Abstract
Patients with dementia have a five- to ten fold increase in risk of seizures, and approximately 12% of new-onset seizures in elderly patients are attributed to degenerative disorders. Likewise, individuals with epilepsy are at an increased risk for developing dementia as an older adult. Due to the high comorbid rates of epilepsy and dementia, it is important for neuropsychologists to understand the bidirectional relationship between dementia and epilepsy. This chapter provides a foundation for understanding the overlap between epilepsy and dementia and provides guidance for diagnostic decision-making and differential diagnosis. Practical tools for clinical assessment are presented as well as a case example.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hesdorffer DC, Beck V, Begley CE, Bishop ML, Cushner-Weinstein S, Holmes GL, et al. Research implications of the Institute of Medicine Report, epilepsy across the spectrum: promoting health and understanding. Epilepsia. 2013;54(2):207–16.
Association As. Alzheimer’s disease facts and figures. Alzheimer’s Dementia. 2017;13:325–73.
Association AP. Diagnostic and statistical manual of mental disorders. Arlington: American Psychiatric Publishing; 2013.
Hommet C, Mondon K, Camus V, De Toffol B, Constans T. Epilepsy and dementia in the elderly. Dement Geriatr Cogn Disord. 2008;25(4):293–300.
Ramsay RE, Rowan AJ, Pryor FM. Special considerations in treating the elderly patient with epilepsy. Neurology. 2004;62(5 suppl 2):S24–S9.
Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475–82.
Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–21.
Mendez MF, Lim GT. Seizures in elderly patients with dementia: epidemiology and management. Drugs Aging. 2003;20(11):791–804.
Brodie MJ, Elder AT, Kwan P. Epilepsy in later life. Lancet Neurol. 2009;8(11):1019–30.
Leppik IE, Birnbaum AK. Epilepsy in the elderly. Ann N Y Acad Sci. 2010;1184(1):208–24.
Leppik IE. Epilepsy in the elderly. Epilepsia. 2006;47(s1):65–70.
Hesdorffer D, Hauser W, Annegers J, Kokmen E, Rocca WA. Dementia and adult-onset unprovoked seizures. Neurology. 1996;46(3):727–30.
Stephen LJ, Brodie MJ. Epilepsy in elderly people. Lancet. 2000;355(9213):1441–6.
Pandis D, Scarmeas N. Seizures in Alzheimer disease: clinical and epidemiological data. Epilepsy Curr. 2012;12(5):184–7.
Sheorajpanday RV, De Deyn PP. Epileptic fits and epilepsy in the elderly: general reflections, specific issues and therapeutic implications. Clin Neurol Neurosurg. 2007;109(9):727–43.
Scarmeas N, Honig LS, Choi H, Cantero J, Brandt J, Blacker D, et al. Seizures in Alzheimer disease: who, when, and how common? Arch Neurol. 2009;66(8):992–7.
Larner A. Epileptic seizures in AD patients. NeuroMolecular Med. 2010;12(1):71–7.
Vossel KA, Tartaglia MC, Nygaard HB, Zeman AZ, Miller BL. Epileptic activity in Alzheimer’s disease: causes and clinical relevance. Lancet Neurol. 2017;16(4):311–22.
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(4):700–7.
Cordonnier C, Henon H, Derambure P, Pasquier F, Leys D. Influence of pre-existing dementia on the risk of post-stroke epileptic seizures. J Neurol Neurosurg Psychiatry. 2005;76(12):1649–53.
Gupta RC, Milatovic D, Dettbarn W-D. Depletion of energy metabolites following acetylcholinesterase inhibitor-induced status epilepticus: protection by antioxidants. Neurotoxicology. 2001;22(2):271–82.
Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012;76(1):116–29.
Gaitatzis A, Carroll K, Majeed A, Sander JW. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia. 2004;45(12):1613–22.
Téllez-Zenteno JF, Matijevic S, Wiebe S. Somatic comorbidity of epilepsy in the general population in Canada. Epilepsia. 2005;46(12):1955–62.
Hermann B, Seidenberg M, Jones J. The neurobehavioural comorbidities of epilepsy: can a natural history be developed? Lancet Neurol. 2008;7(2):151–60.
Vezzani A, Granata T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia. 2005;46(11):1724–43.
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405.
Volicer L, Smith S, Volicer BJ. Effect of seizures on progression of dementia of the Alzheimer type. Dement Geriatr Cogn Disord. 1995;6(5):258–63.
