Cognition and dementia in elderly patients with epilepsy

Abstract and Introduction

Abstract

With advances in the field of health care and the aging of the population, the number of older adults with epilepsy is expected to increase dramatically in the world whole. In developed countries, the highest incidence of epilepsy is already affecting people over 65 years of age and, as life expectancy increases, people who have developed the disease have been diagnosed with epilepsy. epilepsy at a young age also live longer. Recent findings show that older people with epilepsy are more likely to suffer from cognitive impairment and that there could be a significant two-way relationship between epilepsy and dementia. Thus, some people with epilepsy may be at higher risk of developing dementia, while people with certain forms of dementia, especially Alzheimer's disease and vascular dementia, present significantly greater risk. high to develop epilepsy. Consistent with this emerging view, epidemiological findings reveal that people with epilepsy and people with Alzheimer's disease share common risk factors. Recent studies in Alzheimer's disease and late-onset epilepsy also suggest common pathological connections mediated by underlying vascular changes and / or tau pathology. Meanwhile, electrophysiological and neuroimaging investigations in epilepsy, Alzheimer's disease and vascular dementia have focused interest on dysfunction of the network level, which could be important in mediation cognitive dysfunction in these three conditions. In this review, we examine whether seizures promote dementia, whether dementia causes seizures, or whether common underlying pathophysiological mechanisms cause both. We examine evidence that cognitive impairment is associated with epilepsy in the elderly (over 65 years) and the prognosis of patients with developing epilepsy, with an emphasis on the mechanisms common factors that may explain the cognitive deficits observed in epilepsy and Alzheimer's disease. Our analyzes suggest that there is a considerable crossover between epilepsy, Alzheimer's disease and cerebrovascular disease, which raises the possibility that a better understanding of shared mechanisms under these conditions can help improve not only seizures but also epileptogenesis and cognitive dysfunction

About 65 million people worldwide suffer from epilepsy, of which about 80% live in developing regions (Birbeck, 2010; Ngugi et al., 2010). In the United Kingdom> 600 000 people, nearly 1 in 100 (Joint Epilepsy Council, 2011) and the United States> 3 million people or 0.84 out of 100 (Helmers and others 2015) . Several studies have consistently shown that the peak incidence is higher in the elderly, from age 65 (Annegers and others 1999, Hussain and others 2006). In fact, about 25% of new epilepsies are diagnosed after this age (Joint Epilepsy Council, 2011). Given that the global population over 65 years of age will increase by about 400 million to reach nearly one billion by 2030, the number of older adults with epilepsy should increase considerably.

The population of older adults with epilepsy (defined here> 65 years) includes two main groups: those who have suffered from epilepsy for many years and who, thanks to the improvement of health care, now live older and those who develop epilepsy de novo later. While several underlying causes may contribute to the onset of epilepsy in the elderly (Stefan, 2011), cerebrovascular disease accounts for 50 to 70% of cases and is the most common cause (Brodie and 2009; Choi and others 2017). Recent work in the United States has shown that the risk of epilepsy is highest in people with cerebrovascular disease aged 75 to 79 years, with African Americans being particularly exposed (Choi et al. , 2017). The incidence of epilepsy was highest in elderly patients with stroke. Others have shown that the first year after a stroke, the risk of developing epilepsy can be multiplied by 20 (Brodie et al. 2009). The exact pathophysiology of stroke-related epilepsy is not established, but intracerebral hemorrhage, hemorrhagic transformation of ischemic stroke, the severity of l? Stroke, cortical involvement and venous vein thrombosis increase the risk of seizures (Conrad 2013; Zhang and others 2014).

Elderly people who have suffered head trauma are also 2.5 times more likely to develop post-traumatic epilepsy than their younger counterparts and up to 20% of epilepsy older people may be attributed to head trauma (Annegers and others 1998, Bruns and Hauser, 2003). Dementia and neurodegenerative disorders account for 10 to 20% of late-onset epilepsy cases (Stefan, 2011), with most of the research currently focused on Alzheimer's disease. Patients with Alzheimer's disease aged 65 years and older are at risk up to 10 times higher for epilepsy (Hommet et al. 2008, Pandis and Scarmeas , 2012). Other causes of dementia have received much less attention, but a large study in the United Kingdom reported that in people over 65, people with vascular dementia had a similar likelihood of developing seizures or of epilepsy (Imfeld and 2013).

Importantly, some findings also suggest that elderly patients with epilepsy have a higher risk of developing cognitive impairment and ultimately dementia (van Duijn et al., 1991; and others 1995). Why should this be the case? In this review, we examine whether convulsions favor dementia, whether dementia causes convulsions, or whether common underlying pathophysiological mechanisms are responsible for both. First, we consider the evidence regarding cognitive function and the higher potential risk of dementia in elderly patients (aged over 65 years) with epilepsy. We then move on to the results that suggest that there could be a two-way link between epilepsy and dementia, so that patients with dementia also appear to be at greater risk of developing seizures (Subota and others 2017). We discuss evidence of common lifestyle and vascular risk factors in epilepsy and dementia, then consider potential shared molecular linkages, including new evidence of tau pathology in elderly patients with dementia. epilepsy (Sen and 2007 Thom and others 2011, Tai and others 2016). Finally, we examine emerging evidence that suggests that extensive changes in the cerebral network in Alzheimer's disease (with our concomitant vascular pathology) and epilepsy may contribute to cognitive dysfunction under these conditions (Wandschneider et al., 2014; and others 2016, Palop and Mucke, 2016, Chong and others 2017), including the remote effects of interictal epileptiform discharges (IEDs). (Kleen et al 2013, Gelinas and others 2016, Ung and others 2017).

Our examination of these disparate results leads us to the conclusion that the data do not allow us to draw any definitive mechanistic conclusions, they show that it is an area of ​​interest. important investigation that can be applied to both patients with epilepsy and dementia. It is now well established that many patients diagnosed clinically with Alzheimer's disease present a mixed pathology with concomitant cerebrovascular changes at autopsy, and vice versa (Rahimi and Kovacs, 2014) . Thus, lifestyle targeting and vascular risk factors could offer important therapeutic opportunities to modify the pathological processes underlying these pathologies as well as the progression of cognitive decline in epileptic persons