Half a century of research by scientists in the US have demonstrated that individuals who had childhood epilepsy have an increased accumulation of brain amyloid later in life, potentially predisposing them to late-onset disorders like Alzheimer’s.
The accumulation of beta-amyloid protein in the brain is considered an early pathological brain change in Alzheimer’s, although the exact cause of amyloid accumulation is unknown.
The collaborative study by the University of Turku and Åbo Akademi University in Finland and the University of Wisconsin is based on a globally unique population-based cohort, collected by young child neurologist, now Professor Emeritus, Matti Sillanpää, who still leads the cohort.
The cohort has monitored the health and social prognosis of individuals who had childhood epilepsy since the early 1960s and their matched controls since 1992.
The follow-up is conducted progressively at regular intervals in collaboration with domestic and international researchers (TACOE project). The recent study (published in Neurology) examined the brain amyloid accumulation of these individuals, who were on the verge of retirement or already retired, and their controls.
In the previous timepoint of the study (2013-2016), after 50 years of follow-up, researchers observed that those with childhood epilepsy had more amyloid plaques in their brains than the controls.
“The finding was the first of its kind globally, and it was unclear at that point whether the abnormal amyloid accumulation in the brain would continue, further predisposing them to the development of memory disorders. This motivated our current study,” said one of the key figures in the research, Professor of Neurology Juho Joutsa from the University of Turku.
The latest study was conducted seven years after the previous timepoint, with the participants being 60-65-years-old. It included 82% of the previous participants, a total of 36 individuals with childhood-onset epilepsy, and 35 controls. In the patient group, abnormal amyloid accumulation was observed in nearly one-third of the participants, whereas only 11% of the controls showed this accumulation.
During the seven-year follow-up, the patient group accumulated more amyloid in the brain than the controls. The patient group also performed worse in cognitive tests than the controls, but this was not linked to the amount of amyloid plaques.
This suggests that the amyloid accumulation in the brain has not yet led to memory disorders, said Joutsa.
The unique cohort utilised in the study has provided extensive information about childhood epilepsy and its prognosis over decades.
Modern brain imaging methods, which now enabled the study of brain amyloid pathology, were developed decades after the cohort was established.
Joutsa, who was a recently graduated physician at the time, was recruited for brain imaging analyses in the early 2010s.
The study results provide unique new information about the very long-term effects of childhood epilepsy on the brain, and the follow-up continues.
“This study is also an excellent example of what can be achieved scientifically through long-term commitment of both participants and researchers, as well as collaboration across disciplines and generations of researchers,” Joutsa added.
Study details
Progression of amyloid accumulation in late adulthood among people with childhood-onset epilepsy
Juho Joutsa, Juha Rinne, Matti Sillanpää et al.
Published in Neurology on 11 February 2025
Abstract
Background and Objectives
Previous research has demonstrated increased brain amyloid plaque load in individuals with childhood-onset epilepsy in late middle age. However, the trajectory of this process is not yet known. The aim of this study was to determine whether individuals with a history of childhood-onset epilepsy show progressive brain aging in amyloid accumulation in late adulthood (Turku Adult Childhood-Onset Epilepsy study, TACOE).
Methods
Adults from a prospective population-based cohort of individuals with childhood-onset epilepsy, originally recruited 1961–1964, together with matched controls, were scanned with [11C]PIB PET twice: after at least 50 years (TACOE-50) and again after at least 55 years (TACOE-55) from the diagnosis.
Results
At TACOE-55, 31.4% (11/36, mean age 63.3 years, 52.8% female) of individuals from the epilepsy group and 11.4% (4/35, 63.1 year, 54.3%) of controls had a visually abnormal [11C]PIB scan (p = 0.039). At TACOE-55, cortical brain [11C]PIB uptakes were higher and increased more from TACOE-50 in the epilepsy compared with the control group (p < 0.05). In voxelwise whole-brain analyses, the epilepsy group showed significantly higher and more widespread brain amyloid accumulation (pFWE < 0.05).
Discussion
The results demonstrate that childhood-onset epilepsy is associated with an earlier age at onset of amyloidosis and greater progressive amyloid accumulation in late adulthood.
See more from MedicalBrief archives:
Childhood-onset epilepsy may speed brain ageing by 10 years — Finnish study
Alternative treatment for epileptic seizures in children