Abstracts

Rationale: Epilepsy is a common co-morbidity of Alzheimer’s disease (AD) and related dementias. However, the neuro-imaging biomarkers of epilepsy in AD and non-AD dementias have not been extensively studied. The hippocampus is one of the most frequently affected structures in the brain in both dementia and epilepsy. Nonetheless, hippocampal shape and volumetrics remain understudied in people with dementia and co-morbid epilepsy. Our study aimed to investigate the hippocampal shape asymmetry on MRI brain as a neuro-imaging biomarker in people with AD (AD+epi) and non-AD dementias (non-AD+epi) with co-morbid epilepsy.


Methods: This cross-sectional multicenter study is based on data of participants recruited from 39 Alzheimer’s disease centers in the US between September 2005 and December 2021. We categorized participants into 3 groups: Group 1: people with dementia and co-morbid epilepsy (further subclassified into AD+epi and non-AD+epi); Group 2: people with dementia without epilepsy (further subclassified into AD-epi and non-AD-epi); and Group 3: healthy controls (HC). All participants with dementia and co-morbid epilepsy who had an MRI scan available were included. We utilized a fixed-ratio, optimal propensity score matching to select people with dementia without epilepsy and HC. Propensity score matching was based on age, sex, and type of dementia (AD vs non-AD) for group 2 and age and sex for group 3.



To investigate hippocampal morphology, we calculated a 512-point shape model using both left hippocampi and flipped right hippocampi along the sagittal plane. Next, we calculated the asymmetry between left and right hippocampi along the normal direction at each of these 512 points for each participant. Finally, multivariable linear models were used to compare asymmetry among groups after adjusting for age, sex, and total intracranial volume. All points with statistical significance on the mean hippocampal surface were utilized to elucidate localized, morphological differences between groups.


Results: A total of 703 participants were included for analysis (391 (55.62%) female, average age :70.78 years). These included 35 AD+Epi, 28 non-AD+Epi, 183 AD-Epi, 137 non-AD-Epi, and 320 HC. We compared AD+Epi vs. AD-Epi, Non-AD+Epi vs. non-AD-Epi, AD+Epi vs. HC, and non-AD+Epi vs. HC. After adjusting for covariates of age, sex, and total intracranial volumes, the non-AD group with epilepsy compared to the non-AD without epilepsy had significantly higher asymmetric left hippocampal head atrophy compared to the right hippocampal head. Similarly, non-AD group with epilepsy compared to HC had an even more profound asymmetric left hippocampal head atrophy compared to right hippocampal head (Figure 1 shows purple points with statistically significant difference between the 2 sides). AD+Epi had no differences in hippocampal shape asymmetry compared to AD-Epi and HC.


Conclusions: Our study found that the presence of a more profound left hippocampal head asymmetric atrophy compared to the right hippocampal head may be observed in non-AD dementia and co-morbid epilepsy. These findings suggest that hippocampal morphology may serve as a biomarker for epilepsy in non-AD dementia.

Funding: Alzheimer's Association, NIH