Seizure susceptibility in Alzheimer’s disease
Main Article Content
Abstract
Epileptic seizures in Alzheimer’s disease (AD) patients are rare but still approximately 8 times more common than in the general age-matched population. Experimental and clinical studies have suggested the epileptogenic potential of Aβ, which might represent a principal responsible for the epileptic-like discharges and cognitive decline observed in AD. In addition, an increase in cortical excitability has been demonstrated in AD animal models that may be due to an imbalance of excitatory/inhibitory synaptic transmission. Cortical hyperexcitability has also been demonstrated in the human EEG by the presence of a high proportion of fast oscillatory activities. This review tries to show the mechanisms involved in the generation of the epileptic seizures observed in AD and have been widely studied in animal models. Unfortunately, the EEG analysis in AD is not a standard procedure in clinical practice. Nevertheless, seizures and other electroencephalographic abnormalities are commonly found in AD patients. We suggest that EEG studies in these patients could help to an early diagnosis and inform about the evolution of this disease and their possible cognitive deterioration.
Article Details
How to Cite
REYES-MARIN, Karen E.; ZEGARRA-VALDIVIA, Jonathan A.; NUÑEZ, Angel.
Seizure susceptibility in Alzheimer’s disease.
Medical Research Archives, [S.l.], v. 9, n. 5, may 2021.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2400>. Date accessed: 26 apr. 2024.
doi: https://doi.org/10.18103/mra.v9i5.2400.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Wong W. Economic burden of Alzheimer disease and managed care considerations. Am J Manag Care. 2020;26(8 Suppl):S177-S83.
2. Wittenberg R-, Hu B, Barraza-Araiza L, Funder AR. Projections of older people dementia and costs of dementia care in the United Kingdom 2019-2040 UK2019 [Available from: www.modem-dementia.org.uk.
3. Ferri CP, Jacob KS. Dementia in low-income and middle-income countries: Different realities mandate tailored solutions. PLoS Med. 2017;14(3):e1002271.
4. Malaha AK, Thebaut C, Achille D, Preux PMG, M., editors. Costs of dementia in low-and-middle income countries: a systematic review. 7th International Conference on Neurology and Epidemiology; 2021; Paris, France.
5. Friedman D, Honig LS, Scarmeas N. Seizures and epilepsy in Alzheimer's disease. CNS Neurosci Ther. 2012;18(4):285-94.
6. Norton MC, Clark C, Fauth EB, Piercy KW, Pfister R, Green RC, et al. Caregiver personality predicts rate of cognitive decline in a community sample of persons with Alzheimer's disease. The Cache County Dementia Progression Study. Int Psychogeriatr. 2013;25(10):1629-37.
7. Sloane PD, Zimmerman S, Suchindran C, Reed P, Wang L, Boustani M, et al. The public health impact of Alzheimer's disease, 2000-2050: potential implication of treatment advances. Annu Rev Public Health. 2002;23:213-31.
8. 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.
9. Lesne SE, Sherman MA, Grant M, Kuskowski M, Schneider JA, Bennett DA, et al. Brain amyloid-beta oligomers in ageing and Alzheimer's disease. Brain. 2013;136(Pt 5):1383-98.
10. 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.
11. Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol. 2009;66(4):435-40.
12. Donohue MC, Sperling RA, Petersen R, Sun CK, Weiner MW, Aisen PS, et al. Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons. JAMA. 2017;317(22):2305-16.
13. Insel PS, Mattsson N, Donohue MC, Mackin RS, Aisen PS, Jack CR, Jr., et al. The transitional association between beta-amyloid pathology and regional brain atrophy. Alzheimers Dement. 2015;11(10):1171-9.
14. Dickson DW, Murray ME. Intraneuronal amyloid-beta accumulation in basal forebrain cholinergic neurons: a marker of vulnerability, yet inversely related to neurodegeneration. Brain. 2015;138(Pt 6):1444-5.
15. Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer's disease: Targeting the Cholinergic System. Curr Neuropharmacol. 2016;14(1):101-15.
