Presumed aetiologies and clinical outcomes of non-lesional late-onset epilepsy.

BACKGROUND AND PURPOSE: Our objective was to define phenotypes of non-lesional late-onset epilepsy (NLLOE) depending on its presumed aetiology and to determine their seizure and cognitive outcomes at 12 months. METHODS: In all, 146 newly diagnosed NLLOE patients, >50 years old, were prospectively included and categorized by four presumed aetiological subtypes: neurodegenerative subtype (patients with a diagnosis of neurodegenerative disease) (n = 31), microvascular subtype (patients with three or more cardiovascular risk factors and two or more vascular lesions on MRI) (n = 39), inflammatory subtype (patient meeting international criteria for encephalitis) (n = 9) and unlabelled subtype (all individuals who did not meet the criteria for other subtypes) (n = 67). Cognitive outcome was determined by comparing for each patient the proportion of preserved/altered scores between initial and second neuropsychological assessment. RESULTS: The neurodegenerative subtype had the most severe cognitive profile at diagnosis with cognitive complaint dating back several years. The microvascular subtype was mainly evaluated through the neurovascular emergency pathway. Their seizures were characterized by transient phasic disorders. Inflammatory subtype patients were the youngest. They presented an acute epilepsy onset with high rate of focal status epilepticus. The unlabelled subtype presented fewer comorbidities with fewer lesions on brain imaging. The neurodegenerative subtype had the worst seizure and cognitive outcomes. In other groups, seizure control was good under antiseizure medication (94.7% seizure-free) and cognitive performance was stabilized or even improved. CONCLUSION: This new characterization of NLLOE phenotypes raises questions regarding the current International League Against Epilepsy aetiological classification which does not individualize neurodegenerative and microvascular aetiology per se.

Exploring the everyday impacts and memory intervention needs of people with transient epileptic amnesia: A qualitative study.

People with transient epileptic amnesia (TEA) experience deficits in memory, however, little is known about their everyday experience of this, and no memory intervention studies have been conducted within this group. Using a two-part qualitative method, this study explored the lived experience of people with TEA and possible avenues for memory intervention. Fourteen people with TEA participated in either a focus group (n = 7) or an online survey (n = 7) to answer questions regarding their memory difficulties, impact on their lives, and strategies to mitigate these problems. Perceived barriers and facilitators to participating in a group memory intervention program were discussed. Thematic content analysis identified key themes regarding impacts on the individual and their relationships. Although some positive outcomes regarding family support and personal acceptance were described, most participants described negative impacts on relationships and mood. A range of strategies to mitigate memory problems were reported, although some people did not use any. Participants identified practical and socio-emotional advantages to memory intervention, with perceived barriers around individual applicability, preferences, and ability to engage. While individual preferences need to be considered, a group-based memory intervention may help address cognitive and mental health concerns, particularly for those newly diagnosed with TEA.

Functional imaging in late-onset epilepsy: A focused review.

INTRODUCTION: About 25 % of new-onset epilepsies are diagnosed after age 65. Late-onset epilepsy (LOE) is predicted to become a major healthcare problem in the next 15 years as the global population increases and ages. Neurodegenerative disorders account for 10-20 % of LOE, while over 20 % of these patients have an unknown etiology. Established diagnostic tools such as FDG-PET and novel biomarkers of neurodegeneration including amyloid and tau PET hold a lot of promise in diagnosing and ruling out neurodegenerative disorders in these patients. METHODS: We conducted a literature search to identify articles involving LOE populations and using one or more functional neuroimaging techniques. RESULTS: A total of 5 studies were identified through Boolean searching and snowballing. These were highly heterogenous with respect to operational definitions of LOE, analyses and interpretation pipelines. CONCLUSION: While there is some evidence for feasibility and usefulness of FDG- and Amyloid PET in LOE, methodological heterogeneities in the available literature preclude any notable conclusions. Future research in this field will benefit from a consensus on epilepsy-specific analysis and interpretation guidelines for amyloid and tau PET.

