Drugs & Aging

, Volume 20, Issue 11, pp 791–803

Seizures in Elderly Patients with Dementia

Epidemiology and Management
  • Mario F. Mendez
  • Gerald T. H. Lim
Therapy In Practice


Epileptic seizures occur in patients with dementia at a higher prevalence than among healthy elderly individuals. The incidence of seizures among patients with dementia varies with the aetiology of the dementing illness. In patients with Alzheimer’s disease (the most common form of dementia), approximately 10–22% have at least one unprovoked seizure. Seizures usually occur in later stages of Alzheimer’s disease, on average, ≥6 years into the course of the disease. Seizures in Alzheimer’s disease are more likely to occur with early-onset disease, particularly if there is a familial presenilin I mutation. The incidence of seizures in other dementing diseases is less clear.

There are special considerations regarding the management of seizures in the elderly with dementia. First, the presence of cognitive impairment may impede an accurate diagnosis of seizures. Clinicians may also mistake seizure manifestations for symptoms of the underlying dementia. Second, since most dementia patients are elderly, there are pharmacokinetic changes with aging that affect the use of antiepileptic drugs. Third, antiepileptic drugs have potential cognitive adverse effects that may worsen dementia.

Although few studies are available, extrapolations from research in young people and elderly patients without dementia provide several recommendations for the management of seizures in patients with dementia: exclude symptomatic causes of seizures before committing to antiepileptic drug therapy; treat after a first seizure if there is evidence of focal neurological involvement or a risk of recurrent seizures; use antiepileptic drugs with minimal cognitive adverse effects, such as carbamazepine, valproic acid, gabapentin and lamotrigine; and use the lowest possible dosage and monitor antiepileptic drug levels, where possible.


  1. 1.
    Evans DA, Scherr PA, Smith LA, et al. The east Boston Alzheimer’s disease registry. Aging (Milano) 1990; 2: 298–302Google Scholar
  2. 2.
    Henderson AS. Epidemiology of dementia disorders. Adv Neurol 1990; 51: 15–25PubMedGoogle Scholar
  3. 3.
    Katzman R. Education and the prevalence of dementia and Alzheimer’s disease. Neurology 1993; 43: 13–20PubMedCrossRefGoogle Scholar
  4. 4.
    Canadian Study of Health and Aging Working Group. Canadian Study of Health and Aging: study methods and prevalence of dementia. CMAJ 1994; 150: 899–912Google Scholar
  5. 5.
    Breteler MM, Claus JJ, van Duijn CM, et al. Epidemiology of Alzheimer’s disease. Epidemiol Rev 1992; 14: 59–82PubMedGoogle Scholar
  6. 6.
    General Accounting Office Report B-277607. Health, Education, and Human Services division. Alzheimer’s Disease Prevalence. Washington (DC): United States General Accounting Office, 1998 Jan 28Google Scholar
  7. 7.
    Andersen K, Nielsen H, Lolk A, et al. Incidence of very mild to severe dementia and Alzheimer’s disease in Denmark: the Odense Study. Neurology 1999; 52: 85–90PubMedCrossRefGoogle Scholar
  8. 8.
    Fillenbaum GG, Heyman A, Huber MS, et al. The prevalence and 3-year incidence of dementia in older Black and White community residents. J Clin Epidemiol 1998; 51: 587–95PubMedCrossRefGoogle Scholar
  9. 9.
    Schoenberg BS, Anderson DW, Haerer AF. Severe dementia: prevalence and clinical features in a biracial US population. Arch Neurol 1985; 42: 740–3PubMedCrossRefGoogle Scholar
  10. 10.
    Department of Commerce. Aging/elderly population data. United States Census Bureau [online]. Available from URL: http://www.census.gov/population/www/socdemo/age.html#elderly [Accessed 2003 Jul 31]
  11. 11.
    Drachman DA. If we live long enough, will we all be demented? Neurology 1994; 44: 1563–5PubMedCrossRefGoogle Scholar
  12. 12.
