: 15955935]
[39]
Saetre, E.; Perucca, E.; Isojärvi, J.; Gjerstad, L.; Babic, T.; Hodoba, D.; Vrca, A.; Lusic, I.; Kälviäinen, R.; Keränen, T.; Koivisto, K.; Ko-tila, M.; De Toffol, B.; Geraud, G.; Jouanny, P.; Lemesle, M.; Marchal, C.; Neau, J.P.; Thomas, P.; Tillier, J.N.; Touchon, J.; Vespignani, H.; Avanzini, G.; Canevini, M.P.; Defanti, C.A.; Antonini, L.; Beghi, E.; Benetello, P.; Mancia, D.; Mazza, S.; Mutani, R.; Monaco, F.; Pisa-ni, F.; Regesta, G.; Specchio, L.M.; Striano, S.; Tartara, A.; Galimberti, C.A.; Tassinari, C.A.; Tinuper, P.; Toso, V.; Zaccara, G.; Aasly, J.; Johnsen, H.J.; Sando, S.B.; Albretsen, C.; Engelsen, B.; Lilleboe, A.; Hagen, T.; Hauge, T.B.; Henriksen, O.A.; Kaass, B.; Kloster, R.; Skogen, P.; Kristensen, T.; Lossius, M.; Monstad, I.; Svendsen, T.; Tauboll, E.; Tjensvoll, A.B. An international multicenter randomized double-blind controlled trial of lamotrigine and sustained-release carbamazepine in the treatment of newly diagnosed epilepsy in the elder-ly. Epilepsia, 2007, 48(7), 1292-1302.
[http://dx.doi.org/10.1111/j.1528-1167.2007.01128.x] [PMID: 17561956]
[40]
Brodie, M.J.; Overstall, P.W.; Giorgi, L. Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Res., 1999, 37(1), 81-87.
[http://dx.doi.org/10.1016/S0920-1211(99)00039-X] [PMID: 10515178]
[41]
Arif, H.; Buchsbaum, R.; Pierro, J.; Whalen, M.; Sims, J.; Resor, S.R., Jr; Bazil, C.W.; Hirsch, L.J. Comparative effectiveness of 10 antiepi-leptic drugs in older adults with epilepsy. Arch. Neurol., 2010, 67(4), 408-415.
[http://dx.doi.org/10.1001/archneurol.2010.49] [PMID: 20385905]
[42]
Rao, S.C.; Dove, G.; Cascino, G.D.; Petersen, R.C. Recurrent seizures in patients with dementia: Frequency, seizure types, and treatment outcome. Epilepsy Behav., 2009, 14(1), 118-120.
[http://dx.doi.org/10.1016/j.yebeh.2008.08.012] [PMID: 18782632]
[43]
Profenno, L.A.; Jakimovich, L.; Holt, C.J.; Porsteinsson, A.; Tariot, P.N. A randomized, double-blind, placebo-controlled pilot trial of safety and tolerability of two doses of divalproex sodium in outpatients with probable Alzheimer’s disease. Curr. Alzheimer Res., 2005, 2(5), 553-558.
[http://dx.doi.org/10.2174/156720505774932205] [PMID: 16375658]
[44]
Tariot, P.N.; Schneider, L.S.; Cummings, J.; Thomas, R.G.; Raman, R.; Jakimovich, L.J.; Loy, R.; Bartocci, B.; Fleisher, A.; Ismail, M.S.; Porsteinsson, A.; Weiner, M.; Jack, C.R., Jr; Thal, L.; Aisen, P.S. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch. Gen. Psychiatry, 2011, 68(8), 853-861.
[http://dx.doi.org/10.1001/archgenpsychiatry.2011.72] [PMID: 21810649]
[45]
Liu, J.; Wang, L.N. Treatment of epilepsy for people with Alzheimer’s disease. Cochrane Database Syst. Rev., 2021, 5, CD011922.
[http://dx.doi.org/10.1002/14651858.CD011922.pub4] [PMID: 33973646]
[46]
Born, H.A. Seizures in Alzheimer’s disease. Neuroscience, 2015, 286, 251-263.
[http://dx.doi.org/10.1016/j.neuroscience.2014.11.051] [PMID: 25484360]

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