Alzheimer's Disease and Epilepsy: Exploring Shared Pathways and Promising Biomarkers for Future Treatments.

Background: Alzheimer's disease (AD) and epilepsy represent two complex neurological disorders with distinct clinical manifestations, yet recent research has highlighted their intricate interplay. This review examines the association between AD and epilepsy, with particular emphasis on late-onset epilepsy of unknown etiology, increasingly acknowledged as a prodrome of AD. It delves into epidemiology, pathogenic mechanisms, clinical features, diagnostic characteristics, treatment strategies, and emerging biomarkers to provide a comprehensive understanding of this relationship. Methods: A comprehensive literature search was conducted, identifying 128 relevant articles published between 2018 and 2024. Results: Findings underscore a bidirectional relationship between AD and epilepsy, indicating shared pathogenic pathways that extend beyond traditional amyloid-beta and Tau protein pathology. These pathways encompass neuroinflammation, synaptic dysfunction, structural and network alterations, as well as molecular mechanisms. Notably, epileptic activity in AD patients may exacerbate cognitive decline, necessitating prompt detection and treatment. Novel biomarkers, such as subclinical epileptiform activity detected via advanced electroencephalographic techniques, offer promise for early diagnosis and targeted interventions. Furthermore, emerging therapeutic approaches targeting shared pathogenic mechanisms hold potential for disease modification in both AD and epilepsy. Conclusions: This review highlights the importance of understanding the relationship between AD and epilepsy, providing insights into future research directions. Clinical data and diagnostic methods are also reviewed, enabling clinicians to implement more effective treatment strategies.

Late onset epilepsy and stroke: Diagnosis, pathogenesis and prevention.

The association of stroke and late-onset epilepsy (LOE) is discussed with special regard to its diagnosis, pathogenesis, and prevention. In addition to epidemiological data, including those from different age groups, the mechanisms for the development of acute symptomatic and remote symptomatic seizures are reviewed. The risk factors associated with seizures and post-stroke epilepsy (PSE) are considered, along with the methodological limitations of the study. For future research, the distinction between acute and remote symptomatic seizure before or after seven days from stroke onset should be reviewed because different acute symptomatic seizures (ASSs) themselves can entail a variable PSE risk. The definition of LOE by age is hitherto inconsistent. Comparing adult lifespan epochs, it is evident that stroke and seizures exhibit similar prevalence profiles. Young adulthood, old adulthood, and elderly epochs may be relevant for the differentiation of LOE subtype by age, vascular comorbidity, and other characteristics. A step-scheme strategy as a possible contribution to cerebrovascular prevention approaches is proposed.

Cardiovascular risk factor assessment in late-onset seizures: A study protocol to assess the value of structured intervention.

OBJECTIVE: A growing body of evidence suggests patients with late-onset seizures are at an increased risk of stroke, but the potential for reducing cardiovascular morbidity through risk factor screening and management is unknown. We aim to determine whether individuals with new-onset unprovoked seizures after middle age should undergo vascular risk assessment. The long follow-up needed to assess stroke risk and the known benefit of vascular risk factor modification make a standard RCT logistically and ethically challenging. Instead, we propose and have developed a protocol for a cluster project assessing the effect of vascular risk factor screening in an intervention trial as well as a cohort study. METHODS: Participating neurology clinics will implement standard cardiovascular risk factor assessment into the routine evaluation for individuals aged ≥50 years attending their first specialized consultation after an unprovoked seizure, excluding those with progressive brain disease. The project has two interlinked components: a prospective single group trial, in which risk factor assessment is performed and subsequent management is followed for one year; and a register-based cohort study examining the long-term effects of the intervention on a system level by comparing patients attending initial consultations in the 2 years after start of the study, with patients seen in the four preceding years at the same clinics. ANALYSIS: The primary outcome of the intervention trial is the proportion of patients receiving subsequent pharmacological treatment. The primary outcome of the cohort study is the incidence of acute stroke in the Swedish Stroke Register. ETHICS AND DISSEMINATION: Swedish Ethical Review Authority approval (which is valid for 2 years only) will be sought when funding is obtained. The results will be disseminated through peer-reviewed scientific publications. REGISTRATION DETAILS: The study will be registered at clinicaltrials.gov. PLAIN LANGUAGE SUMMARY: A first seizure in a middle-aged or older person indicates a higher risk of stroke. It is not known whether investigating and treating blood pressure, blood cholesterol, or similar risk factors after a first seizure is an effective way to prevent stroke. A traditional clinical study would need too many patients and it would be unethical not to treat the control group. We have designed a study in which participating neurology departments change their practice to test and treat vascular risk factors. Patients are then compared to historic controls using registered data.