16. Mesulam MM, Lalehzari N, Rahmani F, Ohm D, Shahidehpour R, Kim G, et al. Cortical cholinergic denervation in primary progressive aphasia with Alzheimer pathology. Neurology. 2019;92(14):e1580-e8.
17. Chaves-Coira I, Martin-Cortecero J, Nunez A, Rodrigo-Angulo ML. Basal Forebrain Nuclei Display Distinct Projecting Pathways and Functional Circuits to Sensory Primary and Prefrontal Cortices in the Rat. Front Neuroanat. 2018;12:69.
18. Zaborszky L. The modular organization of brain systems. Basal forebrain: the last frontier. Prog Brain Res. 2002;136:359-72.
19. Cantero JL, Atienza M, Lage C, Zaborszky L, Vilaplana E, Lopez-Garcia S, et al. Atrophy of Basal Forebrain Initiates with Tau Pathology in Individuals at Risk for Alzheimer's Disease. Cereb Cortex. 2020;30(4):2083-98.
20. Teipel SJ, Meindl T, Grinberg L, Grothe M, Cantero JL, Reiser MF, et al. The cholinergic system in mild cognitive impairment and Alzheimer's disease: an in vivo MRI and DTI study. Hum Brain Mapp. 2011;32(9):1349-62.
21. Born HA. Seizures in Alzheimer's disease. Neuroscience. 2015;286:251-63.
22. Hauser WA, Morris ML, Heston LL, Anderson VE. Seizures and myoclonus in patients with Alzheimer's disease. Neurology. 1986;36(9):1226-30.
23. Liedorp M, Stam CJ, van der Flier WM, Pijnenburg YA, Scheltens P. Prevalence and clinical significance of epileptiform EEG discharges in a large memory clinic cohort. Dement Geriatr Cogn Disord. 2010;29(5):432-7.
24. Amatniek JC, Hauser WA, DelCastillo-Castaneda C, Jacobs DM, Marder K, Bell K, et al. Incidence and predictors of seizures in patients with Alzheimer's disease. Epilepsia. 2006;47(5):867-72.
25. Pandis D, Scarmeas N. Seizures in Alzheimer disease: clinical and epidemiological data. Epilepsy Curr. 2012;12(5):184-7.
26. Vossel KA, Ranasinghe KG, Beagle AJ, Mizuiri D, Honma SM, Dowling AF, et al. Incidence and impact of subclinical epileptiform activity in Alzheimer's disease. Ann Neurol. 2016;80(6):858-70.
27. 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.
28. Rae-Grant A, Blume W, Lau C, Hachinski VC, Fisman M, Merskey H. The electroencephalogram in Alzheimer-type dementia. A sequential study correlating the electroencephalogram with psychometric and quantitative pathologic data. Arch Neurol. 1987;44(1):50-4.
29. Larner AJ. Epileptic seizures in AD patients. Neuromolecular Med. 2010;12(1):71-7.
30. Janssen JC, Beck JA, Campbell TA, Dickinson A, Fox NC, Harvey RJ, et al. Early onset familial Alzheimer's disease: Mutation frequency in 31 families. Neurology. 2003;60(2):235-9.
31. Gueli MC, Taibi G. Alzheimer's disease: amino acid levels and brain metabolic status. Neurol Sci. 2013;34(9):1575-9.
32. Bareggi SR, Franceschi M, Bonini L, Zecca L, Smirne S. Decreased CSF concentrations of homovanillic acid and gamma-aminobutyric acid in Alzheimer's disease. Age- or disease-related modifications? Arch Neurol. 1982;39(11):709-12.
33. Zimmer R, Teelken AW, Trieling WB, Weber W, Weihmayr T, Lauter H. Gamma-aminobutyric acid and homovanillic acid concentration in the CSF of patients with senile dementia of Alzheimer's type. Arch Neurol. 1984;41(6):602-4.
34. Iwakiri M, Mizukami K, Ikonomovic MD, Ishikawa M, Abrahamson EE, DeKosky ST, et al. An immunohistochemical study of GABA A receptor gamma subunits in Alzheimer's disease hippocampus: relationship to neurofibrillary tangle progression. Neuropathology. 2009;29(3):263-9.
