Scientists have reported on the association of epilepsy with the risk of dementia before the age of 65

Epilepsy may be associated with an increased risk of dementia before the age of 65. In people with newly diagnosed disease, this risk, after statistical adjustments, turned out to be about six times higher than in people without epilepsy. At the same time, the absolute probability remained low: over ten years, 2.2% of the participants in this group were diagnosed with dementia. What can link the two diseases, how to understand the figures obtained and what conclusions they allow us to draw — in the Izvestia material.

Dementia before the age of 65 is a separate issue

Dementia is usually associated with old age, but it can develop much earlier. The term "early-onset dementia" refers to the onset of symptoms before the age of 65. Here, the word "early" refers to age, not severity: it's not about the initial stage of the disease.

According to the definition of the World Health Organization, dementia affects memory, thinking and the ability to cope with everyday tasks. It can be caused by various diseases and brain damage. Alzheimer's disease is the most common cause, but there are also vascular dementia, Lewy body dementia, and frontotemporal forms.

The manifestations are not limited to forgetfulness. There may be difficulties with choosing words, making decisions, performing familiar tasks, as well as behavioral changes. Therefore, the study of dementia risk is broader than the search for the causes of memory impairment.

The authors of the new study looked specifically at the age of 65, since the association of epilepsy with dementia at a later age has already been studied, while there was less data on early onset. For this task, the scientists combined two approaches: they restored the medical history of people with dementia and separately tracked which diagnoses appeared after the detection of epilepsy.

Two ways to check a single connection

In the first part of the study, the "case—control" principle was used. In French databases, scientists found 11,360 people with dementia diagnosed before the age of 65, and compared them with 113,600 people without such a diagnosis. In Sweden, 16,433 people with dementia and 164,330 participants in the control group were compared.

Ten people of the same age and gender without dementia corresponded to each person with dementia. The researchers then examined medical information from the previous ten years: they searched for records of epilepsy and the prescription of antiepileptic drugs.

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In the French sample, epilepsy was reported in 12.5% of people with dementia and in 1.2% of participants without it. Prescriptions for medications also differed: 27.3% of people with dementia and 10.3% of the control group received medications used for epilepsy. In Sweden, scientists have found a similar pattern.

These indicators describe the medical background of people who were subsequently diagnosed with dementia. They do not mean that 12.5% of all people with epilepsy develop dementia. The second part of the work was needed to assess how often it occurred after the diagnosis of epilepsy.

It included residents of France between the ages of 30 and 55. 12,901 people were first diagnosed with epilepsy in 2008, and 64,083 more were diagnosed earlier. The comparison group consisted of 129,010 people without epilepsy. According to medical data, the researchers followed the participants for a period of up to ten years.

This age range made it possible to study dementia that occurs before the age of 65. At the same time, "newly diagnosed epilepsy" means the date when the disease was detected in the study, and not necessarily the exact moment when its first manifestations appeared.

What has been discovered in ten years

During the follow-up, dementia was detected in 2.2% of participants with newly diagnosed epilepsy. Among people who had epilepsy earlier, the rate was 1.7%, and in the group without epilepsy — 0.2%.

The researchers then took into account other circumstances that could affect the risk of dementia, including stroke, mood disorders, and traumatic brain injuries. After these adjustments, people with newly diagnosed epilepsy had a relative risk about six times higher than those without it. In people with a previous diagnosis, the increase was 74%.

The difference between the two groups with epilepsy alone does not explain why the rates were different. In particular, it cannot be concluded that newly developed epilepsy is necessarily more dangerous than a disease with a long history.: Such a conclusion would require detailed information about the causes, course, and treatment of each case.

Sixfold risk and 2.2%: why both indicators are important

The phrase "six times higher risk" describes the relative difference between the groups. It does not mean that the majority of participants with epilepsy developed dementia, and it does not replace the absolute incidence of the disease.

In terms of one thousand participants, the proportions shown in the work correspond to approximately 22 cases of dementia among people with newly diagnosed epilepsy, 17 among people with a previously diagnosed diagnosis, and two among people without epilepsy. This is a recalculation of the published percentages, not individual research results.

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The difference between the first and third groups was about two percentage points: 2.2% versus 0.2%. This difference is significant for medical observation, but it also shows that approximately 98% of participants with newly diagnosed epilepsy were not diagnosed with dementia during the study period.

Simply dividing 2.2 by 0.2 gives a value of about 11, not six. There is no contradiction here: the proportions describe the actual frequency of diagnoses in the groups, and the sixfold increase is the result of statistical analysis taking into account other factors. These are different indicators that answer different questions.

In addition, ten years of follow-up does not allow us to assess the likelihood of the disease for the rest of our lives. The figures obtained relate to specific groups, age, and study period.

Why doesn't the link explain the reason yet

Epilepsy is a brain disease in which repeated seizures occur due to excessive electrical discharges of nerve cells. Their manifestations vary from brief attention disorders to severe seizures. According to the WHO, severe head injuries, strokes, infections and other brain diseases can be among the causes of epilepsy.

This creates several possible explanations for the discovered connection. For example, the same brain damage can be associated with both seizures and a subsequent deterioration in cognitive function. In this case, an earlier record of epilepsy does not prove that it was she who started the process that led to dementia.

Another possibility that needs to be distinguished when interpreting such data is that the brain disease is already developing, but has not yet been recognized as dementia. The sequence of diagnoses in the medical database does not always coincide with the sequence of biological changes. For a new job, this is a possible explanation, not an established mechanism.

Earlier studies also show that the relationship between these conditions can be two-way. Based on data from the Framingham Study, published in Neurology in 2020, each of the two conditions was associated with about twice the risk of developing the other later compared to the control groups. These results were obtained in a different sample and do not replace new estimates for middle-aged people, but show the complexity of the relationship itself.

Accounting for stroke or injury in a statistical model helps to reduce the impact of concomitant factors. However, it does not turn the observation of medical records into evidence of causality. In addition, the new work did not provide detailed information about the types and causes of dementia, as well as about the types of epilepsy.

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Not every memory disorder means dementia.

Epilepsy may cause difficulties with attention and memory, but their causes require a separate assessment. According to the US National Institute of Neurological Disorders and Stroke, some antiepileptic drugs can cause side effects affecting concentration and memory.

Therefore, complaining about forgetfulness by itself does not establish either dementia or its cause. In clinical evaluation, the severity of changes, their development over time, and the impact on a person's independence are important.

The new work does not allow attributing the increased risk to medications. The researchers did take into account information about their appointment, but more frequent use of drugs among people with dementia does not prove that the treatment caused the disease. For such a conclusion, it would be necessary to separately study specific drugs, indications, dosages, duration of therapy and the condition of patients.

The issue of changing treatment is also not solved on the basis of a single statistical relationship. In the NICE guidelines on epilepsy, drug withdrawal is considered as an individual decision with an assessment of the risk of seizures returning. The dementia study itself does not provide grounds for self-termination of therapy.