Alzheimer Disease and Seizures: Focal Epilepsy, Lateralized Pathology in AD Related

A spatial association exists between the epileptogenic focus and tau deposition, amyloid deposition, and neurodegeneration in early Alzheimer disease (AD), according to study results published in Neurology.

Researchers conducted a cross-sectional study to assess spatial relationships between the epileptogenic zone and tau and amyloid deposition, as well as brain atrophy in people with early clinical stages of AD who developed late-onset, otherwise unexplained focal epilepsy. Adults aged 60 to 85 with mild cognitive impairment or dementia and a diagnosis of epilepsy with seizures initiating after age 55 and otherwise unexplained etiology were eligible for inclusion in the AD with epilepsy group. The AD control group without epilepsy comprised adults aged 46 to 100 who were stably medicated for at least 30 days with a clinical diagnosis of mild cognitive impairment or AD and a Clinical Dementia Rating (CDR) score of at least 0.5. Positron emission tomography (PET) imaging, structural magnetic resonance imaging (MRI), and overnight ambulatory scalp electroencephalogram (EEG) were performed. Tau and amyloid deposition and trends in brain atrophy were compared between groups.

The groups with and without epilepsy comprised 8 (mean age at PET, 66.5; mean age at first clinical seizure, 67.9; women, 62.5%) and 14 (mean age at PET, 71.7; women, 35.7%) individuals, respectively.

Among the 8 patients with AD with epilepsy, 5 had left temporal lobe epilepsy and 3 had right temporal lobe epilepsy. Four patients had only nonconvulsive seizures, 2 patients had only convulsive seizures, and 2 patients had both nonconvulsive and convulsive seizures.

All patients with seizure had an asymmetric tau deposition pattern with more tau deposited in the epileptogenic hemisphere. Higher tau deposition was observed in the lateral temporal (r, 0.94; P =.023), lateral parietal (r, 0.91; P =.023), frontal (r, 0.88; P =.023), and medial parietal (r, 0.88; P =.023) regions of the epileptogenic hemisphere.

Patterns of amyloid vs tau asymmetry were more subtle and variable. Most patients exhibited areas of asymmetrically greater amyloid within the epileptogenic hemisphere, with greater deposition in the lateral temporal (r, 0.94; P =.011), lateral parietal (r, 0.94; P =.011), and occipital (r, 0.80; P =.023) regions. Two patients with AD-related epilepsy exhibited amyloid deposition in the contralateral hemisphere.

Increased atrophy was observed within the epileptogenic hemisphere. According to cortical thickness, atrophy was concentrated in the lateral temporal (r, 0.94; P =.008), lateral parietal (r, 0.94; P =.008), and frontal (r, 0.94; P =.008) regions. According to subcortical volume, atrophy was concentrated in the nucleus accumbens (r, 0.94; P =.023), amygdala (r, 0.85; P =.023), and hippocampus (r, 0.85; P =.023).

Compared with patients without epilepsy, patients with epilepsy had greater asymmetrical patterns in tau, amyloid, and atrophy in the epileptogenic hemisphere, but no significant patterns in non-epileptogenic regions.

Study limitations include the cross-sectional design, small sample size, and reduced generalizability of results to a more diverse population sample.

“Our results reveal a spatial association between the epileptogenic focus and tau deposition, amyloid deposition, and neurodegeneration in early clinical stages of AD,” the study authors concluded.