Epilepsy in patients with Alzheimer's disease: A systematic review

Miranda, Diane da Costa; Brucki, Sonia Maria Dozzi

doi:10.1590/S1980-57642014DN81000010

ABSTRACT

Alzheimer's disease (AD) and epilepsy are common disorders in the elderly. Evidence demonstrates that patients with AD have an increased risk of developing epilepsy and seizures. Objective: To review epidemiological, clinical and treatment aspects of epilepsy and AD. Methods: We reviewed databases (PubMED, LiLACS, Scielo) conducting a search for manuscripts using the terms Alzheimer's disease and epilepsy. Results: Manuscripts related to the areas of interest were reviewed. Studies revealed that epilepsy is more frequent among AD patients. The combined presence of the two disorders may be related to mechanisms of neuronal hyperexcitability as a consequence of amyloid-beta protein (Ab) or phosphorylated tau accumulation, as well as to structural changes in cortical and hippocampal regions. Available data suggest that the new generation of antiepileptic drugs (AEDs) are better tolerated in the elderly population, and may also be the best option in patients with AD and epilepsy. Conclusion: Further prospective studies involving evaluation of concomitant dementia and epilepsy, neurophysiological findings and biomarkers need to be performed.

Key words:
Alzheimer's disease; epilepsy; dementia; antiepileptic drugs

RESUMO

Doença de Alzheimer (DA) e Epilepsia são desordens frequentemente vistas em idosos. Evidências mostram que pacientes com DA possuem um risco aumentado de desenvolver crises e epilepsia. Objetivo: Rever aspectos epidemiológicos, clínicos e de tratamento relacionados à DA e epilepsia. Métodos: Nós revimos as bases de dados (PubMED, LiLACS, Scielo) procurando por manuscritos com termos: Doença de Alzheimer e epilepsia. Resultados: Manuscritos que continham assuntos de nossa area de interesse foram revisados. Os estudos mostram que a frequência de epilepsia é maior em pacientes com DA, possivelmente ligados à deposição de beta-amiloide e proteína tau, que aumentam a hiperexcitabilidade neuronal, bem como alterações estruturais na região hipocampal. Dados disponíveis sugerem que as drogas antiepilépticas de nova geração são mais bem toleradas na população idosa, e talvez também sejam a melhor escolha nos pacientes com DA e epilepsia. Conclusão: Mais estudos prospectivos com evolução de demência e epilepsia concomitantes com achados neurofisiológicos e de biomarcadores necessitam ser desenvolvidos.