35. Mizukami K, Grayson DR, Ikonomovic MD, Sheffield R, Armstrong DM. GABAA receptor beta 2 and beta 3 subunits mRNA in the hippocampal formation of aged human brain with Alzheimer-related neuropathology. Brain Res Mol Brain Res. 1998;56(1-2):268-72.
36. Garcia-Marin V, Blazquez-Llorca L, Rodriguez JR, Boluda S, Muntane G, Ferrer I, et al. Diminished perisomatic GABAergic terminals on cortical neurons adjacent to amyloid plaques. Front Neuroanat. 2009;3:28.
37. Babiloni C, Parra-Rodriguez M. Measures of resting state EEG rhythms for clinical trials in alzheimer’s disease patients: recommendations of an expert panel: Alzheimer’s Dement; 2021 [Available from: https://pureportal.strath.ac.uk/en/publications/measures-of-resting-state-eeg-rhythms-for-clinical-trials-in-alzh.
38. Tait L, Tamagnini F, Stothart G, Barvas E, Monaldini C, Frusciante R, et al. EEG microstate complexity for aiding early diagnosis of Alzheimer's disease. Sci Rep. 2020;10(1):17627.
39. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 2004;13(2):159-70.
40. Reyes-Marin KE, Nunez A. Seizure susceptibility in the APP/PS1 mouse model of Alzheimer's disease and relationship with amyloid beta plaques. Brain Res. 2017;1677:93-100.
41. Westmark CJ, Westmark PR, Beard AM, Hildebrandt SM, Malter JS. Seizure susceptibility and mortality in mice that over-express amyloid precursor protein. Int J Clin Exp Pathol. 2008;1(2):157-68.
42. Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fulop L, et al. Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci. 2009;29(11):3453-62.
43. Chin J, Scharfman HE. Shared cognitive and behavioral impairments in epilepsy and Alzheimer's disease and potential underlying mechanisms. Epilepsy Behav. 2013;26(3):343-51.
44. Chan J, Jones NC, Bush AI, O'Brien TJ, Kwan P. A mouse model of Alzheimer's disease displays increased susceptibility to kindling and seizure-associated death. Epilepsia. 2015;56(6):e73-7.
45. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science. 2007;316(5825):750-4.
46. Gureviciene I, Ishchenko I, Ziyatdinova S, Jin N, Lipponen A, Gurevicius K, et al. Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice. Front Neurol. 2019;10:1151.
47. Del Vecchio RA, Gold LH, Novick SJ, Wong G, Hyde LA. Increased seizure threshold and severity in young transgenic CRND8 mice. Neurosci Lett. 2004;367(2):164-7.
48. Trueba-Saiz A, Cavada C, Fernandez AM, Leon T, Gonzalez DA, Fortea Ormaechea J, et al. Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice. Transl Psychiatry. 2013;3:e330.
49. Cheng CM, Tseng V, Wang J, Wang D, Matyakhina L, Bondy CA. Tau is hyperphosphorylated in the insulin-like growth factor-I null brain. Endocrinology. 2005;146(12):5086-91.
50. Trejo J, Piriz J, Llorens-Martin MV, Fernandez AM, Bolos M, LeRoith D, et al. Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects. Mol Psychiatry. 2007;12(12):1118-28.
51. Carro E, Trejo JL, Spuch C, Bohl D, Heard JM, Torres-Aleman I. Blockade of the insulin-like growth factor I receptor in the choroid plexus originates Alzheimer's-like neuropathology in rodents: new cues into the human disease? Neurobiol Aging. 2006;27(11):1618-31.
52. Zegarra-Valdivia JA, Santi A, Fernandez de Sevilla ME, Nunez A, Torres Aleman I. Serum Insulin-Like Growth Factor I Deficiency Associates to Alzheimer's Disease Co-Morbidities. J Alzheimers Dis. 2019;69(4):979-87.
