Mesial temporal shape asymmetry as a neuro-imaging correlate of epilepsy in mild cognitive impairment and dementia

Abstract Epilepsy is a common comorbidity of Alzheimer’s disease(AD) and related dementias(ADRD). Both epilepsy and ADRD affect the mesial temporal structures in volume and morphology. Nonetheless, mesial temporal shape and volume asymmetry remain understudied in persons with dementia and mild cognitive impairment, collectively called persons with cognitive impairment (PWCI) and co-morbid epilepsy. We investigated hippocampal and amygdalar left-to-right shape and volume asymmetry in AD (AD_Epi) and non-AD (nonAD_Epi) with co-morbid epilepsy. This multicentre study included participants from 39 US Alzheimer’s disease centres from 9/2005-12/2021. We categorized participants into group 1: PWCI with epilepsy(subclassified into AD_Epi and nonAD_Epi); group 2: PWCI without epilepsy(subclassified into AD_NoEpi and nonAD_NoEpi); and group 3: healthy controls(HC). We used a fixed-ratio, optimal propensity score matching to match group 1 participants to groups 2 and 3. Matching was based on age, sex, and type of dementia (AD vs nonAD) for group 2 and age and sex for group 3. We used FreeSurfer for MRI segmentation of hippocampi and amygdalae. For volume asymmetry, we subtracted the right volume from the left and divided it by the total volume of the structure (right + left). For shape asymmetry, we calculated a 512-point shape model using left and flipped right hippocampi and, similarly, a 256-point shape model for amygdalae. Next, we calculated the point-by-point shape asymmetry between left and right hippocampi and amygdalae in a normal direction for each participant. Multivariable linear models were used to compare volume and shape asymmetry among groups after adjusting for age, sex, total intracranial volume, and dementia severity. We compared AD_Epi vs. AD_NoEpi, nonAD_Epi vs. nonAD_NoEpi, AD_Epi vs. HC, nonAD_Epi vs. HC, AD_NoEpi vs. HC, and nonAD_NoEpi vs. HC. Analyses were adjusted for multiple comparisons. A total of 703 participants were included (391(55.62%) female, average age:70.78 years). These included 35 AD_Epi, 28 nonAD_Epi, 183 AD_NoEpi, 137 nonAD_NoEpi, and 320 HC. For shape analyses, AD_Epi showed greater left-to-right asymmetry (Left smaller than right) in hippocampal tail compared with HC. Those with nonAD_Epi demonstrated greater left–to-right asymmetry in the hippocampal head compared with both nonAD_NoEpi and HC. AD_NoEpi had an asymmetrically smaller left hippocampal head and right amygdala than HC. We found no group differences in volume asymmetries. Our study found left smaller than right hippocampal head asymmetry in non-Alzheimer’s dementia with epilepsy and left smaller than right hippocampal tail asymmetry in Alzheimer’s disease with epilepsy.. These findings suggest that hippocampal shape asymmetry may serve as a neuroimaging correlate of epilepsy in ADRD.