Vossel KA, Beagle AJ, Rabinovici GD, Shu H, Lee SE, Naasan G, et al. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol. 2013;70(9):1158–66.
Rao SC, Dove G, Cascino GD, Petersen RC. Recurrent seizures in patients with dementia: frequency, seizure types, and treatment outcome. Epilepsy Behav. 2009;14(1):118–20.
Helmstaedter C, Kurthen M, Lux S, Reuber M, Elger CE. Chronic epilepsy and cognition: a longitudinal study in temporal lobe epilepsy. Ann Neurol. 2003;54(4):425–32.
Choi H, Pack A, Elkind MS, Longstreth W, Ton TG, Onchiri F. Predictors of incident epilepsy in older adults: the cardiovascular health study. Neurology. 2017;88(9):870–7.
Faught E, Richman J, Martin R, Funkhouser E, Foushee R, Kratt P, et al. Incidence and prevalence of epilepsy among older US Medicare beneficiaries. Neurology. 2012;78(7):448–53.
Hatanpaa KJ, Raisanen JM, Herndon E, Burns DK, Foong C, Habib AA, et al. Hippocampal sclerosis in dementia, epilepsy, and ischemic injury: differential vulnerability of hippocampal subfields. J Neuropathol Exp Neurol. 2014;73(2):136–42.
Mendez MF, Catanzaro P, Doss RC, Arguello R, Frey WH. Seizures in Alzheimer’s disease: clinicopathologic study. J Geriatr Psychiatry Neurol. 1994;7(4):230–3.
Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold K-H, Haass C, et al. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer’s disease. Science. 2008;321(5896):1686–9.
Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fülöp L, et al. Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci. 2009;29(11):3453–62.
Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, et al. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease. Neuron. 2007;55(5):697–711.
Sheng JG, Boop FA, Mrak RE, Griffin WST. Increased neuronal β-amyloid precursor protein expression in human temporal lobe epilepsy: association with interleukin-1α immunoreactivity. J Neurochem. 1994;63(5):1872–9.
García-Cabrero AM, Guerrero-López R, Giráldez BG, Llorens-Martín M, Ávila J, Serratosa JM, et al. Hyperexcitability and epileptic seizures in a model of frontotemporal dementia. Neurobiol Dis. 2013;58:200–8.
Holth JK, Bomben VC, Reed JG, Inoue T, Younkin L, Younkin SG, et al. Tau loss attenuates neuronal network hyperexcitability in mouse and Drosophila genetic models of epilepsy. J Neurosci. 2013;33(4):1651–9.
Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol. 2009;66(4):435–40.
McBride AE, Shih TT, Hirsch LJ. Video-EEG monitoring in the elderly: a review of 94 patients. Epilepsia. 2002;43(2):165–9.
Sheth RD, Drazkowski JF, Sirven JI, Gidal BE, Hermann BP. Protracted ictal confusion in elderly patients. Arch Neurol. 2006;63(4):529–32.
Cloyd J, Hauser W, Towne A, Ramsay R, Mattson R, Gilliam F, et al. Epidemiological and medical aspects of epilepsy in the elderly. Epilepsy Res. 2006;68:39–48.
Ramsay R. Challenges in the diagnosis and treatment of the elderly patient with epilepsy. Ixtapa: Southern Clinical Neurological Society; 2003.
Waterhouse E, Towne A. Seizures in the elderly: nuances in presentation and treatment. Cleve Clin J Med. 2005;72(3):526.
Ito M, Echizenya N, Nemoto D, Kase M. A case series of epilepsy-derived memory impairment resembling Alzheimer disease. Alzheimer Dis Assoc Disord. 2009;23(4):406–9.
Dupont S, Verny M, Harston S, Cartz-Piver L, Schück S, Martin J, et al. Seizures in the elderly: development and validation of a diagnostic algorithm. Epilepsy Res. 2010;89(2):339–48.
Theodore WH. The postictal state: effects of age and underlying brain dysfunction. Epilepsy Behav. 2010;19(2):118–20.
Ramsay RE, Macias FM, Rowan AJ. Diagnosing epilepsy in the elderly. Int Rev Neurobiol. 2007;81:129–51.
Chapin J, Naugle R. Geriatric patients with epilepsy. Handbook on the neuropsychology of epilepsy. New York: Springer; 2015. p. 63–85.
Hauser WA. Seizure disorders: the changes with age. Epilepsia. 1992;33(s4):6–14.