Brain tumor-associated epilepsies in adulthood: Current state of diagnostic and individual treatment options.

Brain tumors are one of the most frequent causes of structural epilepsy and set a major burden on treatment costs and the social integrity of patients. Although promising oncological treatment strategies are already available, epileptological treatment is often intractable and requires lifelong epileptological care. Therefore, treatment strategies must be adapted to age-related needs, and specific aspects of late-onset epilepsy (LOE) must be considered. The practical implementation of individual decisions from tumor boards and the current state of the art in scientific knowledge about pathological mechanisms, modern diagnostic procedures and biomarkers, and patient-individualized treatment options into practical epileptological disease management is a prerequisite. This narrative review focuses on the current work progress regarding pathogenesis, diagnosis, and therapy. Exemplarily, interdisciplinary approaches for optimized individualized therapy will be discussed, emphasizing the combination of neurological-epileptological and oncological perspectives.

Fluid biomarkers unveil signatures of pathological aging.

Aging is a multifaceted and highly varied process in the brain. Identifying aging biomarkers is one means of distinguishing pathological from physiological aging. The aim of this narrative review is to focus on two new developments in the field of fluid biomarkers and draw attention to this excellent tool for the early detection of potential brain pathologies that delay, alter, or enable physiological aging to become pathological. Pathological aging can lower the threshold for the development of specific diseases such as late-onset epilepsy. Fluid biomarkers can reveal pathological levels at an early stage and thus indicate disease processes in the brain that begin before symptoms develop; they thus differ from physiological aging.

Bidirectional relationship between late-onset epilepsy (LOE) and dementia: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: To explore the bidirectional relationship of late-onset epilepsy (LOE) with dementia and Alzheimer's disease (AD). METHODS: Using the common electronic databases, including PubMed, Cochrane Library databases and EMBASE, we systematically reviewed published cohort studies that assessed the risk of LOE in individuals comorbid with dementia or AD, and those with dementia or AD comorbid with LOE that had been published up to 31 March 2023. The data extraction process was carried out independently by two authors. The summary adjusted relative ratio (aRR) was calculated by employing Rev Man 5.3 for the inclusion of studies. To investigate the origins of heterogeneity, we conducted both subgroup and sensitivity analyses. In the presence of heterogeneity, a random-effects model was employed. To evaluate potential publication bias, we utilized the funnel plot and conducted Begg's and Egger's tests. RESULTS: We included 20 eligible studies in the final analysis after a rigorous screening process. Pooled results indicated that LOE was association with an increased risk of all-cause dementia (aRR: 1.34, 95% confidence interval [CI]: 1.13-1.59) and AD (aRR: 2.49, 95% CI: 1.16-5.32). In addition, the pooled effect size for LOE associated with baseline AD and all-cause dementia were 3.51 (95% CI: 3.47-3.56) and 2.53 (95% CI: 2.39-2.67), respectively. Both sensitivity and subgroup analyses showed that these positive correlations persisted. According to the results of the Egger's and Begg's tests, as well as visual inspection of funnel plots, none of the studies appeared to be biased by publication. CONCLUSION: The findings suggested that LOE is a potential risk factor for dementia and AD, and vice versa, dementia and AD are both potential risk indicators for LOE. Since there is substantial heterogeneity among the cohorts analyzed and more cohort studies should be conducted to confirm the correlations found in the current study.