53. Siskova Z, Justus D, Kaneko H, Friedrichs D, Henneberg N, Beutel T, et al. Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer's disease. Neuron. 2014;84(5):1023-33.
54. Frazzini V, Guarnieri S, Bomba M, Navarra R, Morabito C, Mariggio MA, et al. Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer's disease mouse model. Cell Death Dis. 2016;7:e2100.
55. Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, Slutsky I. Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci. 2009;12(12):1567-76.
56. Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D. Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron. 2009;62(6):788-801.
57. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci. 2007;27(11):2866-75.
58. Silva-Barrat C, Araneda S, Menini C, Champagnat J, Naquet R. Burst generation in neocortical neurons after GABA withdrawal in the rat. J Neurophysiol. 1992;67:715-27.
59. Born HA, Kim JY, Savjani RR, Das P, Dabaghian YA, Guo Q, et al. Genetic suppression of transgenic APP rescues Hypersynchronous network activity in a mouse model of Alzeimer's disease. J Neurosci. 2014;34(11):3826-40.
60. Knafo S, Alonso-Nanclares L, Gonzalez-Soriano J, Merino-Serrais P, Fernaud-Espinosa I, Ferrer I, et al. Widespread changes in dendritic spines in a model of Alzheimer's disease. Cereb Cortex. 2009;19(3):586-92.
61. Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell. 2012;149(3):708-21.
62. Busche MA, Chen X, Henning HA, Reichwald J, Staufenbiel M, Sakmann B, et al. Critical role of soluble amyloid-beta for early hippocampal hyperactivity in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2012;109(22):8740-5.
63. Costa C, Parnetti L, D'Amelio M, Tozzi A, Tantucci M, Romigi A, et al. Epilepsy, amyloid-beta, and D1 dopamine receptors: a possible pathogenetic link? Neurobiol Aging. 2016;48:161-71.
64. 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(5):1148-58.
65. Jyoti A, Plano A, Riedel G, Platt B. EEG, activity, and sleep architecture in a transgenic AbetaPPswe/PSEN1A246E Alzheimer's disease mouse. J Alzheimers Dis. 2010;22(3):873-87.
66. Wang J, Ikonen S, Gurevicius K, van Groen T, Tanila H. Alteration of cortical EEG in mice carrying mutated human APP transgene. Brain Res. 2002;943(2):181-90.
67. Maatuf Y, Stern EA, Slovin H. Abnormal Population Responses in the Somatosensory Cortex of Alzheimer's Disease Model Mice. Sci Rep. 2016;6:24560.
68. Kent BA, Strittmatter SM, Nygaard HB. Sleep and EEG Power Spectral Analysis in Three Transgenic Mouse Models of Alzheimer's Disease: APP/PS1, 3xTgAD, and Tg2576. J Alzheimers Dis. 2018;64(4):1325-36.
69. Jin N, Ziyatdinova S, Gureviciene I, Tanila H. Response of spike-wave discharges in aged APP/PS1 Alzheimer model mice to antiepileptic, metabolic and cholinergic drugs. Sci Rep. 2020;10(1):11851.
70. Amzica F. Physiology of sleep and wakefulness as it relates to the physiology of epilepsy. J Clin Neurophysiol. 2002;19(6):488-503.
71. Amzica F, Steriade M. Electrophysiological correlates of sleep delta waves. Electroencephalogr Clin Neurophysiol. 1998;107(2):69-83.
72. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Jr., Kawas CH, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-9.
73. Garn H, Waser M, Deistler M, Benke T, Dal-Bianco P, Ransmayr G, et al. Quantitative EEG markers relate to Alzheimer's disease severity in the Prospective Dementia Registry Austria (PRODEM). Clin Neurophysiol. 2015;126(3):505-13.
74. Meghdadi AH, Stevanovic Karic M, McConnell M, Rupp G, Richard C, Hamilton J, et al. Resting state EEG biomarkers of cognitive decline associated with Alzheimer's disease and mild cognitive impairment. PLoS One. 2021;16(2):e0244180.
