The implications of frailty in older adults with epilepsy.
epilepsy
frailty
older adults
seizure
Journal
Epilepsia open
ISSN: 2470-9239
Titre abrégé: Epilepsia Open
Pays: United States
ID NLM: 101692036
Informations de publication
Date de publication:
09 Sep 2024
09 Sep 2024
Historique:
revised:
15
08
2024
received:
17
07
2024
accepted:
29
08
2024
medline:
9
9
2024
pubmed:
9
9
2024
entrez:
9
9
2024
Statut:
aheadofprint
Résumé
Older adults constitute a large proportion of people with epilepsy (PWE) due to the changing demographics worldwide and epilepsy's natural history. Aging-related pathophysiological changes lower the tolerance and increase our vulnerability to stressors, which manifests as frailty. Frailty is closely associated with adverse health outcomes. This narrative review examines the interplay between frailty and epilepsy, especially in older adults, emphasizing its clinical implications, including its role in managing PWE. Mechanistically, frailty develops through complex interactions among molecular and cellular damage, including genomic instability, mitochondrial dysfunction, and hormonal changes. These contribute to systemic muscle mass, bone density, and organ function decline. The concept of frailty has evolved from a primarily physical syndrome to include social, psychological, and cognitive dimensions. The "phenotypic frailty" model, which focuses on physical performance, and the "deficit accumulation" model, which quantifies health deficits, provide frameworks for understanding and assessing frailty. PWE are potentially more prone to developing frailty due to a higher prevalence of risk factors predisposing to frailty. These include, but are not limited to, polypharmacy, higher comorbidity, low exercise level, social isolation, low vitamin D, and osteoporosis. We lack commercial biomarkers to measure frailty but can diagnose it using self- or healthcare provider-administered frailty scales. Recent attempts to develop a PWE-specific frailty scale are promising. Unlike chronological age, frailty is reversible, so its management using multidisciplinary care teams should be strongly considered. Frailty can affect antiseizure medication (ASM) tolerance secondary to its impact on pharmacokinetics and pharmacodynamics. While frailty's effect on seizure control efficacy of ASM is poorly understood, its undoubted association with overall poor outcomes, including epilepsy surgery, behooves us to consider its presence and implication while treating older PWE. Incorporation of frailty measures in future research is essential to improve our understanding of frailty's role in PWE health. PLAIN LANGUAGE SUMMARY: Frailty is the declining state of the human body. People with epilepsy are more prone to it. It should be factored into their management.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
Références
Powell JL. The power of global aging. Ageing Int. 2010;35(1):1–14.
Niccoli T, Partridge L. Ageing as a risk factor for disease. Curr Biol. 2012;22(17):R741–R752.
Merriam‐Webster. Available from: www.merriam‐webster.com
WHO. WHO Clinical Consortium on Healthy Ageing Topic Focus: Frailty and Intrinsic Capacity. 2016.
Dent E, Martin FC, Bergman H, Woo J, Romero‐Ortuno R, Walston JD. Management of frailty: opportunities, challenges, and future directions. Lancet. 2019;394(10206):1376–1386.
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.
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–M157.
Gephine S, Mucci P, Grosbois J‐M, Maltais F, Saey D. Physical frailty in COPD patients with chronic respiratory failure. Int J Chron Obstruct Pulmon Dis. 2021;16:1381–1392.
Clegg A, Bates C, Young J, Ryan R, Nichols L, Ann Teale E, et al. Development and validation of an electronic frailty index using routine primary care electronic health record data. Age Ageing. 2016;45(3):353–360.
Rolfson DB, Majumdar SR, Tsuyuki RT, Tahir A, Rockwood K. Validity and reliability of the Edmonton frail scale. Age Ageing. 2006;35(5):526–529.
Fried LP, Cohen AA, Xue Q‐L, Walston J, Bandeen‐Roche K, Varadhan R. The physical frailty syndrome as a transition from homeostatic symphony to cacophony. Nature Aging. 2021;1(1):36–46.
Rockwood K, Mitnitski A. Frailty, fitness, and the mathematics of deficit accumulation. Rev Clin Gerontol. 2007;17(1):1–12.
Song X, Mitnitski A, Rockwood K. Prevalence and 10‐year outcomes of frailty in older adults in relation to deficit accumulation. J Am Geriatr Soc. 2010;58(4):681–687.
Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62(7):722–727.
Estes EM, Rumalla K, Kazim SF, Kassicieh AJ, Segura AC, Kogan M, et al. Frailty measured by the risk analysis index predicts nonhome discharge and mortality after resection in refractory epilepsy: analysis of 1236 patients from a prospective surgical registry, 2012 to 2020. Neurosurgery. 2022;10:1227.
Vernerey D, Anota A, Vandel P, Paget‐Bailly S, Dion M, Bailly V, et al. Development and validation of the FRAGIRE tool for assessment an older person's risk for frailty. BMC Geriatr. 2016;16:1–28.
Cerulli Irelli E, Borioni MS, Morano A, Mazzeo A, Moro P, Orlando B, et al. Frailty as a comprehensive health measure beyond seizure control in patients with epilepsy: a cross‐sectional study. Epilepsia. 2024;65:1658–1667.
Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173(5):489–495.
Green SF, Loefflad N, Heaney DC, Rajakulendran S. New‐onset seizures in older people: clinical features, course and outcomes. J Neurol Sci. 2021;429:118065.
Morley JE, Vellas B, Van Kan GA, Anker SD, Bauer JM, Bernabei R, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392–397.
Pilotto A, Ferrucci L, Franceschi M, D'Ambrosio LP, Scarcelli C, Cascavilla L, et al. Development and validation of a multidimensional prognostic index for one‐year mortality from comprehensive geriatric assessment in hospitalized older patients. Rejuvenation Res. 2008;11(1):151–161.
Gilbert T, Neuburger J, Kraindler J, Keeble E, Smith P, Ariti C, et al. Development and validation of a hospital frailty risk score focusing on older people in acute care settings using electronic hospital records: an observational study. Lancet. 2018;391(10132):1775–1782.
De Witte N, Gobbens R, De Donder L, Dury S, Buffel T, Schols J, et al. The comprehensive frailty assessment instrument: development, validity and reliability. Geriatr Nurs. 2013;34(4):274–281.
Aunan J, Watson M, Hagland H, Søreide K. Molecular and biological hallmarks of ageing. J Br Surg. 2016;103(2):e29–e46.
Musso CG, Jauregui JR, Macías Núñez JF. Frailty phenotype and chronic kidney disease: a review of the literature. Int Urol Nephrol. 2015;47:1801–1807.
Chen Y, Nagib MM, Yasmen N, Sluter MN, Littlejohn TL, Yu Y, et al. Neuroinflammatory mediators in acquired epilepsy: an update. Inflamm Res. 2023;72(4):683–701.
Punia V, Bhansali S, Tsai C. Late‐onset epilepsy clinic: from clinical diagnostics to biomarkers. Seizure: European J Epilepsy. 2024. doi: 10.1016/j.seizure.2024.06.026. Epub ahead of print.
Waldbaum S, Patel M. Mitochondria, oxidative stress, and temporal lobe epilepsy. Epilepsy Res. 2010;88(1):23–45.
Mitnitski A, Collerton J, Martin‐Ruiz C, Jagger C, von Zglinicki T, Rockwood K, et al. Age‐related frailty and its association with biological markers of ageing. BMC Med. 2015;13(1):1–9.
Cardoso AL, Fernandes A, Aguilar‐Pimentel JA, de Angelis MH, Guedes JR, Brito MA, et al. Towards frailty biomarkers: candidates from genes and pathways regulated in aging and age‐related diseases. Ageing Res Rev. 2018;47:214–277.
Kolle AT, Lewis KB, Lalonde M, Backman C. Reversing frailty in older adults: a scoping review. BMC Geriatr. 2023;23(1):751.
Wang X, Hu J, Wu D. Risk factors for frailty in older adults. Medicine. 2022;101(34):e30169.
Oudbier SJ, Goh J, Looijaard SMLM, Reijnierse EM, Meskers CGM, Maier AB. Pathophysiological mechanisms explaining the association between low skeletal muscle mass and cognitive function. J Gerontol: Series A. 2022;77(10):1959–1968.
Santos‐Orlandi AA, Brigola AG, Ottaviani AC, Luchesi BM, Souza ÉN, Moura FG, et al. Elderly caregivers of the elderly: frailty, loneliness and depressive symptoms. Rev Bras Enferm. 2019;72(suppl 2):88–96.