Multi-class Modeling Identifies Shared Genetic Risk for Late-onset Epilepsy and Alzheimer's Disease.

Background: Previous studies have established a strong link between late-onset epilepsy (LOE) and Alzheimer's disease (AD). However, their shared genetic risk beyond the APOE gene remains unclear. Our study sought to examine the shared genetic factors of AD and LOE, interpret the biological pathways involved, and evaluate how AD onset may be mediated by LOE and shared genetic risks. Methods: We defined phenotypes using phecodes mapped from diagnosis codes, with patients' records aged 60-90. A two-step Least Absolute Shrinkage and Selection Operator (LASSO) workflow was used to identify shared genetic variants based on prior AD GWAS integrated with functional genomic data. We calculated an AD-LOE shared risk score and used it as a proxy in a causal mediation analysis. We used electronic health records from an academic health center (UCLA Health) for discovery analyses and validated our findings in a multi-institutional EHR database (All of Us). Results: The two-step LASSO method identified 34 shared genetic loci between AD and LOE, including the APOE region. These loci were mapped to 65 genes, which showed enrichment in molecular functions and pathways such as tau protein binding and lipoprotein metabolism. Individuals with high predicted shared risk scores have a higher risk of developing AD, LOE, or both in their later life compared to those with low-risk scores. LOE partially mediates the effect of AD-LOE shared genetic risk on AD (15% proportion mediated on average). Validation results from All of Us were consistent with findings from the UCLA sample. Conclusions: We employed a machine learning approach to identify shared genetic risks of AD and LOE. In addition to providing substantial evidence for the significant contribution of the APOE-TOMM40-APOC1 gene cluster to shared risk, we uncovered novel genes that may contribute. Our study is one of the first to utilize All of Us genetic data to investigate AD, and provides valuable insights into the potential common and disease-specific mechanisms underlying AD and LOE, which could have profound implications for the future of disease prevention and the development of targeted treatment strategies to combat the co-occurrence of these two diseases.

Clinical, imaging, and biomarker evidence of amyloid- and tau-related neurodegeneration in late-onset epilepsy of unknown etiology.

Accumulating evidence suggests amyloid and tau-related neurodegeneration may play a role in development of late-onset epilepsy of unknown etiology (LOEU). In this article, we review recent evidence that epilepsy may be an initial manifestation of an amyloidopathy or tauopathy that precedes development of Alzheimer's disease (AD). Patients with LOEU demonstrate an increased risk of cognitive decline, and patients with AD have increased prevalence of preceding epilepsy. Moreover, investigations of LOEU that use CSF biomarkers and imaging techniques have identified preclinical neurodegeneration with evidence of amyloid and tau deposition. Overall, findings to date suggest a relationship between acquired, non-lesional late-onset epilepsy and amyloid and tau-related neurodegeneration, which supports that preclinical or prodromal AD is a distinct etiology of late-onset epilepsy. We propose criteria for assessing elevated risk of developing dementia in patients with late-onset epilepsy utilizing clinical features, available imaging techniques, and biomarker measurements. Further research is needed to validate these criteria and assess optimal treatment strategies for patients with probable epileptic preclinical AD and epileptic prodromal AD.

Sleep apnea, hypoxia, and late-onset epilepsy: the Atherosclerosis Risk in Communities study.