Tinuper P, Provini F, Marini C, Cerullo A, Plazzi G, Avoni P, et al. Partial epilepsy of long duration: changing semiology with age. Epilepsia. 1996;37(2):162–4.
Towne AR. Epidemiology and outcomes of status epilepticus in the elderly. Int Rev Neurobiol. 2007;81:111–27.
Ferro JM, Pinto F. Poststroke epilepsy: epidemiology, pathophysiology and management. Drugs Aging. 2004;21(10):639–54.
Canouï-Poitrine F, Bastuji-Garin S, Alonso E, Darcel G, Verstichel P, Caillet P, et al. Risk and prognostic factors of status epilepticus in the elderly: a case–control study. Epilepsia. 2011;52(10):1849–56.
Tomson T, Walczak T, Sillanpaa M, Sander JW. Sudden unexpected death in epilepsy: a review of incidence and risk factors. Epilepsia. 2005;46(s11):54–61.
Butler CR, Graham KS, Hodges JR, Kapur N, Wardlaw JM, Zeman AZ. The syndrome of transient epileptic amnesia. Ann Neurol. 2007;61(6):587–98.
Nadarajan V, Perry R, Johnson J, Werring D. Transient ischaemic attacks: mimics and chameleons. Pract Neurol. 2014;14(1):23–31.
Bergfeldt L. Differential diagnosis of cardiogenic syncope and seizure disorders. Heart. 2003;89(3):353–8.
Mellers J. The approach to patients with “non-epileptic seizures”. Postgrad Med J. 2005;81(958):498–504.
Malmgren K, Reuber M, Appleton R. Differential diagnosis of epilepsy. In: Oxford textbook of epilepsy and epileptic seizures. Oxford: Oxford University Press; 2012. p. 81–94.
Veran O, Kahane P, Thomas P, Hamelin S, Sabourdy C, Vercueil L. De novo epileptic confusion in the elderly: a 1-year prospective study. Epilepsia. 2010;51(6):1030–5.
Ung K, Larner A. Transient amnesia: epileptic or global? A differential diagnosis with significant implications for management. QJM. 2012;107(11):915–7.
Colman N, Nahm K, Van Dijk J, Reitsma JB, Wa W, Kaufmann H. Diagnostic value of history taking in reflex syncope. Clin Auton Res. 2004;14:i37–44.
Sheldon R. Distinguishing syncope from seizures: how useful is the clinical history? In: Cardiac arrhythmias. Milano: Springer; 2003. 2004.
Bradley M, Boeve F. REM sleep behavior disorder: updated review of the core features, the RBD-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci. 2010;1184:15–54.
Boeve BF, Silber MH, Ferman TJ. REM sleep behavior disorder in Parkinson’s disease and dementia with Lewy bodies. J Geriatr Psychiatry Neurol. 2004;17(3):146–57.
Smith PE. If it’s not epilepsy. J Neurol Neurosurg Psychiatry. 2001;70(suppl 2):ii9–ii14.
Kellinghaus C, Loddenkemper T, Dinner DS, Lachhwani D, O Lüders H. Seizure semiology in the elderly: a video analysis. Epilepsia. 2004;45(3):263–7.
Duncan R, Oto M, Martin E, Pelosi A. Late onset psychogenic nonepileptic attacks. Neurology. 2006;66(11):1644–7.
Bell BD, Giovagnoli AR. Epilepsy and aging. In: Handbook on the neuropsychology of aging and dementia. New York: Springer; 2013. p. 421–41.
Mitsis EM, Bender HA, Kostakoglu L, Machac J, Martin J, Woehr JL, et al. A consecutive case series experience with [18 F] florbetapir PET imaging in an urban dementia center: impact on quality of life, decision making, and disposition. Mol Neurodegener. 2014;9(1):10.
Ettinger AB, Baker GA. Best clinical and research practice in epilepsy of older people: focus on antiepileptic drug adherence. Epilepsy Behav. 2009;15(2):S60–S3.
French JA, Staley BA. AED treatment through different ages: as our brains change, should our drug choices also? Epilepsy Curr. 2012;12(4s):22–7.
Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol. 2003;2(8):473–81.
Lee GP. Neuropsychology of epilepsy and epilepsy surgery. Oxford: Oxford University Press; 2010.
Rowan AJ. Reflections on the treatment of seizures in the elderly population. Neurology. 1998;51(5 Suppl 4):S28–33.