    Jorm AF, Korten AE, Henderson AS. The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatr Scand 1987; 76: 465–79PubMedCrossRefGoogle Scholar
  13. 13.
    Jorm AF. Cross-national comparisons of the occurrence of Alzheimer’s and vascular dementias. Eur Arch Psychiatry Clin Neurosci 1991; 240: 218–22PubMedCrossRefGoogle Scholar
  14. 14.
    Paykel ES, Brayne C, Huppert FA, et al. Incidence of dementia in a population older than 75 years in the United Kingdom. Arch Gen Psychiatry 1994; 51: 325–32PubMedCrossRefGoogle Scholar
  15. 15.
    Kokman E, Beard M, Offord KP, et al. Prevalence of medically diagnosed dementia in a defined United States population: Rochester, Minnesota, 1975 Jan 1. Neurology 1989; 39: 773–6CrossRefGoogle Scholar
  16. 16.
    Mendez MF, Cummings JL. Dementia: a clinical approach. 3rd ed. Philadelphia (PA): Butterworth-Heinemann, 2003Google Scholar
  17. 17.
    Drach LM, Steinmetz HE, Wach S, et al. High proportion of dementia with Lewy bodies in the postmortems of a mental hospital in Germany. Int J Geriatr Psychiatry 1997; 12: 301–6PubMedCrossRefGoogle Scholar
  18. 18.
    Stevens T, Livingston G, Kitchen G, et al. Islington study of dementia subtypes in the community. Br J Psychiatry 2002; 180: 270–6PubMedCrossRefGoogle Scholar
  19. 19.
    Mendez MF, Mastri AR, Sung JH, et al. Neuropathologically confirmed Alzheimer’s disease: clinical diagnoses in 394 cases. J Geriatr Psychiatry Neurol 1991; 4: 26–9PubMedCrossRefGoogle Scholar
  20. 20.
    Roman GC, Goldstein M. A population-based study of dementia in 85-year-olds. N Engl J Med 1993; 329: 63–4PubMedGoogle Scholar
  21. 21.
    Sander JWAS, Hart YM, Johnson AL, et al. National general practice study of epilepsy: newly diagnosed people with epilepsy in a general population. Lancet 1990; 20: 442–8Google Scholar
  22. 22.
    Tallis R, Hall G, Craig I, et al. How common are epileptic seizures in old age? Age Ageing 1991; 20: 442–8PubMedCrossRefGoogle Scholar
  23. 23.
    Hauser WA. Seizure disorders: the changes with age. Epilepsia 1992; 33Suppl. 4: S6–S14PubMedCrossRefGoogle Scholar
  24. 24.
    De la Court A, Breteler MM, Meinardi H, et al. Prevalence of epilepsy in the elderly: the Rotterdam Study. Epilepsia 1996; 37: 141–7PubMedCrossRefGoogle Scholar
  25. 25.
    Thomas RJ. Seizures and epilepsy in the elderly. Arch Intern Med 1997; 157: 605–17PubMedCrossRefGoogle Scholar
  26. 26.
    Faught E. Epidemiology and drug treatment of epilepsy in elderly people. Drugs Aging 1999; 15: 255–69PubMedCrossRefGoogle Scholar
  27. 27.
    Cloyd JC, Lackner TE, Leppik IE. Antiepileptics in the elderly: pharmacoepidemiology and pharmacokinetics. Arch Fam Med 1994; 3: 589–98PubMedCrossRefGoogle Scholar
  28. 28.
    Garrard J, Cloyd J, Gross C, et al. Factors associated with antiepileptic drug use among elderly nursing home residents. J Gerontol A Biol Sci Med Sci 2000; 55: M384–92PubMedCrossRefGoogle Scholar
  29. 29.
    Lackner T, Cloyd JC, Thomas LW, et al. Antiepileptic drug use in nursing home residents: effect of age, gender, and comedication on patterns of use. Epilepsia 1998; 39: 1083–7PubMedCrossRefGoogle Scholar
  30. 30.