STUDY OBJECTIVE: Sleep apnea is associated with unexplained epilepsy in older adults in small studies. We sought to determine the relationship between sleep apnea and additional sleep characteristics and late-onset epilepsy, adjusting for comorbidities, using data from the large, prospective Atherosclerosis Risk in Communities (ARIC) Study cohort. METHODS: We used Medicare claims to identify cases of late-onset epilepsy (LOE) in ARIC participants. We used polysomnography data from 1309 ARIC participants who also participated in the Sleep Heart Health Study in 1995-1998, and demographic and comorbidity data from ARIC. Later risk of LOE was evaluated using survival analysis with a competing risk of death. We also used survival analysis in 2672 ARIC participants to identify the association between self-reported obstructive sleep apnea (2011-2013), and the risk of subsequent LOE. RESULTS: Late-midlife oxygen desaturation to less than 80% during sleep was associated with subsequent development of LOE, adjusted subhazard ratio 3.28 (1.18-9.08), but the apnea-hypopnea index was not related. Participant report of diagnosis of sleep apnea in 2011-2013 was also associated with subsequent LOE, adjusted subhazard ratio 2.59 (1.24-5.39). CONCLUSIONS: Sleep apnea and oxygen saturation nadir during sleep are associated with LOE, independently of hypertension and other comorbidities. These potentially modifiable risk factors could have large clinical implications for LOE.

Association of comorbid-socioeconomic clusters with mortality in late onset epilepsy derived through unsupervised machine learning.

BACKGROUND AND OBJECTIVES: Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality. METHODS: We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster. RESULTS: From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters. SIGNIFICANCE: Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.

New-onset Geriatric Epilepsy in a Latin American Country: A Multi-centric Study from Mexico.

Background: In Latin America, epilepsy in the elderly is a neglected issue that has never been studied. The epidemiological transition has significantly altered the demographics of epilepsy, and therefore, we would like to draw attention to this topic. Objective: We require local real-world evidence, as the literature often depicts a different scenario, including pharmacological management. Methods: From 2007 to 2018, we recruited all patients with new-onset geriatric epilepsy (first seizure after the age of 60) tracked from ten Mexican hospitals, adding them to patients with similar characteristics from a previously published study. The diagnosis was confirmed in all patients by a certified neurologist, and they were also studied using a conventional electroencephalogram and imaging workup. Results: A diagnosis of new-onset geriatric epilepsy (Elderly patients was established in 100 cases. No specific cause was found in 26% of patients, while 42% had a stroke and 10% had neurocysticercosis (NCC). Monotherapy was the choice in 83 patients, and phenytoin was the most used drug (50%), followed by carbamazepine (25%). Conclusion: NCC remains a frequent cause of new-onset geriatric epilepsy. This distribution is not seen in the literature, mainly representing patients from wealthy economies. In our setting, financial constraints influence the choice of the drug, and newer antiepileptic drugs should be made more affordable to this population with economic and physical frailty.

New-onset Geriatric Epilepsy in a Latin American Country: A Multi-centric Study from Mexico

ABSTRACT Background: In Latin America, epilepsy in the elderly is a neglected issue that has never been studied. The epidemiological transition has significantly altered the demographics of epilepsy, and therefore, we would like to draw attention to this topic. Objective: We require local real-world evidence, as the literature often depicts a different scenario, including pharmacological management. Methods: From 2007 to 2018, we recruited all patients with new-onset geriatric epilepsy (first seizure after the age of 60) tracked from ten Mexican hospitals, adding them to patients with similar characteristics from a previously published study. The diagnosis was confirmed in all patients by a certified neurologist, and they were also studied using a conventional electroencephalogram and imaging workup. Results: A diagnosis of new-onset geriatric epilepsy (Elderly patients was established in 100 cases. No specific cause was found in 26% of patients, while 42% had a stroke and 10% had neurocysticercosis (NCC). Monotherapy was the choice in 83 patients, and phenytoin was the most used drug (50%), followed by carbamazepine (25%). Conclusion: NCC remains a frequent cause of new-onset geriatric epilepsy. This distribution is not seen in the literature, mainly representing patients from wealthy economies. In our setting, financial constraints influence the choice of the drug, and newer antiepileptic drugs should be made more affordable to this population with economic and physical frailty.