Palavras-chave:
doença de Alzheimer; epilepsia; demência; drogas antiepilépticas

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REFERENCES

¹
Jenssen S, Schere D. Treatment and Management of Epilepsy in the Elderly Demented Patient. Am J Alzheimers Dis Other Demen 2010;25:18-26.
²
Hommet C, Mondon K, Camus V, De Toffol B, Constans T. Epilepsy and Dementia in the Elderly. Dement Geriatr Cogn Disord 2008;25:293-300.
³
Friedman D, Honig LS, Scarmeas N. Seizures and Epilepsy in Alzheimer's Disease. CNS Neurosci Ther 2012;18:285-294.
⁴
Pandis D, Scarmeas M. Seizures in Alzheimer Disease:Clinical and Epidemiological Data. Epilepsy Curr 2012;12:184-187.
⁵
Almeida MA, Fonseca SR, Santos APB. Epilepsia e Demência em uma Amostra de Pacientes Idosos Acompanhados em Serviço Terciário. J Epilepsy Clin Neurophysiol 2009;15:61-64.
⁶
Ziyatdinova S, Gurevicius K, Kutchiashvili N, et al. Spontaneous epileptiform discharges in a mouse model of Alzheimer's disease are suppressed by antiepileptic drugs that block sodium channels. Epilepsy Res 2011;94:75-85.
⁷
Hommet C, Hureaux R, Barré J, Constans T, Berrut G.Epileptic seizures in clinically diagnosed Alzheimer's disease:report from a geriatric medicine population. Aging Clin Exp Res 2007;19:430-431.
⁸
Imfeld P, Bodmer M, Schuerch M, Jick SS, Meier CR. Seizures in patients with Alzheimer's disease or vascular dementia:A population-based nested case-control analysis. Epilepsia 2013;54:700-707.
⁹
Irizarry MC, Jin S, He F, et al. Incidence of New-Onset Seizures in Mild to Moderate Alzheimer Disease. Arch Neurol 2012;69:368-372.
¹⁰
Amatniek JC, Hauser WA, DelCastillo-Castaneda C. Incidence and Predictors of Seizures in Patients with Alzheimer's Disease. Epilepsia 2006; 47:867-872.
¹¹
Scarmeas N, Honi LS, Choi H. Seizures in Alzheimer Disease: Who, When, and How Common? Arch Neurol 2009;66:992-997.
¹²
Larner AJ. Epileptic Seizures in AD Patients. Neuromol Med 2010;12: 71-77.
¹³
Larner AJ. Presenilin-1 mutation Alzheimer's disease:A genetic epilepsy syndrome? Epilepsy Behav 2011;21:20-22.
¹⁴
Noebels J. A perfect storm:Converging paths of epilepsy and Alzheimer's dementia intersect in the hippocampal formation. Epilepsia 2011; 52:39-46.
¹⁵
Bernardi S, Scaldaferri N, Vanacore N, et al. Seizures in Alzheimer's disease:a retrospective study of a cohort of outpatients. Epileptic Disord 2010;12:16-21.
¹⁶
Rao SC, Dove G, Cascino GD, Petersen RC. Recurrent seizures in patients with dementia:Frequency, seizure types, and treatment outcome. Epilepsy Behav 2009;14:118-120.
¹⁷
Gurevicius K, Lipponen A, Tanila H. Increased cortical and thalamic excitability in freely moving APPswe/PS1dE9 mice modeling epileptic activity associated with Alzheimer's disease. Cereb Cortex 2013;23:1148-1158.
¹⁸
Palop JJ, Mucke L. Epilepsy and Cognitive Impairments in Alzheimer Disease. Arch Neurol 2009;66:435-445.
¹⁹
Liu Q, Xie X, Lukas RJ, John PAS, Wu J. A Novel Nicotinic Mechanism Underlies b-Amyloid-Induced Neuronal Hyperexcitation. J Neurosci 2013; 33:7253-7263.
²⁰
Larner AJ, Marson AG. Epileptic Seizures in Alzheimer's Disease:Another Fine MESS? J Alzheimers Dis 2011;25:417-419.
²¹
Pilotto A, Padovani A, Borroni B. Clinical, Biological, and Imaging Features of Monogenic Alzheimer's Disease. BioMed Res Int 2013; 2013:1-9.
²²
Palop JJ, Chin J, Roberson ED, et al. Aberrant Excitatory Neuronal Activity and Compensatory Remodelingof Inhibitory Hippocampal Circuits in Mouse Models of Alzheimer's Disease. Neuron 2007;55:697-711.
²³
Minkeviciene R, Rheims S, Dobszay MB, et al. Amyloid b-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy. J Neurosci 2009; 29:3453-3462.
²⁴
DeVos SL, Goncharoff DK, Chen G, et al. Antisense Reduction of Tau in Adult Mice Protects against Seizures. J Neurosci 2013;33:12887-12897.
²⁵
Zheng P, Shultz SR, Hovens CM, Velakoulis D, Jones NC, O'Brien TJ. Hyperphosphorylated Tau is Implicated in Acquired Epilepsy and Neuropsychiatric Comorbidities. Mol Neurobiol 2013;10:1007-1014.
²⁶
Holth JK, Bomben VC, Reed JG. Tau Loss Attenuates Neuronal Network Hyperexcitability in Mouse and Drosophila Genetic Models of Epilepsy. J Neurosci 2013;33:1651-1659.
²⁷
Heinzen EL, Yoon W, Weale ME, et al. Alternative ion channel splicing in mesial temporal lobe epilepsy and Alzheimer's disease. Genome Biol 2007;8:1-18.
²⁸
Belcastro V, Costa C, Galletti F, Pisani F, Calabresi P, Parnetti L. Levetiracetam monotherapy in Alzheimer patients with late-onset seizures:a prospective observational study. Eur J Neurol 2007;14:1176-1178.
²⁹
Cumbo E, Ligori LD. Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer's disease. Epilepsy Behav 2010;17:461-466.
³⁰
Lippa CF, Rosso A, Hepler M, Jenssen S, Pillai J, Irwin D. Levetiracetam:a practical option for seizure management in elderly patients with cognitive impairment. Am J Alzheimer Dis Other Demen 2010;25:149-154.

Publication Dates

Publication in this collection
Jan-Mar 2014

History

Received
02 Nov 2013
Accepted
13 Jan 2014

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹
Jenssen S, Schere D. Treatment and Management of Epilepsy in the Elderly Demented Patient. Am J Alzheimers Dis Other Demen 2010;25:18-26.

[2] ²
Hommet C, Mondon K, Camus V, De Toffol B, Constans T. Epilepsy and Dementia in the Elderly. Dement Geriatr Cogn Disord 2008;25:293-300.

[3] ³
Friedman D, Honig LS, Scarmeas N. Seizures and Epilepsy in Alzheimer's Disease. CNS Neurosci Ther 2012;18:285-294.

[4] ⁴
Pandis D, Scarmeas M. Seizures in Alzheimer Disease:Clinical and Epidemiological Data. Epilepsy Curr 2012;12:184-187.

[5] ⁵
Almeida MA, Fonseca SR, Santos APB. Epilepsia e Demência em uma Amostra de Pacientes Idosos Acompanhados em Serviço Terciário. J Epilepsy Clin Neurophysiol 2009;15:61-64.

[6] ⁶
Ziyatdinova S, Gurevicius K, Kutchiashvili N, et al. Spontaneous epileptiform discharges in a mouse model of Alzheimer's disease are suppressed by antiepileptic drugs that block sodium channels. Epilepsy Res 2011;94:75-85.