75. Al-Jumeily D, Iram S, Vialatte FB, Fergus P, Hussain A. A novel method of early diagnosis of Alzheimer's disease based on EEG signals. ScientificWorldJournal. 2015;2015:931387.
76. Simpraga S, Alvarez-Jimenez R, Mansvelder HD, van Gerven JMA, Groeneveld GJ, Poil SS, et al. EEG machine learning for accurate detection of cholinergic intervention and Alzheimer's disease. Sci Rep. 2017;7(1):5775.
77. Malek N, Baker MR, Mann C, Greene J. Electroencephalographic markers in dementia. Acta Neurol Scand. 2017;135(4):388-93.
78. Baker M, Akrofi K, Schiffer R, Boyle MW. EEG Patterns in Mild Cognitive Impairment (MCI) Patients. Open Neuroimag J. 2008;2:52-5.
2. Wittenberg R-, Hu B, Barraza-Araiza L, Funder AR. Projections of older people dementia and costs of dementia care in the United Kingdom 2019-2040 UK2019 [Available from: www.modem-dementia.org.uk.
3. Ferri CP, Jacob KS. Dementia in low-income and middle-income countries: Different realities mandate tailored solutions. PLoS Med. 2017;14(3):e1002271.
4. Malaha AK, Thebaut C, Achille D, Preux PMG, M., editors. Costs of dementia in low-and-middle income countries: a systematic review. 7th International Conference on Neurology and Epidemiology; 2021; Paris, France.
5. Friedman D, Honig LS, Scarmeas N. Seizures and epilepsy in Alzheimer's disease. CNS Neurosci Ther. 2012;18(4):285-94.
6. Norton MC, Clark C, Fauth EB, Piercy KW, Pfister R, Green RC, et al. Caregiver personality predicts rate of cognitive decline in a community sample of persons with Alzheimer's disease. The Cache County Dementia Progression Study. Int Psychogeriatr. 2013;25(10):1629-37.
7. Sloane PD, Zimmerman S, Suchindran C, Reed P, Wang L, Boustani M, et al. The public health impact of Alzheimer's disease, 2000-2050: potential implication of treatment advances. Annu Rev Public Health. 2002;23:213-31.
8. 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.
9. Lesne SE, Sherman MA, Grant M, Kuskowski M, Schneider JA, Bennett DA, et al. Brain amyloid-beta oligomers in ageing and Alzheimer's disease. Brain. 2013;136(Pt 5):1383-98.
10. 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.
11. Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol. 2009;66(4):435-40.
12. Donohue MC, Sperling RA, Petersen R, Sun CK, Weiner MW, Aisen PS, et al. Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons. JAMA. 2017;317(22):2305-16.
13. Insel PS, Mattsson N, Donohue MC, Mackin RS, Aisen PS, Jack CR, Jr., et al. The transitional association between beta-amyloid pathology and regional brain atrophy. Alzheimers Dement. 2015;11(10):1171-9.
14. Dickson DW, Murray ME. Intraneuronal amyloid-beta accumulation in basal forebrain cholinergic neurons: a marker of vulnerability, yet inversely related to neurodegeneration. Brain. 2015;138(Pt 6):1444-5.
15. Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer's disease: Targeting the Cholinergic System. Curr Neuropharmacol. 2016;14(1):101-15.
16. Mesulam MM, Lalehzari N, Rahmani F, Ohm D, Shahidehpour R, Kim G, et al. Cortical cholinergic denervation in primary progressive aphasia with Alzheimer pathology. Neurology. 2019;92(14):e1580-e8.
17. Chaves-Coira I, Martin-Cortecero J, Nunez A, Rodrigo-Angulo ML. Basal Forebrain Nuclei Display Distinct Projecting Pathways and Functional Circuits to Sensory Primary and Prefrontal Cortices in the Rat. Front Neuroanat. 2018;12:69.
18. Zaborszky L. The modular organization of brain systems. Basal forebrain: the last frontier. Prog Brain Res. 2002;136:359-72.
