Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment

Abstract

Epilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer’s disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects were obtained from the Alzheimer’s Disease Neuroimaging Initiative database. Whole brain and region of interest analyses were conducted between patient groups and controls, as well as between temporal lobe epilepsy patients with early-onset (age of onset <50 years) and late-onset (>50 years) seizures. Older adults with temporal lobe epilepsy demonstrated a similar pattern and magnitude of medial temporal lobe atrophy to amnestic mild cognitive impairment. Region of interest analyses revealed pronounced medial temporal lobe thinning in both patient groups in bilateral entorhinal, temporal pole, and fusiform regions (all P < 0.05). Patients with temporal lobe epilepsy demonstrated thinner left entorhinal cortex compared to amnestic mild cognitive impairment (P = 0.02). Patients with late-onset temporal lobe epilepsy had a more consistent pattern of cortical thinning than patients with early-onset epilepsy, demonstrating decreased cortical thickness extending into the bilateral fusiform (both P < 0.01). Both temporal lobe epilepsy and amnestic mild cognitive impairment groups showed significant memory and language impairment relative to healthy control subjects. However, despite similar performances in language and memory encoding, patients with amnestic mild cognitive impairment demonstrated poorer delayed memory performances relative to both early and late-onset temporal lobe epilepsy. Medial temporal lobe atrophy and cognitive impairment overlap between older adults with temporal lobe epilepsy and amnestic mild cognitive impairment highlights the risks of growing old with epilepsy. Concerns regarding accelerated ageing and Alzheimer’s disease co-morbidity in older adults with temporal lobe epilepsy suggests an urgent need for translational research aimed at identifying common mechanisms and/or targeting symptoms shared across a broad neurological disease spectrum.

Characterization of Hippocampal-Thalamic-Cortical Morphometric Reorganization in Temporal Lobe Epilepsy

“…Thalamic volume in R-TLE seemed to be less affected by seizure burden. Cortical thickness changes have been used to study the extratemporal cortical involvement in TLE in several previous studies, and the frontal, parietal, and occipital regions were all shown to be affected (25,26,46). Significant thinning was present over the bilateral precentral, paracentral, and frontal opercular gyri, as well as ipsilateral medial orbital cortex (26).…”

“…We found both R-TLE and L-TLE had a common pattern of cortical volume loss, which was in the ipsilateral precentral and the inferior frontal gyri. Precentral gyrus atrophy has been observed in TLE ( 26 , 46 ), which was a characteristic used to differentiate cases of amnestic cognitive impairment from TLE ( 46 ). Primary motor cortex is located in the precentral gyrus, and was reported to reorganize in L-TLE, resulting in handedness shifting ( 48 ).…”

Sleep: The Tip of the Iceberg in the Bidirectional Link Between Alzheimer's Disease and Epilepsy

“…Finally, retrospective or prospective population-based studies or projects using datasets from large memory clinics or databases cannot verify the diagnostic method for all patients in the cohort ( 122 , 123 , 127 , 128 , 131 , 132 , 211 ). Using only imagery and neuropsychological data for diagnosis might inflate the percentage of “AD” patients with epilepsy, given that patterns of cortical atrophy and cognitive symptoms can be highly overlapping in epilepsy and AD ( 212 ) or aMCI from which the conversion rate to AD is exceptionally high ( 110 ). On the other hand, while approximately two-thirds of all dementias are due to AD, mixed cohorts might also impact the observed prevalence of epilepsy and dementia due to AD.…”

“…A similar increase to that of amyloid burden was found for pTau in post-surgery brain resections collected from TLE patients with focal drug-resistant epilepsy ( 65 ). Moreover, a very recent review by Tombini et al ( 34 ) showed that TLE and AD patients share many pathophysiological associations starting with the presence of hallmark depositions of AD (Aβ plaques and NFTs, or their soluble forms), a similarity that is more robust for late-onset TLE cases ( 110 ).…”

Mechanisms Involved in Epileptogenesis in Alzheimer’s Disease and Their Therapeutic Implications

“…Indeed, multiple studies support a higher prevalence of mild cognitive impairment (MCI) in late-onset epilepsy (40-55%) [75,85] and in temporal lobe epilepsies (TLE) in which prevalence is up 60% [84]. The amount of temporomedial IEDs and hippocampal onset seizures correlate with progressive episodic memory decline in TLE [20,78,86]. In turn, up to 50% of LOEU patients have frequent multidomain, dysexecutive-predominant MCI with frequent involvement of visuospatial functions [9,87].…”