Epileptic Prodromal Alzheimer's Disease Treated with Antiseizure Medications: Medium-Term Outcome of Seizures and Cognition.

BACKGROUND: The medium term outcome (over more than one year) of epileptic prodromal AD (epAD) patients treated with antiseizure medications (ASMs) is unknown in terms of seizure response, treatment tolerability, and cognitive and functional progression. OBJECTIVE: To describe such medium term outcome over a mean of 5.1±2.1 years. METHODS: We retrospectively compared 19 epAD patients with 16 non-epileptic prodromal AD (nepAD) patients: 1) at baseline for demographics, medical history, cognitive fluctuations (CFs), psychotropic medications, MMSE scores, visually rated hippocampal atrophy, CSF neurodegenerative biomarkers, and standard EEG recordings; 2) during follow-up (FU) for psychotropic medications, MMSE progression, and conversion to dementia. In the epAD group, we analyzed baseline and FU types of seizures as well as each line of ASM with the corresponding efficacy and tolerability. RESULTS: At baseline, the epAD group had more CFs than the nepAD group (58% versus 20%, p = 0.03); focal impaired awareness seizures were the most common type (n = 12, 63.1%), occurring at a monthly to quarterly frequency (89.5%), and were well controlled with monotherapy in 89.5% of cases (including 63.1% seizure-free individuals). During FU, treated epAD patients did not differ significantly from nepAD patients in MMSE progression or in conversion to dementia. CONCLUSION: Epilepsy is commonly controlled with ASMs over the medium term in epAD patients, with similar functional and cognitive outcomes to nepAD patients. Pathophysiologically, epilepsy is likely to be an ASM-modifiable cognitive aggravating factor at this stage of AD.

Transient epileptic amnesia: a retrospective cohort study of 127 cases, including CSF amyloid and tau features.

BACKGROUND: Transient epileptic amnesia (TEA) is a late-onset epilepsy syndrome encompassing transient iterative amnesias and interictal cognitive impairment, two features that overlap with incipient neurodegenerative dementias. We, therefore, examined the yield of CSF amyloid and tau biomarkers in TEA. METHODS: In this retrospective study, 127 TEA patients with unremarkable imaging findings were divided into 2 groups, namely, CSF (n = 71) and no-CSF (n = 56). Both were compared for demographics; medical history; baseline neurological, cognitive, and behavioral features; baseline mesial temporal lobe atrophy; and cognitive follow-up at a median of 13 months. CSF samples were examined for amyloid ß-42 peptide as well as phospho-tau and total-tau levels. RESULTS: At baseline, the CSF-TEA group had significantly (p < 0.01) more frequent mild parkinsonism (42.9% vs. 20%) and cognitive concerns (31% vs. 10.7%), a more blunted sense of smell (34.3% vs. 9.4%), a lower baseline MMSE score (27 vs. 28.9), a more frequent amnestic mild cognitive impairment profile (69% vs. 42.6%), and more atrophic hippocampal changes. At follow-up, the CSF-TEA group had significantly (p < 0.01) lower MMSE scores (27.8 vs. 28.9). CSF analyses revealed amyloid and/or tau changes in 27 patients (38%), including an Alzheimer's disease (AD) profile in 17 (24%). CONCLUSIONS: This study shows a good diagnostic value of CSF sampling in a specific population of TEA with characteristics suggestive of incipient degenerative diseases (i.e., red flags). It argues for TEA being the inaugurating feature in some cases of AD. More broadly, our results suggest an etiological heterogeneity in TEA.

Overlapping and distinct phenotypic profiles in Alzheimer's disease and late onset epilepsy: a biologically-based approach.