Perucca E, Kwan P. Overtreatment in epilepsy: how it occurs and how it can be avoided. CNS Drugs. 2005;19:897–908.
Mintzer S, Maio V, Foley K. Use of antiepileptic drugs and lipid‐lowering agents in the United States. Epilepsy Behav. 2014;34:105–108.
Haris A, Bachour K, Hopkins RB, Tarride J‐E, Keezer MR. The treatment of epilepsy in younger and older adults: demographic differences and prescribing patterns of anti‐seizure medications in Canada. Epilepsy Res. 2022;184:106941.
Howlett SE, Rutenberg AD, Rockwood K. The degree of frailty as a translational measure of health in aging. Nature Aging. 2021;1(8):651–665.
Punia V. Start low and go slow: the general principle of managing older adults with epilepsy finds robust support from frailty. Epilepsy Currents. 2023;23(4):235–237.
Faller JW, Pereira DN, de Souza S, Nampo FK, Orlandi FS, Matumoto S. Instruments for the detection of frailty syndrome in older adults: a systematic review. PLoS One. 2019;14(4):e0216166.
Subota A, Jetté N, Josephson CB, McMillan J, Keezer MR, Gonzalez‐Izquierdo A, et al. Risk factors for dementia development, frailty, and mortality in older adults with epilepsy–a population‐based analysis. Epilepsy Behav. 2021;120:108006.
Estes EM, Rumalla K, Kazim SF, Kassicieh AJ, Segura AC, Kogan M, et al. Frailty measured by the risk analysis index predicts nonhome discharge and mortality after resection in refractory epilepsy: analysis of 1236 patients from a prospective surgical registry, 2012 to 2020. Neurosurgery. 2023;93(2):267–273.
Vary‐O'Neal A, Miranzadeh S, Husein N, Holroyd‐Leduc J, Sajobi TT, Wiebe S, et al. Association between frailty and antiseizure medication tolerability in older adults with epilepsy. Neurology. 2023;100(11):e1135–e1147.
Ofori‐Asenso R, Chin KL, Mazidi M, Zomer E, Ilomaki J, Zullo AR, et al. Global incidence of frailty and prefrailty among community‐dwelling older adults: a systematic review and meta‐analysis. JAMA Netw Open. 2019;2(8):e198398.
Bandeen‐Roche K, Seplaki CL, Huang J, Buta B, Kalyani RR, Varadhan R, et al. Frailty in older adults: a nationally representative profile in the United States. J Gerontol A Biol Sci Med Sci. 2015;70(11):1427–1434.
O'Caoimh R, Sezgin D, O'Donovan MR, Molloy DW, Clegg A, Rockwood K, et al. Prevalence of frailty in 62 countries across the world: a systematic review and meta‐analysis of population‐level studies. Age Ageing. 2021;50(1):96–104.
Zawar I. Epilepsy, cardiovascular risks, and dementia: a ménage à trois. Epilepsy Currents. 2023;23(5):283–285.
Johnson EL, Krauss GL, Lee AK, Schneider AL, Dearborn JL, Kucharska‐Newton AM, et al. Association between midlife risk factors and late‐onset epilepsy: results from the atherosclerosis risk in communities study. JAMA Neurol. 2018;75(11):1375–1382.
Tinetti ME, Han L, Lee DS, McAvay GJ, Peduzzi P, Gross CP, et al. Antihypertensive medications and serious fall injuries in a nationally representative sample of older adults. JAMA Intern Med. 2014;174(4):588–595.
Chang C‐S, Liao C‐H, Lin C‐C, Lane H‐Y, Sung F‐C, Kao C‐H. Patients with epilepsy are at an increased risk of subsequent stroke: a population‐based cohort study. Seizure. 2014;23(5):377–381.
Burton JK, Stewart J, Blair M, Oxley S, Wass A, Taylor‐Rowan M, et al. Prevalence and implications of frailty in acute stroke: systematic review & meta‐analysis. Age Ageing. 2022;51(3):afac064.
Nader MM, Cosarderelioglu C, Miao E, Whitson H, Xue Q‐L, Grodstein F, et al. Navigating and diagnosing cognitive frailty in research and clinical domains. Nature Aging. 2023;3(11):1325–1333.
