Risk factors for dementia development, frailty, and mortality in older adults with epilepsy – A population-based analysis

Subota, Ann; Josephson, Colin B.; McMillan, Jacqueline; Keezer, Mark R; González-Izquierdo, Arturo; Holroyd‐Leduc, Jayna

doi:10.1016/j.yebeh.2021.108006

Cited by 22 publications

(17 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Late-onset epilepsy is defined 5 when the onset occurs after age 55 years [18,20,75]. The risk, nevertheless, continues to increase even after this age, with a reported incidence of untriggered seizures of 80.8 cases/100.000 inhabitants/year at age 60 compared to 135-175 cases/100.000 inhabitants/year at age 80 [76][77][78].…”

Section: Late Onset Epilepsymentioning

confidence: 99%

“…Indeed, multiple studies support a higher prevalence of mild cognitive impairment (MCI) in late-onset epilepsy (40-55%) [75,85] and in temporal lobe epilepsies (TLE) in which prevalence is up 60% [84]. The amount of temporomedial IEDs and hippocampal onset seizures correlate with progressive episodic memory decline in TLE [20,78,86]. In turn, up to 50% of LOEU patients have frequent multidomain, dysexecutive-predominant MCI with frequent involvement of visuospatial functions [9,87].…”

Section: Late Onset Epilepsymentioning

confidence: 99%

See 1 more Smart Citation

Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications

Altuna¹,

Olmedo²,

Carmona‐Iragui³

et al. 2022

Preprint

View full text Add to dashboard Cite

Epilepsy and Alzheimer's disease (AD) incidence increase with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age and abnormal AD biomarkers in PET and or CSF are frequently found in late onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes including neuronal hyperexcitability and an early excitatory-inhibitory dysregulation leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both β-amyloid and tau protein aggregates, the anatomopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epileptiform activity and electroclinical seizures in AD appears to accelerate progression of cognitive decline and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASM). There is also a potential role for ASMs to be used as disease-modifying drugs in AD.

show abstract

Section: Late Onset Epilepsymentioning

confidence: 99%

Section: Late Onset Epilepsymentioning

confidence: 99%

Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications

Altuna¹,

Olmedo²,

Carmona‐Iragui³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, 3904 articles were excluded by reviewing title or abstract and full-text. After screening, 16 articles [6][7][8][9][10][11][12][13][15][16][17]21,22,24,33,38 were included in the meta-analysis. Four additional studies 14,18,20,23 were included by manual search.…”

Section: Study Selectionmentioning

confidence: 99%

“…[6][7][8][9][10][11][12][13] The bi-directional association between dementia and seizures has been supported by emerging evidence. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Individuals with seizures tend to be more vulnerable to developing dementia. This association can be attributed to multiple factors.…”

mentioning

confidence: 99%

“…In addition to age and genetic factors, several environmental risk factors and other diseases, including epilepsy or seizures, also play an important role in determining the onset of non-hereditary dementia. [6][7][8][9][10][11][12][13] The bi-directional association between dementia and seizures has been supported by emerging evidence. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Individuals with seizures tend to be more vulnerable to developing dementia.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Bidirectional influences between seizures and dementia: A systematic review and meta‐analysis

Zhao

Chen

Zhang

et al. 2022

Int J Geriat Psychiatry

View full text Add to dashboard Cite

Objectives Dementia and seizures often co‐exist, but the association between these two disorders is not well established. Therefore, this systematic review and meta‐analysis aimed to clarify the relationship between seizures and dementia. Methods The PubMed, EMBASE, CBM, and CNKI databases were used to search for relevant publications from inception to August 25, 2021. Data extraction was performed by two authors independently. The random‐effects model was adopted to evaluate the pooled estimates. Results Two nested case‐control studies and 18 cohort studies were included in the meta‐analysis. Seizures were associated with the development of dementia and Alzheimer's disease (AD), and the pooled relative risk (RR) was 2.51 [95% confidence intervals (CI) = 1.87–3.36, p < 0.001] and 1.61 (95% CI = 1.42–1.82, p < 0.001), respectively. Pooled RR estimating the effect of dementia on seizures risk was 3.68 (95% CI = 3.05–4.44, p < 0.001). In addition, the pooled effect size of dementia on epilepsy risk was 3.02 (95% CI = 2.16–4.23, p < 0.001). The subgroup analyses suggested that vascular risk factors could confound the associations between these two disorders. Seizures might independently and significantly increase the risk of dementia, and in turn, dementia might predispose an individual to a higher risk of seizures. Conclusions These results suggested that dementia and seizures share common pathogenesis and might be treated with similar preventive treatment measures. Vascular changes in patients with dementia or seizures should also be examined.

show abstract

Does Alzheimer's disease with mesial temporal lobe epilepsy represent a distinct disease subtype?

Zawar

2023

Alzheimer's & Dementia

View full text Add to dashboard Cite

Alzheimer's disease (AD) patients have a high risk of developing mesial temporal lobe epilepsy (MTLE) and subclinical epileptiform activity. MTLE in AD worsens outcomes. Therefore, we need to understand the overlap between these disease processes. We hypothesize that AD with MTLE represents a distinct subtype of AD, with the interplay between tau and epileptiform activity at its core. We discuss shared pathological features including histopathology, an initial mesial temporal lobe (MTL) hyperexcitability followed by MTL dysfunction and involvement of same networks in memory (AD) and seizures (MTLE). We provide evidence that tau accumulation linearly increases neuronal hyperexcitability, neuronal hyper‐excitability increases tau secretion, tau can provoke seizures, and tau reduction protects against seizures. We speculate that AD genetic mutations increase tau, which causes proportionate neuronal loss and/or hyperexcitability, leading to seizures. We discuss that tau burden in MTLE predicts cognitive deficits among (1) AD and (2) MTLE without AD. Finally, we explore the possibility that anti‐seizure medications improve cognition by reducing neuronal hyper‐excitability, which reduces seizures and tau accumulation and spread. Highlights We hypothesize that patients with Alzheimer's disease (AD) and mesial temporal lobe epilepsy (MTLE) represents a distinct subtype of AD. AD and MTLE share histopathological features and involve overlapping neuronal and cortical networks. Hyper‐phosphorylated tau (pTau) increases neuronal excitability and provoke seizures, neuronal excitability increases pTau, and pTau reduction reduces neuronal excitability and protects against seizures. The pTau burden in MTL predicts cognitive deficits among (1) AD and (2) MTLE without AD. We speculate that anti‐seizure medications improve cognition by reducing neuronal excitability, which reduces seizures and pTau.

show abstract

Risk factors for dementia development, frailty, and mortality in older adults with epilepsy – A population-based analysis

Cited by 22 publications

References 61 publications

Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications

Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications

Bidirectional influences between seizures and dementia: A systematic review and meta‐analysis

Does Alzheimer's disease with mesial temporal lobe epilepsy represent a distinct disease subtype?

Contact Info

Product

Resources

About