19. Cantero JL, Atienza M, Lage C, Zaborszky L, Vilaplana E, Lopez-Garcia S, et al. Atrophy of Basal Forebrain Initiates with Tau Pathology in Individuals at Risk for Alzheimer's Disease. Cereb Cortex. 2020;30(4):2083-98.
20. Teipel SJ, Meindl T, Grinberg L, Grothe M, Cantero JL, Reiser MF, et al. The cholinergic system in mild cognitive impairment and Alzheimer's disease: an in vivo MRI and DTI study. Hum Brain Mapp. 2011;32(9):1349-62.
21. Born HA. Seizures in Alzheimer's disease. Neuroscience. 2015;286:251-63.
22. Hauser WA, Morris ML, Heston LL, Anderson VE. Seizures and myoclonus in patients with Alzheimer's disease. Neurology. 1986;36(9):1226-30.
23. Liedorp M, Stam CJ, van der Flier WM, Pijnenburg YA, Scheltens P. Prevalence and clinical significance of epileptiform EEG discharges in a large memory clinic cohort. Dement Geriatr Cogn Disord. 2010;29(5):432-7.
24. Amatniek JC, Hauser WA, DelCastillo-Castaneda C, Jacobs DM, Marder K, Bell K, et al. Incidence and predictors of seizures in patients with Alzheimer's disease. Epilepsia. 2006;47(5):867-72.
25. Pandis D, Scarmeas N. Seizures in Alzheimer disease: clinical and epidemiological data. Epilepsy Curr. 2012;12(5):184-7.
26. Vossel KA, Ranasinghe KG, Beagle AJ, Mizuiri D, Honma SM, Dowling AF, et al. Incidence and impact of subclinical epileptiform activity in Alzheimer's disease. Ann Neurol. 2016;80(6):858-70.
27. 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.
28. Rae-Grant A, Blume W, Lau C, Hachinski VC, Fisman M, Merskey H. The electroencephalogram in Alzheimer-type dementia. A sequential study correlating the electroencephalogram with psychometric and quantitative pathologic data. Arch Neurol. 1987;44(1):50-4.
29. Larner AJ. Epileptic seizures in AD patients. Neuromolecular Med. 2010;12(1):71-7.
30. Janssen JC, Beck JA, Campbell TA, Dickinson A, Fox NC, Harvey RJ, et al. Early onset familial Alzheimer's disease: Mutation frequency in 31 families. Neurology. 2003;60(2):235-9.
31. Gueli MC, Taibi G. Alzheimer's disease: amino acid levels and brain metabolic status. Neurol Sci. 2013;34(9):1575-9.
32. Bareggi SR, Franceschi M, Bonini L, Zecca L, Smirne S. Decreased CSF concentrations of homovanillic acid and gamma-aminobutyric acid in Alzheimer's disease. Age- or disease-related modifications? Arch Neurol. 1982;39(11):709-12.
33. Zimmer R, Teelken AW, Trieling WB, Weber W, Weihmayr T, Lauter H. Gamma-aminobutyric acid and homovanillic acid concentration in the CSF of patients with senile dementia of Alzheimer's type. Arch Neurol. 1984;41(6):602-4.
34. Iwakiri M, Mizukami K, Ikonomovic MD, Ishikawa M, Abrahamson EE, DeKosky ST, et al. An immunohistochemical study of GABA A receptor gamma subunits in Alzheimer's disease hippocampus: relationship to neurofibrillary tangle progression. Neuropathology. 2009;29(3):263-9.
35. Mizukami K, Grayson DR, Ikonomovic MD, Sheffield R, Armstrong DM. GABAA receptor beta 2 and beta 3 subunits mRNA in the hippocampal formation of aged human brain with Alzheimer-related neuropathology. Brain Res Mol Brain Res. 1998;56(1-2):268-72.
36. Garcia-Marin V, Blazquez-Llorca L, Rodriguez JR, Boluda S, Muntane G, Ferrer I, et al. Diminished perisomatic GABAergic terminals on cortical neurons adjacent to amyloid plaques. Front Neuroanat. 2009;3:28.