Due to shared hippocampal dysfunction, patients with Alzheimer's dementia and late-onset epilepsy (LOE) report memory decline. Multiple studies have described the epidemiological, pathological, neurophysiological, and behavioral overlap between Alzheimer's Disease and LOE, implying a bi-directional relationship. We describe the neurobiological decline occurring at different spatial in AD and LOE patients, which may explain why their phenotypes overlap and differ. We provide suggestions for clinical recognition of dual presentation and novel approaches for behavioral testing that reflect an "inside-out," or biologically-based approach to testing memory. New memory and language assessments could detect-and treat-memory impairment in AD and LOE at an earlier, actionable stage.

Meta-analysis of the risk of dementia in elderly patients with late-onset epilepsy.

Although available literature indicates a high risk of dementia in elderly patients with late-onset epilepsy (LOE), the findings are yet inconsistent and relevant risk factors are unclear, rendering rational clinical interpretation rather challenging. This article systematically evaluates the risk of dementia in elderly LOE patients. The potential risk factors were analyzed to provide a specific basis for clinical prediction of dementia. PubMed and web of science databases were searched for the published cohort studies of dementia in elderly LOE patients. The search results were subject to a meta-analysis with Stata16.0 statistical software. Seven articles were included for a comparison of dementia risk between epilepsy cases and controls, yielding a hazard ration (HR) of 2.1 (95 %CI：1.6～2.75，p = 0.00); dementia was more prevalent in female patients than in male counterparts, though without a statistical difference [1.2 % (95 %CI, 0.9 %-1.6 %) vs. 0.8 % (95 %CI, 0.5 %-1.1 %)]; compared with the non-LOE group, the LOE population reported a significantly higher incidence of diabetes mellitus [14.1 % (95 %CI, 12.8 %-15.4 %) vs. 10.9 % (95 %CI, 10.1 %-11 %), p < 0.01]. The findings suggest that elderly patients with late-onset epilepsy run a higher risk of dementia than non-epileptic patients and diabetes mellitus may serve as a potential risk factor for dementia in this elderly populace.

Late-onset seizures and epilepsy: Electroclinical features suggestive of autoimmune etiology.

Introduction: Late-onset epilepsy (LOE) has recently become a topic of intense research. Besides stroke, tumors, and dementia, autoimmune encephalitis (AE) has emerged as another possible cause of recurrent seizures in the elderly, and may account for a proportion of cases of LOE of unknown origin (LOEUO). This 24-h ambulatory electroencephalography (AEEG)-based study compared patients with LOEUO and AE to identify features suggestive of immune-mediated seizures in the elderly. Materials and methods: We retrospectively reviewed 232 AEEG examinations performed in patients over 55 years with ≥6-month follow-up, and selected 21 subjects with AE and 25 subjects with LOEUO. Clinical charts and AEEG recordings were carefully analyzed. Results: Twenty-five patients with LOEUO (12 women, mean age at onset 67.9 years) and 21 AE subjects (8 women, mean age at onset 65.7 years) were enrolled. High-frequency seizures were reported in 20/21 AE and 7/25 LOEUO cases (p < 0.00001). Focal aware seizures were more common in AE (14/21 vs. 6/25, p = 0.00058), whereas "isolated" focal-to-bilateral tonic-clonic seizures occurred in 5/25 patients with LOEUO only (p = 0.053). AE subjects reported ictal autonomic manifestations more frequently (p = 0.0033). Three-hundred-seventy and 24 seizures were recorded in 13/21 patients with AE and 3/25 patients with LOEUO, respectively (p = 0.0006). Interictal epileptiform discharges were observed in 70% of both groups, but their sleep activation was more common in AE (p = 0.06). Conclusion: Our study shows that high-frequency focal seizures with autonomic manifestations should raise the suspicion of AE in the elderly with new-onset seizures. It also highlights the relevant contribution of AEEG, which might reduce the diagnostic delay and provide useful clues to recognize AE.