    Hauser WA, Morris ML, Heston LL, et al. Seizures and myoclonus in patients with Alzheimer’s disease. Neurology 1986; 36: 1226–30PubMedCrossRefGoogle Scholar
  31. 31.
    Hesdorffer DC, Hauser WA, Annegers JF, et al. Dementia and adult onset unprovoked seizures. Neurology 1996; 46: 727–30PubMedCrossRefGoogle Scholar
  32. 32.
    McAreavey MJ, Ballinger BR, Fenton GW. Epileptic seizures in elderly patients with Dementia. Epilepsia 1992; 33: 657–60PubMedCrossRefGoogle Scholar
  33. 33.
    Romanelli M, Morris JC, Ashkin K, et al. Advanced Alzheimer’s disease is a risk factor for late onset seizures. Arch Neurol 1990; 47: 847–50PubMedCrossRefGoogle Scholar
  34. 34.
    Mendez MF, Catanzarro P, Doss RC, et al. Seizures in Alzheimer’s disease: clinicopathologic study. J Geriatr Psychiatry Neurol 1994; 7: 230–3PubMedGoogle Scholar
  35. 35.
    Sjogren T, Sjogren H, Lindgren AGH. Morbus Alzheimer and morbus pick: a genetic, clinical and pathoanatomical study. Acta Psychiatr Neurol Scand 1952; 82 Suppl.: 75–93Google Scholar
  36. 36.
    Volicer L, Smith S, Volicer BJ. Effect of seizures on progression of dementia of the Alzheimer type. Dementia 1995; 6: 258–63PubMedGoogle Scholar
  37. 37.
    Despland PA. Demences et crises epileptiques tardives. Schweiz Rundsch Med Prax 1997; 86: 1414–7Google Scholar
  38. 38.
    Heyman A, Wilkinson WE, Hurwitz BJ, et al. Early onset Alzheimer’s disease: clinical predictors of institutionalization and death. Neurology 1987; 37: 980–4PubMedCrossRefGoogle Scholar
  39. 39.
    Arroyo S, Kramer G. Treating epilepsy in the elderly: safety considerations. Drug Saf 2001; 24: 991–1015PubMedCrossRefGoogle Scholar
  40. 40.
    Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia 1993; 34: 453–68PubMedCrossRefGoogle Scholar
  41. 41.
    Dam AM, Fuglsang-Frederiksen A, Svarre-Olsen U, et al. Late-onset epilepsy: etiologies, types of seizure, and value of clinical investigation, EEG, and computerized tomography scan. Epilepsia 1985; 26: 227–31PubMedCrossRefGoogle Scholar
  42. 42.
    Forsgren L, Bucht G, Eriksson S, et al. Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study. Epilepsia 1996; 37: 224–9PubMedCrossRefGoogle Scholar
  43. 43.
    Loiseau J, Loiseau P, Duche B, et al. A survey of epileptic disorders in southwest France: seizures in elderly patients. Ann Neurol 1990; 27: 232–7PubMedCrossRefGoogle Scholar
  44. 44.
    Luhdorf K, Jensen LK, Plesner AM. Epilepsy in the elderly: prognosis. Acta Neurol Scand 1986; 74: 409–15PubMedCrossRefGoogle Scholar
  45. 45.
    Forstl H, Burns A, Levy R, et al. Neurologic signs in Alzheimer’s disease: results of a prospective clinical and neuropathologic study. Arch Neurol 1992; 49: 1038–42PubMedCrossRefGoogle Scholar
  46. 46.
    Risse SC, Lampe TH, Bird TD, et al. Myoclonus, seizures and paratonia in Alzheimer’s disease. Alzheimer Dis Assoc Disord 1990; 4: 217–25PubMedCrossRefGoogle Scholar
  47. 47.
    Sulkava R. Alzheimer’s disease and senile dementia of the Alzheimer type: a comparative Study. Acta Neurol Scand 1982; 65: 636–50PubMedCrossRefGoogle Scholar
  48. 48.
