Midlife epilepsy tied to sixfold risk of dementia before 65, still about 2 in 100

Two in every hundred. That is the share of French adults newly diagnosed with epilepsy between ages 30 and 55 who went on to develop dementia within the next 10 years, before they turned 65. Among people of the same age without epilepsy, it was two in every thousand.

The figures come from a study published on October 14 in Neurology, the journal of the American Academy of Neurology. A team led by Quentin Calonge and Vincent Navarro of Sorbonne University and the Paris Brain Institute combined three nationwide analyses of health records from France and Sweden. People with young-onset dementia were much more likely than matched people without it to have had epilepsy in the years before, and adults diagnosed with epilepsy in midlife had about six times the risk of developing dementia before 65. The study shows an association, not cause, and Navarro is the first to stress the other half of the result. “While these results show a strong relationship between epilepsy and young-onset dementia, it’s important to remember that absolute risk is low,” Navarro said.

What young-onset dementia is, and what was known about epilepsy

Young-onset dementia, also called early-onset dementia, is dementia in which symptoms start before the age of 65. It is uncommon but not rare. A 2021 global review led by Stevie Hendriks estimated that about 119 in every 100,000 adults aged 30 to 64 have it, corresponding to 3.9 million people worldwide.

The link between epilepsy and dementia in older people is well documented. A 2022 meta-analysis of 20 long-term studies found that baseline epilepsy was associated with higher risk of dementia, about double, and that the link ran the other way as well: people with dementia were nearly three times as likely to develop epilepsy. A Welsh study that followed 563,151 residents from their 60th birthday found that people with epilepsy had 2.5 times the rate of dementia, with the strongest link for dementia caused by damage to the brain’s blood vessels. In that study, those first diagnosed at 25 or younger had a dementia rate similar to that of those diagnosed later, which suggests the link is not only about seizures that start late in life. Patients who had ever been prescribed the epilepsy drug sodium valproate also had a higher dementia risk, though that too is an observational comparison. The authors of the 2022 meta-analysis warned that the pooled figures should be carefully interpreted, because the studies behind them varied widely.

What was missing was the younger end. In the authors’ words, epilepsy is linked to late-onset dementia, but evidence for young-onset dementia is limited. A risk factor spotted in midlife would leave more years in which to act on it.

How the French and Swedish epilepsy records were searched

The researchers came at the question from both directions. First they started from the dementia and looked back. Using France’s national health insurance data, they found 11,360 people aged 40 to 64 diagnosed with young-onset dementia between 2016 and 2018 and matched each with 10 people of the same age and sex from the same region who did not have dementia, 113,600 in all. They then checked whether each person had any record of epilepsy, or had been dispensed an antiseizure medicine, in the 10 years before. They repeated the analysis in Swedish national registers covering 1987 to 2016, with 16,433 people with young-onset dementia and 164,330 matched controls.

Then they started from the epilepsy and looked forward. In France, they identified 12,901 adults aged 30 to 55 whose epilepsy was diagnosed in 2008, marked by their first reimbursement for an antiseizure drug. They compared them with 64,083 people who already had epilepsy before 2008 and 129,010 people who did not have it, and followed everyone for up to 10 years, until a dementia diagnosis, death or the end of follow-up. Because some people die before dementia can appear, the analysis treated death as a competing event rather than ignoring it. It also took account of social deprivation and of other illnesses, including stroke, mood disorders and traumatic brain injury.

Both designs have weaknesses that the other partly covers. A look back from dementia can show how common earlier epilepsy is in people who later develop dementia, while following people forward gives an actual risk over time. Neither can show that epilepsy causes dementia.

How strongly epilepsy was linked to dementia before 65

Looking back, the gap was wide. In France, 12.5% of people with young-onset dementia had earlier epilepsy records, against 1.2% of the matched people without dementia. After adjustment, that was nearly four times the odds. Antiseizure medicines were also more common in the years before a dementia diagnosis: 27.3% of those with dementia had received epilepsy medications, against 10.3% of the others, although these drugs have other uses besides epilepsy, and the gap in adjusted odds was smaller, about 44%. The Swedish results were similar to those in France.

Looking forward, the risk was high in relative terms and low in absolute ones. Within the decade, 2.2% of the newly diagnosed people developed young-onset dementia, against 1.74% of those who already had epilepsy and 0.21% of those without it. Once other illnesses and deprivation were accounted for, the newly diagnosed group’s rate was about six times higher compared with individuals without epilepsy. The authors write that the risk was raised in midlife, especially with multimorbidity, that is, in people living with several other long-term illnesses.

The size of that gap invites a closer look at timing, and the team checked it. If epilepsy diagnosed a year or two before dementia were simply an early sign of a brain already in decline, the link should shrink sharply once the first years after an epilepsy diagnosis are set aside. In the French cohort it shrank but did not vanish. The associations attenuated with longer lags but persisted beyond 5 years, meaning the link weakened but remained when the clock started five years after diagnosis.

Which comes first, the seizures or the dementia?

That weakening hints at part of the answer. Seizures and dementia share causes, including strokes, head injuries and other damage to the brain, and some of the overlap in this study may reflect that, even though the analysis adjusted for stroke and brain injury. The arrow can also point backward. A 2017 review in The Lancet Neurology describes how epileptic activity is frequently associated with Alzheimer’s disease, can appear early in the disease and might contribute to it. Those seizures are easy to miss, because they usually present as non-motor seizures, without the jerking movements most people picture, and once Alzheimer’s is under way they can speed up the decline in memory and thinking.

So a seizure disorder diagnosed at 50 could, in some people, be the first visible sign of a disease that will be called dementia at 53. Setting aside five years rules out only the shortest of those gaps, and the review describes seizures appearing at early stages of Alzheimer’s, so the lag result narrows that explanation without excluding it, and the records cannot separate the possibilities. The study also could not say which kinds of epilepsy or dementia were involved. The researchers note that detailed information was not available on the type or cause of dementia cases, or on the type of epilepsy.

Other limits follow from using billing and prescription records. Records like these depend on how doctors code each diagnosis, and the study had no way to check them one by one. Both are high-income countries with universal health care coverage, so the results may not carry over to places where access to neurologists and memory clinics is uneven. The figures given here come mostly from France; the Swedish analysis was a replication of the first design only.

What the epilepsy and dementia results mean for care

For people living with epilepsy, the absolute numbers are the place to start. Even in the newly diagnosed group, about 98 in 100 received no dementia diagnosis over a decade of follow-up. The study does not tell anyone with epilepsy what their own risk is, which depends on age, the cause of their seizures and their other health conditions.

The researchers see the result as an argument for paying attention earlier. “These results support integrating dementia prevention into the care of people with epilepsy,” Navarro said, suggesting that people with epilepsy may benefit from earlier assessments of their cognitive risks and closer management of factors that can be changed, “such as cardiovascular factors like high blood pressure.” The paper itself concludes that the results support “epilepsy inclusion in YOD risk stratification and prevention,” using YOD for young-onset dementia: epilepsy should count as a risk factor when doctors weigh someone’s chance of early dementia. Whether such checks are appropriate for a given person is decided with their doctor.

Across two countries and two designs, epilepsy in midlife went with several times the risk of dementia before 65, a risk that still affected only about 2 in 100 people over 10 years.