Rowan AJ, Ramsay R, Collins J, Pryor F, Boardman K, Uthman B, et al. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005;64(11):1868–73.
Krumholz A, Wiebe S, Gronseth GS, Gloss DS, Sanchez AM, Kabir AA, et al. Evidence-based guideline: management of an unprovoked first seizure in adults report of the guideline development Subcommittee of the American Academy of neurology and the American Epilepsy Society. Neurology. 2015;84(16):1705–13.
De Reuck J. Management of stroke-related seizures. Acta Neurol Belg. 2009;109(4):271–6.
Mohanraj R, Brodie M. Diagnosing refractory epilepsy: response to sequential treatment schedules. Eur J Neurol. 2006;13(3):277–82.
Acosta I, Vale F, Tatum WO, Benbadis SR. Epilepsy surgery after age 60. Epilepsy Behav. 2008;12(2):324–5.
Grivas A, Schramm J, Kral T, Von Lehe M, Helmstaedter C, Elger CE, et al. Surgical treatment for refractory temporal lobe epilepsy in the elderly: seizure outcome and neuropsychological sequels compared with a younger cohort. Epilepsia. 2006;47(8):1364–72.
Sirven JI, Sperling M, Naritoku D, Schachter S, Labar D, Holmes M, et al. Vagus nerve stimulation therapy for epilepsy in older adults. Neurology. 2000;54(5):1179–82.
Helmstaedter C, Reuber M, Elger CC. Interaction of cognitive aging and memory deficits related to epilepsy surgery. Ann Neurol. 2002;52(1):89–94.
Seeman TE, Lusignolo TM, Albert M, Berkman L. Social relationships, social support, and patterns of cognitive aging in healthy, high-functioning older adults: MacArthur studies of successful aging. Health Psychol. 2001;20(4):243.
Taylor WD. Depression in the elderly. N Engl J Med. 2014;371(13):1228–36.
BUCKS RS, Ashworth D, Wilcock G, Siegfried K. Assessment of activities of daily living in dementia: development of the Bristol Activities of Daily Living Scale. Age Ageing. 1996;25(2):113–20.
Galimberti CA, Magri F, Magnani B, Arbasino C, Cravello L, Marchioni E, et al. Antiepileptic drug use and epileptic seizures in elderly nursing home residents: a survey in the province of Pavia, northern Italy. Epilepsy Res. 2006;68(1):1–8.
Sindi S, Fiocco AJ, Juster RP, Lord C, Pruessner J, Lupien SJ. Now you see it, now you don’t: testing environments modulate the association between hippocampal volume and cortisol levels in young and older adults. Hippocampus. 2014;24(12):1623–32.
Ivnik RJ, Malec JF, Smith GE, Tangalos EG, Petersen RC. Neuropsychological tests’ norms above age 55: COWAT, BNT, MAE token, WRAT-R reading, AMNART, STROOP, TMT, and JLO. Clin Neuropsychol. 1996;10(3):262–78.
Lucas JA, Ivnik RJ, Willis FB, Ferman TJ, Smith GE, Parfitt FC, et al. Mayo’s Older African Americans Normative Studies: normative data for commonly used clinical neuropsychological measures. Clin Neuropsychol. 2005;19(2):162–83.
Nelson HE, Willison J. National adult reading test (NART). Windsor: Nfer-Nelson; 1991.
Wechsler D. Wechsler adult intelligence scale–fourth edition (WAIS–IV), vol. 22. San Antonio: NCS Pearson; 2008. p. 498.
Wechsler D. WASI-II: Wechsler abbreviated scale of intelligence. San Antonio: Psychological Corporation; 2011.
Schmidt M. Rey auditory verbal learning test: a handbook. Los Angeles: Western Psychological Services; 1996.
Benedict R. Brief visual memory test–revised: professional manual. Odessa: Psychological Assessment Resources; 1997.
Meyers JE, Meyers KR. Rey complex figure test and recognition trial professional manual. Odessa: Psychological Assessment Resources; 1995.
Wechsler D. Wechsler memory scale–fourth edition (WMS-IV). San Antonio: Pearson; 2009.
Kaplan E, Goodglass H, Weintraub S. Boston naming test: pro-ed. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2001.
Reitan RM, Wolfson D. The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation. Tucson: Reitan Neuropsychology; 1985.