37. Babiloni C, Parra-Rodriguez M. Measures of resting state EEG rhythms for clinical trials in alzheimer’s disease patients: recommendations of an expert panel: Alzheimer’s Dement; 2021 [Available from: https://pureportal.strath.ac.uk/en/publications/measures-of-resting-state-eeg-rhythms-for-clinical-trials-in-alzh.
38. Tait L, Tamagnini F, Stothart G, Barvas E, Monaldini C, Frusciante R, et al. EEG microstate complexity for aiding early diagnosis of Alzheimer's disease. Sci Rep. 2020;10(1):17627.
39. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 2004;13(2):159-70.
40. Reyes-Marin KE, Nunez A. Seizure susceptibility in the APP/PS1 mouse model of Alzheimer's disease and relationship with amyloid beta plaques. Brain Res. 2017;1677:93-100.
41. Westmark CJ, Westmark PR, Beard AM, Hildebrandt SM, Malter JS. Seizure susceptibility and mortality in mice that over-express amyloid precursor protein. Int J Clin Exp Pathol. 2008;1(2):157-68.
42. Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fulop L, et al. Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci. 2009;29(11):3453-62.
43. Chin J, Scharfman HE. Shared cognitive and behavioral impairments in epilepsy and Alzheimer's disease and potential underlying mechanisms. Epilepsy Behav. 2013;26(3):343-51.
44. Chan J, Jones NC, Bush AI, O'Brien TJ, Kwan P. A mouse model of Alzheimer's disease displays increased susceptibility to kindling and seizure-associated death. Epilepsia. 2015;56(6):e73-7.
45. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science. 2007;316(5825):750-4.
46. Gureviciene I, Ishchenko I, Ziyatdinova S, Jin N, Lipponen A, Gurevicius K, et al. Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice. Front Neurol. 2019;10:1151.
47. Del Vecchio RA, Gold LH, Novick SJ, Wong G, Hyde LA. Increased seizure threshold and severity in young transgenic CRND8 mice. Neurosci Lett. 2004;367(2):164-7.
48. Trueba-Saiz A, Cavada C, Fernandez AM, Leon T, Gonzalez DA, Fortea Ormaechea J, et al. Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice. Transl Psychiatry. 2013;3:e330.
49. Cheng CM, Tseng V, Wang J, Wang D, Matyakhina L, Bondy CA. Tau is hyperphosphorylated in the insulin-like growth factor-I null brain. Endocrinology. 2005;146(12):5086-91.
50. Trejo J, Piriz J, Llorens-Martin MV, Fernandez AM, Bolos M, LeRoith D, et al. Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects. Mol Psychiatry. 2007;12(12):1118-28.
51. Carro E, Trejo JL, Spuch C, Bohl D, Heard JM, Torres-Aleman I. Blockade of the insulin-like growth factor I receptor in the choroid plexus originates Alzheimer's-like neuropathology in rodents: new cues into the human disease? Neurobiol Aging. 2006;27(11):1618-31.
52. Zegarra-Valdivia JA, Santi A, Fernandez de Sevilla ME, Nunez A, Torres Aleman I. Serum Insulin-Like Growth Factor I Deficiency Associates to Alzheimer's Disease Co-Morbidities. J Alzheimers Dis. 2019;69(4):979-87.
53. Siskova Z, Justus D, Kaneko H, Friedrichs D, Henneberg N, Beutel T, et al. Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer's disease. Neuron. 2014;84(5):1023-33.
54. Frazzini V, Guarnieri S, Bomba M, Navarra R, Morabito C, Mariggio MA, et al. Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer's disease mouse model. Cell Death Dis. 2016;7:e2100.
55. Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, Slutsky I. Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci. 2009;12(12):1567-76.
56. Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D. Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron. 2009;62(6):788-801.
57. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci. 2007;27(11):2866-75.
58. Silva-Barrat C, Araneda S, Menini C, Champagnat J, Naquet R. Burst generation in neocortical neurons after GABA withdrawal in the rat. J Neurophysiol. 1992;67:715-27.
