Alzheimer’s disease (AD) is widely recognized as a progressive neurodegenerative disorder, with symptoms primarily revolving around memory loss and a decline in cognitive functions. While the disease is most often associated with dementia, a significant complication is the presence of seizures. This established link between AD and seizure activity is important for both patients and caregivers to understand, as it affects diagnosis, prognosis, and treatment strategies. Seizures represent a physical manifestation of the underlying electrical instability in the brain caused by the disease.
How Often Seizures Occur in Alzheimer’s
Patients with Alzheimer’s disease face a significantly higher risk of developing seizures compared to the general elderly population. While the lifetime prevalence of seizures in AD can vary widely between studies, it is consistently elevated, with some reports suggesting the risk is up to ten times greater than in age-matched individuals without the disease. The risk of seizures appears to increase as the disease progresses to more advanced stages of dementia.
A particularly strong association exists in patients with early-onset Alzheimer’s disease (EOAD), defined as symptom onset before age 65. Individuals in this group have a substantially higher likelihood of experiencing unprovoked seizures, sometimes reported as high as 11% to 45%. For those with onset between 50 and 59 years old, the risk of a first unprovoked seizure may be up to 87 times higher compared to the age-matched general population. This considerable increase in risk makes seizures a genuine concern in the management of the disease.
The Neurological Connection Between Alzheimer’s and Epilepsy
The underlying cause of seizure activity in Alzheimer’s disease is rooted in the same pathological processes that drive cognitive decline. The hallmark proteins of AD, Amyloid-beta (A\(\beta\)) plaques and hyperphosphorylated Tau tangles, are directly implicated in increasing the electrical excitability of neurons. Toxic, soluble forms of Amyloid-beta are thought to disrupt the delicate balance between excitatory and inhibitory signals in the brain, leading to neuronal hyperexcitability.
Specifically, these pathological changes interfere with key neurotransmitter systems, primarily the glutamatergic (excitatory) and GABAergic (inhibitory) pathways. A\(\beta\) and Tau aggregates impair the function of GABAergic interneurons, which are essential for controlling and dampening neuronal activity, effectively reducing the brain’s natural braking system. At the same time, the glutamatergic system, which uses the excitatory neurotransmitter glutamate, can become overactive.
This imbalance, where excitation significantly outweighs inhibition, creates a state of network hyperexcitability, particularly in regions like the hippocampus. The resulting electrical overactivity is not only the basis for seizure generation but may also accelerate the cognitive decline characteristic of AD. The presence of epileptiform activity can create a vicious cycle, as increased neuronal activity, in turn, promotes the production and deposition of Amyloid-beta and Tau proteins.
Types of Seizures Seen in Alzheimer’s Patients
Seizures in Alzheimer’s patients often present subtly, making them difficult to distinguish from typical symptoms of dementia or delirium. Instead of the dramatic full-body convulsions often associated with epilepsy, these patients frequently experience focal seizures. These focal seizures start in a specific area of one hemisphere of the brain and may or may not spread to become a generalized seizure.
A common presentation is the focal impaired awareness seizure, previously known as a complex partial seizure. These events can manifest as a period of confusion, a blank stare, or repetitive, automatic behaviors like lip-smacking or fumbling with clothes, often lasting less than three minutes. Because these symptoms involve cognitive fluctuation and reduced awareness, they can easily be misinterpreted as a temporary worsening of the patient’s existing cognitive impairment.
Another significant type is non-convulsive status epilepticus (NCSE), which represents continuous or rapidly recurring seizure activity without major motor symptoms. NCSE is a medical emergency that can present as a sudden, profound, and sustained change in a person’s behavior, awareness, or confusion, lasting for an extended period. Myoclonic seizures, characterized by brief, shock-like jerks of a muscle or group of muscles, are also reported, particularly in advanced stages of the disease.
Confirming Diagnosis and Treatment Approaches
The subtle nature of seizures in AD patients necessitates specialized diagnostic tools to confirm the activity. The primary method for diagnosis is the Electroencephalogram (EEG), which records the electrical activity of the brain. When subtle or non-convulsive seizures are suspected, prolonged video-EEG monitoring is often employed, allowing clinicians to correlate any behavioral changes with simultaneous electrical recordings.
Diagnosis is challenging because the manifestation can be so mild that it is missed entirely, or the symptoms are simply attributed to the progression of dementia. Identifying subclinical epileptiform activity, which is electrical seizure-like activity on an EEG without outward clinical symptoms, is also important as it is associated with a more rapid cognitive decline.
Treatment for confirmed seizures typically involves anti-epileptic drugs (AEDs), but careful selection is paramount due to the cognitive vulnerability of AD patients. Many standard AEDs can exacerbate memory problems, sedation, or confusion in the elderly. Newer-generation AEDs such as levetiracetam and lamotrigine are generally preferred, as they are often better tolerated and have a lower risk of worsening cognitive function.
Studies suggest that levetiracetam, often used at a low dose, can be particularly effective and may even improve learning and memory in AD patients who have epileptic activity. The goal of treatment is not only to control seizures but also to prevent further cognitive decline that may be driven by the abnormal electrical discharges. The choice of medication must be highly individualized, prioritizing agents that offer seizure control with minimal adverse effects on the patient’s already compromised cognition.