Treatment of epilepsy in patients with Alzheimer’s disease

Giorgi, Filippo Sean; Guida, Melania; Vergallo, Andrea; Bonuccelli, Ubaldo; Zaccara, Gaetano

doi:10.1080/14737175.2017.1243469

Cited by 22 publications

(21 citation statements)

References 95 publications

(107 reference statements)

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“…Treatment of seizures in AD with low-dose antiepileptic drugs (AEDs) is usually well tolerated and efficacious, and selected AEDs might also help in slowing-down disease progression [269,270]. Anticonvulsants may suppress seizures in up to two-thirds of all patients, with no apparent effects on long-term prognosis [271].…”

Section: Epilepsymentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6–10 drugs/day with the consequent risk for drug–drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.

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Section: Epilepsymentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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“…Our findings have clinical implications, because older persons and especially persons with AD may be susceptible to the adverse effects and events of older AEDs [ 6, 7 ] and, moreover, to cognitive and motor impairments [ 31–33 ]. Old AEDs such as carbamazepine have a narrow therapeutic window and multiple potential pharmacokinetic drug-drug interactions [ 34, 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, there are no previous studies concerning the AED utilization patterns with the focus on the incidence and prevalence in relation to AD diagnosis. AED use in persons with AD or other dementive disorders is related to higher risk of adverse drug effects and drug-drug interactions especially in the case of older antiepileptics [ 6, 7 ].…”

Section: Introductionmentioning

confidence: 99%

Incidence and Prevalence of Antiepileptic Medication Use in Community-Dwelling Persons with and without Alzheimer’s Disease

Sarycheva

Taipale

Lavikainen

et al. 2018

JAD

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Background:Although antiepileptic drugs (AEDs) have a potential for adverse drug reactions in older populations, little is known about their use in relation to Alzheimer’s disease (AD) diagnosis.Objectives:In this study, we investigated the incidence and prevalence of AED use in relation to AD diagnosis.Methods:The MEDALZ–study includes all Finnish persons who received clinically verified AD diagnoses (n = 70,718) during 2005–2011 and a matched comparison cohort without AD (n = 70,718). AD diagnoses were identified from the Special Reimbursement Register. We used the Prescription Register to identify dispensed AEDs. Incident AED users were identified with a one-year washout period 9-10 years before AD diagnosis, and incidence rates per 100 person-years were calculated for each six-month period from nine years before to five years after AD diagnosis. Prevalence was assessed as proportion using AEDs during each six-month time period for incident use.Results:Persons with AD were more likely to use AEDs during the study period (4.3%) than persons without AD (3.2%). The incidence and prevalence of AED use was higher among persons with AD and increased around the time of AD diagnosis. Epilepsy diagnoses did not explain these differences. Persons with AD were more likely to use older AEDs.Conclusion:Our study highlights the need to balance effective symptom control with the possible risks of treatment.

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“…Tremendous efforts have been made to develop effective drugs for AD. Epilepsy is significantly more frequent in AD patients than in age‐matched controls . Levetiracetam, an antiepileptic drug, decreased epileptiform activity, resulting in improved learning and memory without changes in Aβ levels .…”

Section: Implications Of the Herpesviral Infections Hypothesis On Prementioning

confidence: 99%

Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment

Qin

2019

Journal of Medical Virology

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Accumulating evidence suggests that infections by herpesviruses might be closely linked to Alzheimer's disease (AD). Pathological hallmarks of AD brains include senile plaques induced by amyloid β peptide (Aβ) in the extracellular space and intracellular neurofibrillary tangles (NFTs) consisting of phosphorylated tau protein. The prevailing hypothesis for the mechanism of AD is amyloid cascade reaction. Recent studies revealed that infections by herpesviruses induce the similar pathological hallmarks of AD, including Aβ production, phosphorylation of tau (P-tau), oxidative stress, neuroinflammation, etc. Aβ peptide is regarded as one of the antimicrobial peptides, which inhibits HSV-1 replication. In the elderly, reactivation of herpesviruses might act as an initiator for amyloid cascade reaction in vulnerable individuals, triggering the neurofibrillary formation of phosphorylated tau and inducing oxidative stress and neuroinflammation, which can further contribute to the accumulation of Aβ and P-tau by impairing mitochondria and autophagosome. Epidemiological studies have shown AD susceptibility genes, such as APOE-ε4 allele, are highly linked to infections by herpesviruses. Interestingly, anti-herpesviral therapy significantly reduced the risk of AD in a large population study. Given that herpesviruses are arguably the most prevalent opportunistic pathogens and often reactivate in the elderly, it is reasonable to argue reactivation of herpesviruses might be major culprits for initiating AD in individuals carrying AD susceptibility genes. In this review, we summarize epidemiological and molecular evidence that support for a hypothesis of herpesviral infections and antimicrobial protection in the development of AD, and discuss the implications for future prevention and treatment of the disease.

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Treatment of epilepsy in patients with Alzheimer’s disease

Cited by 22 publications

References 95 publications

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Incidence and Prevalence of Antiepileptic Medication Use in Community-Dwelling Persons with and without Alzheimer’s Disease

Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment

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