Abstracts

Rationale: Cognitive impairment is a common comorbidity of temporal lobe epilepsy(TLE), but its mechanism is still unclear. Neuropathological and neuroimaging studies have revealed that neurodegeneration might play a significant role in it, but the pattern of neurodegeneration and its correlation with cognitive function still need further study. We aimed to precisely localize and quantify the hyperphosphorylated tau (pTau) and amyloid-β (Aβ) burden in the whole brain of TLE patients by PET molecular imaging, and to investigate the correlation between the pTau and Aβ load and cognitive function.


Methods: Our study included 20 patients with temporal lobe epilepsy (12 with cognitive impairment and 8 without) and 11 matched healthy volunteers, who underwent neuropsychological tests, ¹⁸F-fluorodeoxyglucose PET (brain glucose metabolism PET), ¹⁸F-MK6240 PET (tau-PET) and ¹¹C-Pittsburgh compound B PET (Aβ-PET). Data processing of PET data was performed using PMOD software, and standardised uptake ratios (SUVR) were calculated using the cerebellar cortex as the reference area. We mirror-flipped the SUVR results, with the left side defined as ipsilateral to the epileptogenic focus and the right side as contralateral. Correlations between SUVR in each brain region of three PET modalities and neuropsychological testing and clinical factors were assessed separately.


Results: Patients with temporal lobe epilepsy had reduced glucose metabolism predominantly in the temporal lobe and hippocampus ipsilateral to the epileptic focus compared to healthy controls. Compared with healthy controls, MK6240 SUVR was significantly higher in TLE patients with cognitive deficits including but not limited to hippocampus, heschl, superior temporal gyrus, middle temporal gyrus, fusiform gyrus, cingulate gyrus, and so on (p<0.01). Verbal fluency test scores and MoCA scores were negatively correlated with MK6240 SUVR in most brain regions (p<0.05). Compared with healthy controls, the PIB SUVR in the TLE patients tended to decrease. It could be seen that digit dymbol dubstitution test scores were negatively correlated with PIB SUVR in the left hippocampus (r=-0.393, p=0.035), the left lingual (r=-0.445, p=0.016), the right fusiform (r=-0.417, p=0.024) and the right middle temporal gyrus (r=-0.439, p=0.017). A positive correlation with focal impaired awareness seizure frequency in individual brain regions was observed for both MK6240 SUVR and PIB SUVR.


Conclusions: We detected high loads of pTau in TLE patients with concomitant cognitive deficits, and loads of pTau correlated with cognitive function. But Aβ loading showed the opposite trend, which is distinct from classical neurodegenerative disorders, especially from Alzheimer's disease. Our findings suggest that neurodegeneration plays a role in cognitive dysfunction in TLE through pTau.


Funding: National Multidisciplinary Cooperative Diagnosis and Treatment Capacity Project for Major Diseases of Xiangya Hospital, Central South University (z027001), Natural Science Foundation of Hunan Province,China（2024JJ2096）