    Axelman K, Basun H, Lannfelt L. Wide range of disease onset in a family with Alzheimer disease and a His163Tyrmutation in the presenilin-1 gene. Arch Neurol 1998; 55: 698–702PubMedCrossRefGoogle Scholar
  49. 49.
    Campion D, Flaman JM, Brice A, et al. Mutations of the presenilin I gene in families with early-onset Alzheimer’s disease. Hum Mol Genet 1995; 4: 2373–7PubMedCrossRefGoogle Scholar
  50. 50.
    Kennedy AM, Newman SK, Frackowiak RS, et al. Chromosome 14 linked familial Alzheimer’s disease: a clinico-pathological study of a single pedigree. Brain 1995; 118: 185–205PubMedCrossRefGoogle Scholar
  51. 51.
    Lopera F, Ardilla A, Martinez A, et al. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA 1997; 277: 793–9PubMedCrossRefGoogle Scholar
  52. 52.
    Mangone CA, Castano EM, Levy E, et al. Early onset Alzheimer’s disease in a South American pedigree from Argentina. Acta Neurol Scand 1995; 91: 6–13PubMedGoogle Scholar
  53. 53.
    Fox NC, Kennedy AM, Harvey RJ, et al. Clinicopathological features of familial Alzheimer’s disease associated with the M139V mutation in the presenilin 1 gene: pedigree but not mutation specific age at onset provides evidence for a further genetic factor. Brain 1997; 120: 491–501PubMedCrossRefGoogle Scholar
  54. 54.
    Singleton AB, Hall R, Ballard CG, et al. Pathology of early-onset Alzheimer’s disease cases bearing the Thr113-114ins presenilin-1 mutation. Brain 2000; 123: 2467–74PubMedCrossRefGoogle Scholar
  55. 55.
    Janssen JC, Hall M, Fox NC, et al. Alzheimer’s disease due to an intronic presenilin-1 (PSEN1 intron 4) mutation: a clinicopathological study. Brain 2000; 123: 894–907PubMedCrossRefGoogle Scholar
  56. 56.
    Armon C, Peterson GW, Liwnicz BH. Alzheimer’s disease underlies some cases of complex partial status epilepticus. J Clin Neurophysiol 2000; 17: 511–8PubMedCrossRefGoogle Scholar
  57. 57.
    Kramer G. Epilepsy in the elderly: some clinical and pharmacotherapeutic aspects. Epilepsia 2001; 42Suppl. 3: S55–9CrossRefGoogle Scholar
  58. 58.
    Sirven JI. Management of epilepsy in older adults. Clin Geriatr 2000; 1: 93–9Google Scholar
  59. 59.
    Rabinowicz AL, Starkstein SE, Leiguarda RC, et al. Transient epileptic amnesia in dementia: a treatable unrecognized cause of episodic amnestic wandering. Alzheimer Dis Assoc Disord 2000; 14: 231–3PubMedCrossRefGoogle Scholar
  60. 60.
    Tatum IV WO, Ross J, Cole AJ. Epileptic pseudodementia. Neurology 1998; 50: 1472–5PubMedCrossRefGoogle Scholar
  61. 61.
    Leppik IE, Birnbaum A. Epilepsy in the elderly. Semin Neurol 2002; 22: 309–20PubMedCrossRefGoogle Scholar
  62. 62.
    Kwan P, Brodie MJ. Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet 2001; 357: 216–22PubMedCrossRefGoogle Scholar
  63. 63.
    Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons: predictive model and interrelationship with baseline vulnerability. JAMA 1996; 275: 852–7PubMedCrossRefGoogle Scholar
  64. 64.
    Inouye SK. The dilemma of delirium: clinical and research controversies regarding diagnosis and evaluation of delirium in hospitalized elderly medical patients. Am J Med 1994; 97: 278–88PubMedCrossRefGoogle Scholar
  65. 65.
