Abstracts

Rationale: To determine the course of brain and cognitive aging in a population-based cohort of participants with uncomplicated childhood-onset epilepsy (COE) and controls, followed over five decades, with focus on a recent five-year (2012-2017) prospective in-person assessment of clinical, cognitive and neuroimaging status.

Methods: The cohort consisted of 51 aging participants with COE and their 52 matched controls who underwent detailed in-person prospective neurologic, neuropsychological and neuroimaging (structure, diffusion, amyloid deposition) assessments in 2012 followed by reassessment in 2017 to characterize interval change and the relation of identified changes to clinical epilepsy status (remitted vs. active epilepsy) and health and lifestyle factors. Retention over the 5-year interval was 80% for COE and 88% for controls (41 COE and 40 control participants). Participants were examined neurologically, cognitively (language, memory, executive function, speed), MRI was evaluated clinically and via Freesurfer vertex analyses, and brain amyloid uptake was assessed by PET 11C-Pittsburgh compound B [PIB] ligand evaluated visually by a consensus of two experienced clinical investigators.

Results: At follow-up the mean age of the COE participants was 63.2 years (SD 4.14, range 55.8–70.6) and 63.0 years (SD 4.13, range 56.0–69.9) for controls. Neurologic signs were significantly more common in COE participants not in remission (p=0.015) with cerebellar signs the most frequent abnormality (p < 0.001). Neurologic signs in general (p=0.008) and cerebellar signs in particular (p=0.018) were significantly more common in focal than in generalized epilepsies. Peripheral neuropathy occurred particularly in subjects with active epilepsy with higher lifetime phenytoin load. MRI white matter abnormalities were significantly associated with absence of vocational education (p=0.011), and MRI hippocampal atrophy in COE subjects associated with arterial hypertension (p=0.017). In the combined study cohort of COE subjects and controls, presenting neurologic signs increased both in the subjects and controls from the 2012 to 2017 study. Regarding five-year interval cognitive course using a common threshold of meaningful cognitive change (z < - 1.5) corrected for demographics and practice, the COE group showed significant (p < 0.05) prospective declines versus controls on measures of verbal reasoning, immediate recall and set-shifting. COE participants with active epilepsy showed additional significant (p < 0.05) adverse declines compared to controls and COE participants with remitted epilepsy in delayed memory and object naming. Regarding amyloid imaging, in 2012 22% of COE participants and 7% of controls were PIB positive (p=0.03). In 2017, 33% of the COE compared to 11% of controls were PIB positive (p=0.04).

Conclusions: Clinical, cognitive and neuroimaging findings show brain aging trajectories that are more accelerated in COE participants with active adult childhood-onset epilepsy, and particularly in focal epilepsy. in terms of brain amyloid accumulation, subjects with childhood epilepsy appear approximately 10 years advanced in brain aging compared to matched controls.

Funding: Please list any funding that was received in support of this abstract.: CURE Epilepsy, Finnish Government Research Grant, and Pro Humanitate Foundation.