Kaestner E, Reyes A, Chen A, Rao J, Macari AC, Choi JY, et al. Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment. Brain. 2021;144(1):236–250.
Kulmala J, Nykänen I, Mänty M, Hartikainen S. Association between frailty and dementia: a population‐based study. Gerontology. 2013;60(1):16–21.
Tai XY, Torzillo E, Lyall DM, Manohar S, Husain M, Sen A. Association of dementia risk with focal epilepsy and modifiable cardiovascular risk factors. JAMA Neurol. 2023;80(5):445–454.
Zawar I, Kapur J. Does Alzheimer's disease with mesial temporal lobe epilepsy represent a distinct disease subtype? Alzheimers Dement. 2023;19(6):2697–2706.
Rost NS, Brodtmann A, Pase MP, van Veluw SJ, Biffi A, Duering M, et al. Post‐stroke cognitive impairment and dementia. Circ Res. 2022;130(8):1252–1271.
Galovic M, Ferreira‐Atuesta C, Abraira L, Döhler N, Sinka L, Brigo F, et al. Seizures and epilepsy after stroke: epidemiology, biomarkers and management. Drugs Aging. 2021;38:285–299.
Thurman DJ, Begley CE, Carpio A, Helmers S, Hesdorffer DC, Mu J, et al. The primary prevention of epilepsy: a report of the prevention task force of the international league against epilepsy. Epilepsia. 2018;59(5):905–914.
Pollock L, Smith M. Frailty for neurologists: a practical guide. Pract Neurol. 2021;21(6):468–474.
Puig Campmany M, Ris Romeu J, Blázquez Andión M, Benito VS. Development of a comprehensive, multidisciplinary program of care for frailty in an emergency department. Eur Geriatr Med. 2019;10:37–46.
Hendry A, Vanhecke E, Carriazo A, Lopez‐Samaniego L, Espinosa JM, Sezgin D, et al. Integrated care models for managing and preventing frailty: a systematic review for the European joint action on frailty prevention (ADVANTAGE JA). Transl Med UniSa. 2019;19:5.
Robert Allison I, Assadzandi S, Adelman M. Frailty: evaluation and management. Am Fam Physician. 2021;103(4):219–226.
Zheng L, Li G, Qiu Y, Wang C, Wang C, Chen L. Clinical practice guidelines for the prevention and management of frailty: a systematic review. J Adv Nurs. 2022;78(3):709–721.
Divino V, Petrilla AA, Bollu V, Velez F, Ettinger A, Makin C. Clinical and economic burden of breakthrough seizures. Epilepsy Behav. 2015;51:40–47.
Boucher EL, Gan JM, Rothwell PM, Shepperd S, Pendlebury ST. Prevalence and outcomes of frailty in unplanned hospital admissions: a systematic review and meta‐analysis of hospital‐wide and general (internal) medicine cohorts. EClinicalMedicine. 2023;59:101947.
Gutiérrez‐Valencia M, Izquierdo M, Cesari M, Casas‐Herrero Á, Inzitari M, Martínez‐Velilla N. The relationship between frailty and polypharmacy in older people: a systematic review. Br J Clin Pharmacol. 2018;84(7):1432–1444.
Bernus I, Dickinson RG, Hooper WD, Eadie MJ. Anticonvulsant therapy in aged patients: clinical pharmacokinetic considerations. Drugs Aging. 1997;10:278–289.
Perucca E, Berlowitz D, Birnbaum A, Cloyd JC, Garrard J, Hanlon J, et al. Pharmacological and clinical aspects of antiepileptic drug use in the elderly. Epilepsy Res. 2006;68:49–63.
Hilmer SN, Wu H, Zhang M. Biology of frailty: implications for clinical pharmacology and drug therapy in frail older people. Mech Ageing Dev. 2019;181:22–28.
Lezaic N, Gore G, Josephson CB, Wiebe S, Jetté N, Keezer MR. The medical treatment of epilepsy in the elderly: a systematic review and meta‐analysis. Epilepsia. 2019;60(7):1325–1340.
Lattanzi S, Trinka E, Del Giovane C, Nardone R, Silvestrini M, Brigo F. Antiepileptic drug monotherapy for epilepsy in the elderly: a systematic review and network meta‐analysis. Epilepsia. 2019;60(11):2245–2254.