    Inouye SK, Viscoli CM, Horwitz RI, et al. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993; 119: 474–81PubMedGoogle Scholar
  66. 66.
    Levkoff SE, Evans DA, Liptzin B, et al. Delirium: the occurrence and persistence of symptoms among elderly hospitalized patients. Arch Intern Med 1992; 52: 334–40CrossRefGoogle Scholar
  67. 67.
    Aldenkamp AP. Effects of antiepileptic drugs on cognition. Epilepsia 2001; 42Suppl. 1: 46–9PubMedCrossRefGoogle Scholar
  68. 68.
    Martin R, Meador K, Turrentine L, et al. Comparative cognitive effects of carbamazepine and gabapentin in healthy senior adults. Epilepsia 2001; 42: 764–71PubMedCrossRefGoogle Scholar
  69. 69.
    Farhat G, Yamout B, Mikati MA, et al. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology 2002; 58: 1348–53PubMedCrossRefGoogle Scholar
  70. 70.
    Bowen JD, Larson EB. Drug-induced cognitive impairment: defining the problem and finding the solutions. Drugs Aging 1993; 3: 349–57PubMedCrossRefGoogle Scholar
  71. 71.
    Garnett WR, Carter BL, Pellock JM. Bioavailability of phenytoin administered with antacids. Ther Drug Monit 1979; 1: 435–6CrossRefGoogle Scholar
  72. 72.
    Nation RL, Evans AM, Milne RW. Pharmacokinetic drug interactions with phenytoin: part II. Clin Pharmacokinet 1990; 18: 37–60, 131–150PubMedCrossRefGoogle Scholar
  73. 73.
    Berg MJ, Ebert BE, Rivey MP, et al. Utilization of Km for phenytoin dosage after folate addition to patient’s regimen. Ther Drug Monit 1987; 9: 304–5PubMedCrossRefGoogle Scholar
  74. 74.
    Haley CJ, Nelson J. Phenytoin: enterai feeding interaction. Ann Pharmacother 1989; 23: 796–8Google Scholar
  75. 75.
    French J, Smith M, Faught E, et al. Practice advisory: the use of felbamate in the treatment of patients with intractable epilepsy: report of the Quality Standards of Subcommittee of the American Academy of Neurology and American Epilepsy society. Neurology 1999; 52: 1540–5PubMedCrossRefGoogle Scholar
  76. 76.
    Dodrill CB, Arnett JL, Shu V, et al. Effects of tiagabine monotherapy on abilities, adjustment and mood. Epilepsia 1998; 39: 33–42PubMedCrossRefGoogle Scholar
  77. 77.
    Neyens LG, Alpherts WC, Aldenkamp AP. Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients with epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 1995; 19: 411–9PubMedCrossRefGoogle Scholar
  78. 78.
    Wallace SM, Veerbeeck RK. Plasma protein binding of drugs in the elderly. Clin Pharmacokinet 1987; 12: 41–72PubMedCrossRefGoogle Scholar
  79. 79.
    Piecoro LT, Wermeling DP, Schmitt FA, et al. Seizures in patients receiving concomitant antimuscarinics and acetylcholinesterase inhibitor. Pharmacotherapy 1998; 18: 1129–32PubMedGoogle Scholar
  80. 80.
    Craig I, Tallis R. Impact of valproate and phenytoin on cognitive function in elderly patients: results of a single-blind randomized comparative study. Epilepsia 1994; 35: 381–90PubMedCrossRefGoogle Scholar
  81. 81.
    Duncan JS, Shorvon SD, Trimble MR. Effects of removal of phenytoin, carbamazepine, and valproate on cognitive function. Epilepsia 1990; 31: 584–91PubMedCrossRefGoogle Scholar
  82. 82.
    Bohannon AD, Hanlon JT, Landerman R, et al. Association of race and other potential risk factors with nonvertebral fractures in community-dwelling elderly women. Am J Epidemiol 1999; 149: 1002–9PubMedCrossRefGoogle Scholar
  83. 83.
    Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. N Engl J Med 1992; 327: 765–71PubMedCrossRefGoogle Scholar
  84. 84.
    Chadwick D, Vigabatrin European Monotherapy Study Group. Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study. Lancet 1999; 654: 13–9CrossRefGoogle Scholar
  85. 85.
    Curran HV, Java R. Memory and psychomotor effects of oxcarbazepine in healthy human volunteers. Eur J Clin Pharmacol 1993; 44: 529–33PubMedCrossRefGoogle Scholar
  86. 86.
    Richens A. Clinical pharmacokinetics of gabapentin. In: Chadwick D, editor. New trends in epilepsy management: the role of gabapentin. London: Royal Society of Medicine Services, 1993: 41–6Google Scholar
  87. 87.
    Brodie MJ, Overstall PW, Giorgi L, et al. Multicenter double-blind randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Res 1999; 37: 81–7PubMedCrossRefGoogle Scholar
  88. 88.
    Brodie MJ, French JA. Management of epilepsy in adolescents and adults. Lancet 2000; 356: 323–9PubMedCrossRefGoogle Scholar
  89. 89.
    Peck AW. Clinical pharmacology of lamotrigine. Epilepsia 1991; 32Suppl. 2: S9–S12PubMedCrossRefGoogle Scholar
  90. 90.
    Giorgi L, Gomez G, O’Neill F, et al. The tolerability of lamotrigine in elderly patients with epilepsy. Drugs Aging 2001; 18: 621–30PubMedCrossRefGoogle Scholar
  91. 91.
    Aldenkamp AP, Baker G, Mulder OG, et al. A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures. Epilepsia 2000; 41: 1167–78PubMedCrossRefGoogle Scholar
  92. 92.
    Martin R, Kuzniecky R, Ho S, et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology 1999; 52: 321–7PubMedCrossRefGoogle Scholar
  93. 93.
    Jokeit H, Ebner A. Long term effects of refractory temporal lobe epilepsy on cognitive abilities: a cross sectional study. J Neurol Neurosurg Psychiatry 1999; 67: 44–50PubMedCrossRefGoogle Scholar
  94. 94.
    Samson WN, van Duijn CM, Hop WC, et al. Clinical features and mortality in patients with early-onset Alzheimer’s disease. Eur Neurol 1996; 36: 103–6PubMedCrossRefGoogle Scholar
  95. 95.
    Volicer L, Smith S, Volicer BJ. Effect of seizures on progression of dementia of the Alzheimer type. Dementia 1995; 6: 258–63PubMedGoogle Scholar
  96. 96.
    Hesdorffer DC, Logroscino G, Cascino G, et al. Incidence of status epilepticus in Rochester, Minnesota, 1965–1984. Neurology 1998; 50: 735–41PubMedCrossRefGoogle Scholar
  97. 97.
    Ramsay RE, Pryor F. Epilepsy in the elderly. Neurology 2000; 55Suppl. 1: S9–S14PubMedGoogle Scholar
  98. 98.
    Hauser WA, Rich SS, Lee JR, et al. Risk of recurrent seizures after two unprovoked seizures. N Engl J Med 1998; 338: 429–34PubMedCrossRefGoogle Scholar
  99. 99.
    Rowan AJ. Management of seizures in the elderly. Pharmacotherapy 2000; 20: 178S–84SPubMedCrossRefGoogle Scholar
  100. 100.
    Rowan AJ. Reflections on the treatment of seizures in the elderly population. Neurology 1998, 33Google Scholar
  101. 101.
    Cameron H, Macphee GJ. Anticonvulsant therapy in the elderly: a need for placebo controlled trials. Epilepsy Res 1995; 21: 149–57PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Mario F. Mendez
    • 1
  • Gerald T. H. Lim
    • 1
  1. 1.Department of NeurologyThe University of California at Los AngelesLos AngelesUSA
  2. 2.Neurobehavior (116AF)V.A. Greater Los Angeles Healthcare SystemLos AngelesUSA

Personalised recommendations