Background: The reported prevalence of epilepsy in Alzheimer’s disease (AD) is variable, probably due to the different methodological approaches.
Objective: We aimed to define the optimal electroencephalogram (EEG) settings for reliable detection of epileptiform discharges in AD patients.
Methods: We analyzed 24-h EEGs of 5 patients living with AD and epilepsy. The sensitivity of various length EEGs in detecting epileptiform discharges in different periods of the day, the diurnal distribution of the discharges, and their relation to sleep-stages were calculated.
Results: Significant high correlation was identified between the sensitivity of EEG and the length of recordings (r = 0.972, p = 0.005). The sensitivity of a 30-min EEG-epoch recorded between 8:00 and 16:00 was 0.0375 compared to 0.7 between 0:00 and 8:00 (p = 0.005). The average sensitivity of an 8-h EEG-epoch was≥0.8. 82% of epileptiform discharges occurred during sleep, mainly related to non-REM sleep (p < 0.001).
Conclusion: 8-h awake-, or 1-h sleep-EEG provide sufficient sensitivity in detecting epileptiform activity in AD. This needs to be considered in studies on AD-related epilepsy. Recognizing epilepsy in AD patients is essential because it might compromise cognitive functions and accelerate the progression of the disease.
HebertLE, ScherrPA, BieniasJL, BennettDA, EvansDA (2003) Alzheimer disease in the US population: Prevalence estimates using the 2000 census. Arch Neurol60, 1119–1122.
2.
ScarmeasN, HonigLS, ChoiH, CanteroJ, BrandtJ, BlackerD, AlbertM, AmatniekJC, MarderK, BellK, HauserA, SternY (2009) Seizures in Alzheimer disease: Who, when, and how common?Arch Neurol66, 992–997.
3.
DolevI, FogelH, MilshteinH, BardichevskyY, LipsteinN, BroseN, GazitN, SlutskyI (2013) Spike bursts increase amyloid-beta 40/42 ratio by inducing a presenilin-1 conformational change. Nat Neurosci16, 587–595.
4.
HorvathA, SzucsA, BarcsG, NoebelsJL, KamondiA (2016) Epileptic seizures in Alzheimer disease: A review. Alzheimer Dis Assoc Disord30, 186–192.
5.
TreimanDM, WalkerM (2006) Treatment of seizure emergencies: Convulsive and non-convulsive status epilepticus. Epilepsy Res68, 77–82.
6.
NICE-SCIE (2006) Dementia: Supporting people with dementia and their carers in health and social care (NICE Clinical Guideline 42), National Institute for Health and Clinical Excellence and Social Care Institute for Excellence, London.
7.
SmithS (2005) EEG in the diagnosis, classification, and management of patients with epilepsy. J Neurol Neurosurg Psychiatry76(Suppl 2), ii2–ii7.
8.
WestMJ, ColemanPD, FloodDG, TroncosoJC (1994) Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet344, 769–772.
9.
SchuffN, WoernerN, BoretaL, KornfieldT, ShawLM, TrojanowskiJQ, ThompsonPM, JackCR, WeinerMW (2009) MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain132, 1067–1077.
10.
CsuklyG, SirályE, FodorZ, HorváthA, SalaczP, HidasiZ, CsibriÉ, RudasG, SzabóÁ (2016) The differentiation of amnestic type MCI from the Non-amnestic types by structural MRI. Front Aging Neurosci8, 52.
11.
BozzaliM, PadovaniA, CaltagironeC, BorroniB (2011) Regional grey matter loss and brain disconnection across Alzheimer disease evolution. Curr Med Chem18, 2452–2458.
12.
BakkerA, AlbertMS, KraussG, SpeckCL, GallagherM (2015) Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance. Neuroimage Clin7, 688–698.
13.
WangL, ZangY, HeY, LiangM, ZhangX, TianL, WuT, JiangT, LiK (2006) Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: Evidence from resting state fMRI. Neuroimage31, 496–504.
14.
PalopJJ, ChinJ, RobersonED, WangJ, ThwinMT, Bien-LyN, YooJ, HoKO, YuGQ, KreitzerA, FinkbeinerS, NoebelsJL, MuckeL (2007) Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease. Neuron55, 5697–5711.
15.
KissaniN, AlarconG, DadM, BinnieC, PolkeyC (2001) Sensitivity of recordings at sphenoidal electrode site for detecting seizure onset: Evidence from scalp, superficial and deep foramen ovale recordings. Clin Neurophysiol112, 232–240.
16.
NoebelsJ (2011) A perfect storm: Converging paths of epilepsy and Alzheimer’s dementia intersect in the hippocampal formation. Epilepsia52(Suppl 1), 39–46.
17.
BelcastroV, CostaC, GallettiF, PisaniF, CalabresiP, ParnettiL (2007) Levetiracetam monotherapy in Alzheimer patients with late-onset seizures: A prospective observational study. Eur J Neurol14, 1176–1178.
18.
TekinS, Aykut-BingölC, TanridağT, AktanS (1998) Antiglutamatergic therapy in Alzheimer’s disease–effects of lamotrigine. J Neural Transm105, 295–303.
19.
BeyreutherBK, FreitagJ, HeersC, KrebsfängerN, ScharfeneckerU, StöhrT (2007) Lacosamide: A review of preclinical properties. CNS Drug Rev13, 21–42.
20.
CumboE, LigoriLD (2010) Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer’s disease. Epilepsy Behav17, 461–466.
21.
LogarC, WalzlB, LechnerH (1994) Role of long-term EEG monitoring in diagnosis and treatment of epilepsy. Eur J Neurol34(Suppl 1), 29–32.
