Authors :
Presenting Author: Alice Ballerini, PhD – University of Modena and Reggio Emilia
Niccolò Biagioli, MD – University of Modena and Reggio Emilia
Chiara Carbone, PhD – University of Modena and Reggio Emilia
Annalisa Chiari, MD – Neurology Unit, AOU Modena
Manuela Tondelli, MD, PhD – University of Modena and Reggio Emilia
Giulia Vinceti, MD – Neurology Unit, AOU Modena
Roberta Bedin, PhD – University of Modena and Reggio Emilia
Marcella Malagoli, MD – Neuroradiology Unit, AOU Modena
Maurilio Genovese, MD – Neuroradiology Unit, AOU Modena
Simona Scolastico, MD – University of Modena and Reggio Emilia
Giada Giovannini, PhD – AOU Modena Academic Hospital
Matteo Pugnaghi, MD, PhD – Neurophysiology Unit and Epilepsy Centre, AOU Modena
Niccolò Orlandi, MD – University of Modena and Reggio Emilia
Louis Lemieux, PhD – UCL Institute of Neurology, London
stefano meletti, MD, PhD – University of Modena and Reggio Emilia, Italy
Giovanna Zamboni, MD, PhD – University of Modena and Reggio Emilia
Anna Elisabetta Vaudano, MD, PhD – University of Modena and Reggio Emilia
Rationale: The incidence of epilepsy can be well described by a U-shape curve, with its highest prevalence of new-onset cases occurring during childhood and in individuals aged 50 years and older
1,2. Considering the growing age of the world population, the incidence of late-onset epilepsies (LOEs) is expected to increase significantly
3. The majority of LOEs result from structural causes (i.e., cerebrovascular disease
4,5, traumatic brain injuries
6,7, and brain tumors
8,9). However, up to 20% of LOEs lack identifiable structural damage and/or defined etiology; these cases are termed late-onset epilepsy of unknown etiology (LOEU)
10. Previous studies have proposed the temporal forms of LOEU (i.e., late-onset TLE; LO-TLE) as possible neurodegenerative diseases with a greater propensity to develop AD
11–13. Herein, we aimed to characterize the pattern of cortical atrophy and cerebrospinal fluid (CSF) biomarkers of AD (total and phosphorylated tau, and β-amyloid) in a selected population of LO-TLE of unknown origin.
Methods: We prospectively enrolled individuals with temporal lobe epilepsy onset after the age of 50, no cognitive impairment, and no history of ischemic and/or hemorrhagic events. The patients underwent a structural MRI scan and CSF biomarkers measurement. Imaging and biomarkers data were compared to three retrospectively collected groups: (
i) age-sex-matched healthy controls, (
ii) patients with Mild Cognitive Impairment (MCI) and abnormal CSF AD biomarkers (MCI-AD), and (
iii) patients with MCI and normal CSF AD biomarkers (MCI-noAD).
Results: From a pool of 52 patients, twenty consecutive eligible LO-TLE patients with a mean disease duration of 1.8 years were recruited. As control populations, 25 patients with MCI-AD, 25 patients with MCI-noAD, and 25 healthy controls were enrolled. CSF biomarkers returned normal values in LO-TLE, significantly different from patients with MCI due to AD (
Table 1 and
Fig. 1A). There were no differences in cortico-subcortical atrophy between epilepsy patients and healthy controls, while patients with MCI demonstrated widespread injuries of cortico-subcortical structures (
Fig. 1B).
Conclusions: We aimed to contribute to the literature on LO-TLE of unknown origin by providing insights from both CSF biomarkers and neuroimaging. Individuals with a late-onset form of temporal lobe epilepsy, characterized by short disease duration and normal CSF β-amyloid and tau protein levels, showed patterns of cortical thickness and subcortical volumes not significantly different from healthy controls, but highly different from patients with MCI, either due to Alzheimer’s Disease or not. Taken together, our results suggest that LO-TLE itself may not intrinsically represent a risk factor for developing AD.
Funding:
- A. Ballerini had postdoc funding from the Ministry of University and Research (PRIN project 2022, Prot. 2022BNE97C; PI: S. Meletti).
- The enrollment of MCI patients was supported by the grant “Dipartimenti di Eccellenza 2018-2022” to the Department of Biomedical, Metabolic, and Neural Sciences, University of Modena.
- C. Carbone, A. Chiari, M. Tondelli, M. Malagoli, and G. Zamboni are funded by the European Union ERC (UnaWireD, project number 101042625).