Alzheimer’s disease (AD) is a progressive disorder causing memory loss and cognitive decline. Seizures are a significant and often under-recognized complication in individuals living with AD. Compared to the general population, people with Alzheimer’s disease face a substantially increased risk of developing seizures, sometimes up to ten times greater. This connection arises from the profound structural and chemical changes occurring in the Alzheimer’s brain.
Neuropathological Mechanisms Linking Alzheimer’s and Seizures
The fundamental cause of seizures in AD is the development of neuronal hyperexcitability, which is an excessive and uncontrolled firing of brain cells. This hyperexcitability is directly driven by the hallmark protein pathologies of Alzheimer’s disease.
The accumulation of Beta-Amyloid (Aβ) protein outside the neurons is one primary factor leading to this electrical instability. Soluble forms of the Aβ protein, before they aggregate into plaques, interfere with normal communication pathways between brain cells, increasing neuronal excitability.
A second pathology involves the Tau protein, which forms neurofibrillary tangles inside the neurons. When Tau becomes hyperphosphorylated and forms tangles, it destabilizes the neuron, contributing to dysfunction and cell death.
The combined effect of these protein pathologies leads to a critical imbalance between the brain’s excitatory and inhibitory signals. There is evidence of selective loss or dysfunction of inhibitory GABAergic neurons, which use the neurotransmitter GABA to quiet down other cells. Losing these “brakes” results in a lowered seizure threshold, making the brain highly susceptible to abnormal electrical discharges.
Identifying Specific Risk Factors and Clinical Triggers
While the underlying AD pathology creates biological susceptibility, specific clinical factors and external events often trigger a seizure. The risk increases significantly as the disease progresses and cognitive impairment becomes more severe.
Patients with early-onset Alzheimer’s disease (EOAD), particularly those with genetic mutations like in the PSEN1 gene, have a higher lifetime risk of seizures than those with the late-onset form. Co-morbidities common in the elderly, such as a history of stroke or cerebrovascular events, also increase the likelihood of seizures. These conditions add structural damage to an already compromised brain network.
Many medications used to manage AD symptoms or behavioral issues can inadvertently lower the seizure threshold. For example, certain antipsychotic medications (clozapine and quetiapine) or antidepressants (trazodone) are known to increase seizure risk. Even the rapid withdrawal of certain AD treatments, such as acetylcholinesterase inhibitors, may contribute to a lowered seizure threshold.
Acute systemic changes can transiently trigger a seizure in a susceptible AD brain. Triggers such as severe dehydration, a high fever from an infection, or profound sleep deprivation place additional stress on the unstable neural environment. These acute factors can push the hyperexcitable brain past its threshold, resulting in a clinical seizure event.
Types of Seizures Observed in Alzheimer’s Patients
Seizures in Alzheimer’s patients often present in subtle or atypical ways that can be challenging to recognize, frequently mimicking other symptoms of dementia. The most common type observed is a focal seizure, which originates in a localized area of one hemisphere of the brain. These events may manifest as brief periods of staring, repetitive non-purposeful movements (like lip-smacking or picking at clothes), or transient confusion.
Because focal seizures are often non-convulsive, they can easily be misattributed to behavioral disturbances or fluctuations in dementia severity. Generalized seizures, such as tonic-clonic seizures involving full-body convulsions, affect both sides of the brain but are less frequent than focal types. The subtlety of focal seizures means the true rate of seizure activity in AD patients is likely underestimated.
One specific, often-missed manifestation is Non-Convulsive Status Epilepticus (NCSE), where a patient experiences prolonged or continuous seizure activity without typical motor convulsions. In an AD patient, NCSE may appear as a sustained, unexplained period of altered consciousness, severe confusion, or a sudden decline in cognitive function. Recognizing this condition is particularly important because it is a medical emergency requiring prompt diagnosis, typically through an electroencephalogram (EEG), and treatment.