22.
VosselKA, BeagleAJ, RabinoviciGD, ShuH, LeeSE, NaasanG, HegdeM, CornesSB, HenryML, NelsonAB, SeeleyWW, GeschwindMD, Gorno-TempiniML, ShihT, KirshcHE, GarciaPA, MillerBL, MuckeL (2013) Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol70, 1158–1166.
FisherRS, BoasWVE, BlumeW, ElgerC, GentonP, LeeP, EngelJ (2005) Epileptic seizures and epilepsy: Definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia46, 470–472.
25.
FrisoniGB, FoxNC, JackCR, ScheltensP, ThompsonPM (2010) The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol6, 67–77.
26.
DodrillCB (2002) Progressive cognitive decline in adolescents and adults with epilepsy. Prog Brain Res135, 399–407.
27.
DudasRB, GermanEB, HodgesJR (2005) The Addenbrooke’s cognitiv eexamination (ACE) in the differential diagnosis of early dementias versus affective disorder. Am J Geriatr Psychiatry13, 218–226.
28.
HancockP, LarnerA (2011) Test Your Memory test: Diagnostic utility in a memory clinic population. Int J Geriatr Psychiatry25, 976–980.
29.
TorralvaT, RocaM, GleichgerrchtE, BekinschteinT, ManesF (2009) A neuropsychological battery to detect specific executive and social cognitive impairments in early frontotemporal dementia. Brain132, 1299–1309.
30.
FolsteinMF, FolsteinSE, McHughPR (1975) Mini-mental state: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res12, 189–198.
31.
HorváthA, SzűcsA, KamondiA (2016) Risk factors of Alzheimer’s disease: Depression in the crossfire. JSMAD1, 1000–1009.
32.
SpielbergerCD (2010) State-Trait Anxiety Inventory. John Wiley & Sons, Inc.
33.
BeckAT, SteerRA, BrownGK (1996) Beck Depression Inventory-II. Psychological Corporation, San Antonio TX.
34.
NoachtarS, RémiJ (2009) The role of EEG in epilepsy: A critical review. Epilepsy Behav15, 22–33.
35.
EngelJ (2001) Mesial temporal lobe epilepsy: What have we learned?Neuroscientist7, 340–352.
36.
MoserD, AndererP, GruberG, ParapaticsS, LoretzE, BoeckM, KloeschG, HellerE, SchmidtA, Danker-HopfeH, SaletuB, ZeitlhoferJ, DorffnerG (2009) Sleep classification according to AASM and Rechtschaffen & Kales: Effects on sleep scoring parameters. Sleep32, 139–149.
37.
LalkhenAG, AnthonyM (2008) Clinical tests: Sensitivity and specificity. CEACCP8, 221–223.
38.
SmarrKL, KeeferAL (2011) Measures of depression and depressive symptoms: Beck Depression Inventory-II (BDI-II), Center for Epidemiologic Studies Depression Scale (CES-D), Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9). Arthritis Care Res (Hoboken)63(Suppl 11), 454–466.
39.
HorváthA, MontanaX, LanquartJP, HubainP, Szűcs A, LinkowskiP, LoasG (2016) Effects of state and trait anxiety on sleep structure: A polysomnographic study in 1083 subjects. Psychiatry Res244, 279–283.
40.
KvaalK, UlsteinI, NordhusIH, EngedalK (2005) The Spielberger state-trait anxiety inventory (STAI): The state scale in detecting mental disorders in geriatric patients. Int J Geriatr Psychiatry20, 629–634.
41.
BornH (2015) Seizures in Alzheimer’s disease. Neuroscience286, 251–263.
42.
JelicV, KowalskiJ (2009) Evidence-based evaluation of diagnostic accuracy of resting EEG in dementia and mild cognitive impairment. Clin EEG Neurosci40, 129–142.
43.
SalinskyM, KanterR, DasheiffRM (1987) Effectiveness of multiple EEGs in supporting the diagnosis of epilepsy: An operational curve. Epilepsia28, 331–334.
44.
BinnieC (1996) Epilepsy in adults: Diagnostic EEG investigation. In Recent Advances in Clinical Neurophysiology,KimuraJ, ShibasakiH, eds. Elsevier, Amsterdam, pp. 217–222.
45.
MalowBA, KushwahaR, LinX, MortonKJ, AldrichMS (1997) Relationship of interictal epileptiform discharges to sleep depth in partial epilepsy. Electroencephalogr Clin Neurophysiol102, 20–26.
46.
StabaRJ, WilsonCL, BraginA, JhungD, FriedI, EngelJ (2004) High-frequency oscillations recorded in human medial temporal lobe during sleep. Ann Neurol56, 108–115.
47.
HalaszP, FilakovszkyJ, VarghaA, BagdyG (2002) Effect of sleep deprivation on spikewave discharges in idiopathic generalised epilepsy: A 4×24 hour continuous longterm EEG monitoring study. Epilepsy Res51, 123–132.
48.
AmatniekJC, HauserWA, DelCastillo-CastanedaC, JacobsDM, MarderK, BellK, AlbertM, BrandtJ, SternY (2006) Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia47, 867–872.
49.
AchermannP, DijkD-J, BrunnerDP, BorbélyAA (1993) A model of human sleep homeostasis based on EEG slow-wave activity: Quantitative comparison of data and simulations. Brain Res Bull31, 97–113.
50.
SammaritanoM, GigliGL, GotmanJ (1991) Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy. Neurology41, 290.
