Incidence of dementia in patients with adult-onset epilepsy of unknown causes

Abstract

Epilepsy is generally considered to occur most commonly in childhood; however, several epidemiological studies confirmed that its occurrence increases from middle age [ [1] Hauser W.A. Seizure disorders: the changes with age. Epilepsia. 1992; 33: S6-S14 Crossref PubMed Scopus (344) Google Scholar , [2] Olafsson E. Ludvigsson P. Gudmundsson G. Hesdorffer D. Kjartansson O. Hauser W.A. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study. Lancet Neurol. 2005; 4: 627-634 Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar ], and is the third most common neurological disease affecting the elderly, following dementia and cerebrovascular disease (CVD) [ [3] Brodie M.J. Kwan P. Epilepsy in elderly people. BMJ. 2005; 331: 1317-1322 Crossref PubMed Scopus (141) Google Scholar , [4] Werhahn K.J. Epilepsy in the elderly. Dtsch Arztebl Int. 2009; 106: 135-142 PubMed Google Scholar ]. These diseases interact with each other in later life. The leading etiology of elderly-onset epilepsy is CVD [ [5] Hauser W.A. Rowan A.J. Ramsay R.E. Epidemiology of Seizures and Epilepsy in the Elderly. Butterworth-Heinemann, Boston1997: 7-18 Google Scholar , [6] Wallace H. Shorvon S. Tallis R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922, and age-specific fertility rates of women with epilepsy. Lancet. 1998; 352: 1970-1973 Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar ], and CVD is a major risk factor for dementia with neurodegenerative disease, especially Alzheimer's disease (AD) [ [7] Petrovitch H. Ross G.W. Steinhorn S.C. Abott R.D. Markesbery W. Davis D. et al. AD lesions and infarcts in demented and non-demented Japanese-American men. Ann. Neurol. 2005; 57: 98-103 Crossref PubMed Scopus (202) Google Scholar , [8] J. Obrien R. Vascular dementia: atherosclerosis, cognition and Alzheimer's disease. Curr. Alzheimer Res. 2011; 8: 341-344 Crossref PubMed Scopus (13) Google Scholar ]. Adult-onset epilepsy is considered as a consequence of structural damage of the central nervous system (CNS), and the existence of AD, a typical neurodegenerative disease, also increases the occurrence of epilepsy [ [9] Scarmeas N. Honig L.S. Choi H. Cantero J. Brandt J. Blacker D. et al. Seizures in Alzheimer disease: who, when, and how common?. Arch. Neurol. 2009; 66: 992-997 Crossref PubMed Scopus (221) Google Scholar ]. This clinical finding is supported by several basic studies using a transgenic mouse model of AD, which demonstrated that deposited amyloid-β (Aβ) causes epileptiform discharges in the cortex, nonconvulsive seizures, and cognitive dysfunction [ [10] Palop J.J. Chin J. Roberson E.D. Wang J. Thwin M.T. Bien-Ly N. et al. Compensatory remodering of inhibitory hippocampal circuits in mouse models in Alzheimer's disease. Neuron. 2007; 55: 697-711 Abstract Full Text Full Text PDF PubMed Scopus (1121) Google Scholar , [11] Huang Y. Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012; 148: 1204-1222 Abstract Full Text Full Text PDF PubMed Scopus (1358) Google Scholar ]. Taking into account the evidence that Aβ deposition starts >10 years before clinical signs of AD appear [ [12] Villemagne V.L. Burnham S. Bourgeat P. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013; 12: 357-367 Abstract Full Text Full Text PDF PubMed Scopus (1410) Google Scholar ], epilepsy may develop earlier than AD. To test this hypothesis, we retrospectively studied the occurrence of AD in patients with adult-onset epilepsy of unknown causes to elucidate whether these patients are more likely to develop AD than control patients. Moreover, to determine whether an atherosclerotic factor affects the occurrence of AD, we also investigated the occurrence of CVD in both groups.