Husein N, Langlois‐Thérien T, Rioux B, Josephson CB, Jetté N, Keezer MR. Medical and surgical treatment of epilepsy in older adults: a national survey. Epilepsia. 2023;64(4):900–909.
Gielen E, Dupont J, Dejaeger M, Laurent MR. Sarcopenia, osteoporosis and frailty. Metabolism. 2023;145:155638.
Johnson EC, Helen Cross J, Reilly C. Physical activity in people with epilepsy: a systematic review. Epilepsia. 2020;61(6):1062–1081.
Josephson CB, Gonzalez‐Izquierdo A, Denaxas S, Sajobi TT, Klein KM, Wiebe S. Independent associations of incident epilepsy and enzyme‐inducing and non–enzyme‐inducing Antiseizure medications with the development of osteoporosis. JAMA Neurol. 2023;80(8):843–850.
Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with use of antiepileptic drugs. Epilepsia. 2004;45(11):1330–1337.
Song Y, Wu Z, Huo H, Zhao P. The impact of frailty on adverse outcomes in geriatric hip fracture patients: a systematic review and meta‐analysis. Front Public Health. 2022;10:890652.
Sheth RD, Harden CL. Screening for bone health in epilepsy. Epilepsia. 2007;48:39–41.
Mendez MF, Lim GT. Seizures in elderly patients with dementia: epidemiology and management. Drugs Aging. 2003;20:791–803.
Arif H, Buchsbaum R, Weintraub D, Pierro J, Resor SR Jr, Hirsch LJ. Patient‐reported cognitive side effects of antiepileptic drugs: predictors and comparison of all commonly used antiepileptic drugs. Epilepsy Behav. 2009;14(1):202–209.
Siniscalchi A, Gallelli L, Russo E, De Sarro G. A review on antiepileptic drugs‐dependent fatigue: pathophysiological mechanisms and incidence. Eur J Pharmacol. 2013;718(1–3):10–16.
Piccenna L, O'Dwyer R, Leppik I, Beghi E, Giussani G, Costa C, et al. Management of epilepsy in older adults: a critical review by the ILAE task force on epilepsy in the elderly. Epilepsia. 2023;64(3):567–585.
Piazzini A, Canevini MP, Turner K, Chifari R, Canger R. Elderly people and epilepsy: cognitive function. Epilepsia. 2006;47:82–84.
Bartolini E, Ferrari AR, Lattanzi S, Pradella S, Zaccara G. Drug‐resistant epilepsy at the age extremes: disentangling the underlying etiology. Epilepsy Behav. 2022;132:108739.
Sarkis RA, Beers L, Farah E, Al‐Akaidi M, Zhang Y, Locascio JJ, et al. The neurophysiology and seizure outcomes of late onset unexplained epilepsy. Clin Neurophysiol. 2020;131(11):2667–2672.
Punia V, Abdelkader A, Busch RM, Gonzalez‐Martinez J, Bingaman W, Najm I, et al. Time to push the age limit: epilepsy surgery in patients 60 years or older. Epilepsia Open. 2018;3(1):73–80.
Punia V, Abdelkader A, Stojic A. Breaking the age barrier: epilepsy surgery in septuagenarians. Epilepsy Behav. 2017;70:94–96.
Hwang G, Hermann B, Nair VA, Conant LL, Dabbs K, Mathis J, et al. Brain aging in temporal lobe epilepsy: chronological, structural, and functional. NeuroImage: Clinical. 2020;25:102183.
Caciagli L, Bernasconi A, Wiebe S, Koepp MJ, Bernasconi N, Bernhardt BC. A meta‐analysis on progressive atrophy in intractable temporal lobe epilepsy: time is brain? Neurology. 2017;89(5):506–516.
Galovic M, van Dooren VQ, Postma TS, Vos SB, Caciagli L, Borzì G, et al. Progressive cortical thinning in patients with focal epilepsy. JAMA Neurol. 2019;76(10):1230–1239.
Estes EM, Asserson DB, Kazim SF, Kogan M, Rumalla K, Spader HS, et al. Baseline frailty status, not advanced patient age, predicts epilepsy surgery outcomes: an analysis of 696 patients from the NSQIP database. Clin Neurol Neurosurg. 2023;231:107864.