[7] ⁷
Hommet C, Hureaux R, Barré J, Constans T, Berrut G.Epileptic seizures in clinically diagnosed Alzheimer's disease:report from a geriatric medicine population. Aging Clin Exp Res 2007;19:430-431.

[8] ⁸
Imfeld P, Bodmer M, Schuerch M, Jick SS, Meier CR. Seizures in patients with Alzheimer's disease or vascular dementia:A population-based nested case-control analysis. Epilepsia 2013;54:700-707.

[9] ⁹
Irizarry MC, Jin S, He F, et al. Incidence of New-Onset Seizures in Mild to Moderate Alzheimer Disease. Arch Neurol 2012;69:368-372.

[10] ¹⁰
Amatniek JC, Hauser WA, DelCastillo-Castaneda C. Incidence and Predictors of Seizures in Patients with Alzheimer's Disease. Epilepsia 2006; 47:867-872.

[11] ¹¹
Scarmeas N, Honi LS, Choi H. Seizures in Alzheimer Disease: Who, When, and How Common? Arch Neurol 2009;66:992-997.

[12] ¹²
Larner AJ. Epileptic Seizures in AD Patients. Neuromol Med 2010;12: 71-77.

[13] ¹³
Larner AJ. Presenilin-1 mutation Alzheimer's disease:A genetic epilepsy syndrome? Epilepsy Behav 2011;21:20-22.

[14] ¹⁴
Noebels J. A perfect storm:Converging paths of epilepsy and Alzheimer's dementia intersect in the hippocampal formation. Epilepsia 2011; 52:39-46.

[15] ¹⁵
Bernardi S, Scaldaferri N, Vanacore N, et al. Seizures in Alzheimer's disease:a retrospective study of a cohort of outpatients. Epileptic Disord 2010;12:16-21.

[16] ¹⁶
Rao SC, Dove G, Cascino GD, Petersen RC. Recurrent seizures in patients with dementia:Frequency, seizure types, and treatment outcome. Epilepsy Behav 2009;14:118-120.

[17] ¹⁷
Gurevicius K, Lipponen A, Tanila H. Increased cortical and thalamic excitability in freely moving APPswe/PS1dE9 mice modeling epileptic activity associated with Alzheimer's disease. Cereb Cortex 2013;23:1148-1158.

[18] ¹⁸
Palop JJ, Mucke L. Epilepsy and Cognitive Impairments in Alzheimer Disease. Arch Neurol 2009;66:435-445.

[19] ¹⁹
Liu Q, Xie X, Lukas RJ, John PAS, Wu J. A Novel Nicotinic Mechanism Underlies b-Amyloid-Induced Neuronal Hyperexcitation. J Neurosci 2013; 33:7253-7263.

[20] ²⁰
Larner AJ, Marson AG. Epileptic Seizures in Alzheimer's Disease:Another Fine MESS? J Alzheimers Dis 2011;25:417-419.

[21] ²¹
Pilotto A, Padovani A, Borroni B. Clinical, Biological, and Imaging Features of Monogenic Alzheimer's Disease. BioMed Res Int 2013; 2013:1-9.

[22] ²²
Palop JJ, Chin J, Roberson ED, et al. Aberrant Excitatory Neuronal Activity and Compensatory Remodelingof Inhibitory Hippocampal Circuits in Mouse Models of Alzheimer's Disease. Neuron 2007;55:697-711.

[23] ²³
Minkeviciene R, Rheims S, Dobszay MB, et al. Amyloid b-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy. J Neurosci 2009; 29:3453-3462.

[24] ²⁴
DeVos SL, Goncharoff DK, Chen G, et al. Antisense Reduction of Tau in Adult Mice Protects against Seizures. J Neurosci 2013;33:12887-12897.

[25] ²⁵
Zheng P, Shultz SR, Hovens CM, Velakoulis D, Jones NC, O'Brien TJ. Hyperphosphorylated Tau is Implicated in Acquired Epilepsy and Neuropsychiatric Comorbidities. Mol Neurobiol 2013;10:1007-1014.

[26] ²⁶
Holth JK, Bomben VC, Reed JG. Tau Loss Attenuates Neuronal Network Hyperexcitability in Mouse and Drosophila Genetic Models of Epilepsy. J Neurosci 2013;33:1651-1659.

[27] ²⁷
Heinzen EL, Yoon W, Weale ME, et al. Alternative ion channel splicing in mesial temporal lobe epilepsy and Alzheimer's disease. Genome Biol 2007;8:1-18.

[28] ²⁸
Belcastro V, Costa C, Galletti F, Pisani F, Calabresi P, Parnetti L. Levetiracetam monotherapy in Alzheimer patients with late-onset seizures:a prospective observational study. Eur J Neurol 2007;14:1176-1178.

[29] ²⁹
Cumbo E, Ligori LD. Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer's disease. Epilepsy Behav 2010;17:461-466.

[30] ³⁰
Lippa CF, Rosso A, Hepler M, Jenssen S, Pillai J, Irwin D. Levetiracetam:a practical option for seizure management in elderly patients with cognitive impairment. Am J Alzheimer Dis Other Demen 2010;25:149-154.

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