59. Born HA, Kim JY, Savjani RR, Das P, Dabaghian YA, Guo Q, et al. Genetic suppression of transgenic APP rescues Hypersynchronous network activity in a mouse model of Alzeimer's disease. J Neurosci. 2014;34(11):3826-40.
60. Knafo S, Alonso-Nanclares L, Gonzalez-Soriano J, Merino-Serrais P, Fernaud-Espinosa I, Ferrer I, et al. Widespread changes in dendritic spines in a model of Alzheimer's disease. Cereb Cortex. 2009;19(3):586-92.
61. Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell. 2012;149(3):708-21.
62. Busche MA, Chen X, Henning HA, Reichwald J, Staufenbiel M, Sakmann B, et al. Critical role of soluble amyloid-beta for early hippocampal hyperactivity in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2012;109(22):8740-5.
63. Costa C, Parnetti L, D'Amelio M, Tozzi A, Tantucci M, Romigi A, et al. Epilepsy, amyloid-beta, and D1 dopamine receptors: a possible pathogenetic link? Neurobiol Aging. 2016;48:161-71.
64. 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(5):1148-58.
65. Jyoti A, Plano A, Riedel G, Platt B. EEG, activity, and sleep architecture in a transgenic AbetaPPswe/PSEN1A246E Alzheimer's disease mouse. J Alzheimers Dis. 2010;22(3):873-87.
66. Wang J, Ikonen S, Gurevicius K, van Groen T, Tanila H. Alteration of cortical EEG in mice carrying mutated human APP transgene. Brain Res. 2002;943(2):181-90.
67. Maatuf Y, Stern EA, Slovin H. Abnormal Population Responses in the Somatosensory Cortex of Alzheimer's Disease Model Mice. Sci Rep. 2016;6:24560.
68. Kent BA, Strittmatter SM, Nygaard HB. Sleep and EEG Power Spectral Analysis in Three Transgenic Mouse Models of Alzheimer's Disease: APP/PS1, 3xTgAD, and Tg2576. J Alzheimers Dis. 2018;64(4):1325-36.
69. Jin N, Ziyatdinova S, Gureviciene I, Tanila H. Response of spike-wave discharges in aged APP/PS1 Alzheimer model mice to antiepileptic, metabolic and cholinergic drugs. Sci Rep. 2020;10(1):11851.
70. Amzica F. Physiology of sleep and wakefulness as it relates to the physiology of epilepsy. J Clin Neurophysiol. 2002;19(6):488-503.
71. Amzica F, Steriade M. Electrophysiological correlates of sleep delta waves. Electroencephalogr Clin Neurophysiol. 1998;107(2):69-83.
72. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Jr., Kawas CH, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-9.
73. Garn H, Waser M, Deistler M, Benke T, Dal-Bianco P, Ransmayr G, et al. Quantitative EEG markers relate to Alzheimer's disease severity in the Prospective Dementia Registry Austria (PRODEM). Clin Neurophysiol. 2015;126(3):505-13.
74. Meghdadi AH, Stevanovic Karic M, McConnell M, Rupp G, Richard C, Hamilton J, et al. Resting state EEG biomarkers of cognitive decline associated with Alzheimer's disease and mild cognitive impairment. PLoS One. 2021;16(2):e0244180.
75. Al-Jumeily D, Iram S, Vialatte FB, Fergus P, Hussain A. A novel method of early diagnosis of Alzheimer's disease based on EEG signals. ScientificWorldJournal. 2015;2015:931387.
76. Simpraga S, Alvarez-Jimenez R, Mansvelder HD, van Gerven JMA, Groeneveld GJ, Poil SS, et al. EEG machine learning for accurate detection of cholinergic intervention and Alzheimer's disease. Sci Rep. 2017;7(1):5775.
77. Malek N, Baker MR, Mann C, Greene J. Electroencephalographic markers in dementia. Acta Neurol Scand. 2017;135(4):388-93.
78. Baker M, Akrofi K, Schiffer R, Boyle MW. EEG Patterns in Mild Cognitive Impairment (MCI) Patients. Open Neuroimag J. 2008;2:52-5.