Heaton R, Chelune G, Talley J, Kay G, Curtiss G. Wisconsin card sorting test manual. Odessa: Psychological Assessment Resources. Inc[Links]; 1981.
Trites R. Grooved pegboard instruction manual. Lafayette: Lafayette Instrument; 1989.
Jurica PJ, Leitten CL, Mattis S. Dementia rating Scale-2: DRS-2: professional manual. Lutz: Psychological Assessment Resources; 2001.
Randolph C. Repeatable battery for the assessment of neuropsychological status (RBANS) update manual. Bloomington: Pearson; 2012.
Kobau R, Gilliam F, Thurman DJ. Prevalence of self-reported epilepsy or seizure disorder and its associations with self-reported depression and anxiety: results from the 2004 Healthstyles Survey. Epilepsia. 2006;47(11):1915–21.
Haut SR, Katz M, Masur J, Lipton RB. Seizures in the elderly: impact on mental status, mood, and sleep. Epilepsy Behav. 2009;14(3):540–4.
Martin RC, Griffith HR, Faught E, Gilliam F, Mackey M, Vogtle L. Cognitive functioning in community dwelling older adults with chronic partial epilepsy. Epilepsia. 2005;46(2):298–303.
Griffith HR, Netson KL, Harrell LE, Zamrini EY, Brockington JC, Marson DC. Amnestic mild cognitive impairment: diagnostic outcomes and clinical prediction over a two-year time period. J Int Neuropsychol Soc. 2006;12(2):166–75.
Paradiso S, Hermann B, Blumer D, Davies K, Robinson R. Impact of depressed mood on neuropsychological status in temporal lobe epilepsy. J Neurol Neurosurg Psychiatry. 2001;70(2):180–5.
Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1983;17(1):37–49.
Pachana NA, Byrne GJ, Siddle H, Koloski N, Harley E, Arnold E. Development and validation of the Geriatric Anxiety Inventory. Int Psychogeriatr. 2007;19(1):103–14.
Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50–5.
Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep. 2004;27(7):1255–73.
Schmutte T, Harris S, Levin R, Zweig R, Katz M, Lipton R. The relation between cognitive functioning and self-reported sleep complaints in nondemented older adults: results from the Bronx aging study. Behav Sleep Med. 2007;5(1):39–56.
Yaffe K, Blackwell T, Barnes D, Ancoli-Israel S, Stone K, Group SoOF. Preclinical cognitive decline and subsequent sleep disturbance in older women. Neurology. 2007;69(3):237–42.
Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.
Martin R, Vogtle L, Gilliam F, Faught E. Health-related quality of life in senior adults with epilepsy: what we know from randomized clinical trials and suggestions for future research. Epilepsy Behav. 2003;4(6):626–34.
Luoni C, Bisulli F, Canevini MP, De Sarro G, Fattore C, Galimberti CA, et al. Determinants of health-related quality of life in pharmacoresistant epilepsy: results from a large multicenter study of consecutively enrolled patients using validated quantitative assessments. Epilepsia. 2011;52(12):2181–91.
Bourdet SV, Gidal BE, Alldredge BK. Pharmacologic management of epilepsy in the elderly. J Am Pharm Assoc (1996). 2001;41(3):421–36.
Vickrey B, Perrine K, Hays R, Hermann B, Cramer J, Meador K, et al. Quality of life in epilepsy QOLIE-31 (version 1.0): scoring manual and patient inventory. Santa Monica: Rand; 1993.
Barr WB, Morrison C. Handbook on the neuropsychology of epilepsy. New York: Springer; 2014.
Chelune GJ, Duff K. The assessment of change: serial assessments in dementia evaluations. In: Handbook on the neuropsychology of aging and dementia. New York: Springer; 2013. p. 43–57.
Acknowledgments
Nicole G. Katz, Psy.D., Lawrence M. Langan and Krithi Ram-Junnarkar.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Coulehan, K., Allison Bender, H. (2019). Evaluation of Comorbid Epilepsy and Dementia. In: Ravdin, L.D., Katzen, H.L. (eds) Handbook on the Neuropsychology of Aging and Dementia. Clinical Handbooks in Neuropsychology. Springer, Cham. https://doi.org/10.1007/978-3-319-93497-6_38
Download citation
DOI: https://doi.org/10.1007/978-3-319-93497-6_38
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-93496-9
Online ISBN: 978-3-319-93497-6
eBook Packages: Behavioral Science and PsychologyBehavioral Science and Psychology (R0)