Introduction: In past years, a possible bidirectional link between epilepsy and Alzheimer's disease (AD) has been proposed: if AD patients are more likely to develop epilepsy, people with late-onset epilepsy evidence an increased risk of dementia. Furthermore, current research suggested that subclinical epileptiform discharges may be more frequent in patients with AD and network hyperexcitability may hasten cognitive impairment.
Areas Covered: In this narrative review, the authors discuss the recent evidence linking AD and epilepsy as well as seizures semeiology and epileptiform activity observed in patients with AD. Finally, anti-seizure medications (ASMs) and therapeutic trials to tackle seizures and network hyperexcitability in this clinical scenario have been summarized.
Expert Opinion: There is growing experimental evidence demonstrating a strong connection between seizures, neuronal hyperexcitability, and AD. Epilepsy in AD has shown a good response to ASMs both at the late and prodromal stages. The new generation ASMs with fewer cognitive adverse effects seem to be a preferable option. Data on the possible effects of network hyperexcitability and ASMs on AD progression are still inconclusive. Further clinical trials are mandatory to identify clear guidelines about treatment of subclinical epileptiform discharges in patients with AD without seizures.
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http://dx.doi.org/10.1080/14737175.2023.2278487 | DOI Listing |
The hippocampus forms memories of our experiences by registering processed sensory information in coactive populations of excitatory principal cells or ensembles. Fast-spiking parvalbumin-expressing inhibitory neurons (PV INs) in the dentate gyrus (DG)-CA3/CA2 circuit contribute to memory encoding by exerting precise temporal control of excitatory principal cell activity through mossy fiber-dependent feed-forward inhibition. PV INs respond to input-specific information by coordinating changes in their intrinsic excitability, input-output synaptic-connectivity, synaptic-physiology and synaptic-plasticity, referred to here as experience-dependent PV IN plasticity, to influence hippocampal functions.
View Article and Find Full Text PDFCurr Neuropharmacol
January 2025
Departments of Neurology & Neurosurgery, and Physiology, Montreal Neurological Institute-Hospital, McGill University, 3801 University Street, Montréal, Québec, H3A 2B4, Canada.
Background: Catamenial epilepsy, which is defined as a periodicity of seizure exacerbation occurring during the menstrual cycle, has been reported in up to 70% of epileptic women. These seizures are often non-responsive to medication and our understanding of the relation between menstrual cycle and seizure generation (i.e.
View Article and Find Full Text PDFJ Neuroinflammation
January 2025
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98104, USA.
Traumatic brain injury is a leading cause of chronic neurologic disability and a risk factor for development of neurodegenerative disease. However, little is known regarding the pathophysiology of human traumatic brain injury, especially in the window after acute injury and the later life development of progressive neurodegenerative disease. Given the proposed mechanisms of toxic protein production and neuroinflammation as possible initiators or contributors to progressive pathology, we examined phosphorylated tau accumulation, microgliosis and astrogliosis using immunostaining in the orbitofrontal cortex, a region often vulnerable across traumatic brain injury exposures, in an age and sex-matched cohort of community traumatic brain injury including both mild and severe cases in midlife.
View Article and Find Full Text PDFNPJ Parkinsons Dis
January 2025
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20852, USA.
ΑBSTRACT: In Parkinson's disease (PD), Lewy pathology deposits in the cerebral cortex, but how the pathology disrupts cortical circuit integrity and function remains poorly understood. To begin to address this question, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. We reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern.
View Article and Find Full Text PDFElectroencephalographic (EEG) recordings in individuals with Fragile X Syndrome (FXS) and the mouse model of FXS ( KO) display cortical hyperexcitability at rest, as well as deficits in sensory-driven cortical network synchrony. A form of circuit hyperexcitability is observed in cortical slices of KO mice as prolonged persistent activity, or Up, states. It is unknown if the circuit mechanisms that cause prolonged Up states contribute to FXS-relevant EEG phenotypes.
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