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.

Keywords: brain atrophy; dementia; mild cognitive impairment; structural MRI; temporal lobe epilepsy.

Figure 1

Overlapping patterns of MTL cortical atrophy in TLE and amnestic MCI. (A and B) Patterns of cortical thinning for both TLE and amnestic MCI (aMCI) relative to healthy control subjects (HC). Blue denotes cortex significantly thinner than healthy controls for each patient group. Both patient groups showed prominent cortical thinning in bilateral medial temporal lobe (MTL) regions highlighted by dashed lines. (C–F) To confirm the robustness of the surface analyses, region of interest analyses were performed using the Desikan-Killiany parcellation. Similar to the surface analyses, significant thinning was found for patient groups relative to healthy control subjects in MTL regions. Teal = TLE; purple = amnestic MCI; and dark grey = healthy controls. *P < 0.05, **P < 0.01. PHC = parahippocampal.

Figure 2

Temporal lobe atrophy is at least as widespread in patients with LO-TLE compared to EO-TLE. (A and B) Patterns of cortical thinning for both LO-TLE and EO-TLE relative to healthy controls (HC). Blue denotes cortex significantly thinner than healthy controls for each patient group. Teal denotes clusters of thinning that were subthreshold after cluster correction in the EO-TLE group. (C and D) Region of interest analyses performed using the Desikan parcellation confirm the robustness of the surface patterns. Light teal = EO-TLE; dark teal = LO-TLE; purple = amnestic MCI; dark grey = healthy controls. *P < 0.05, **P < 0.01. PHC = parahippocampal.

Figure 3

Neuropsychological performance across patient groups. (A–C) Distribution of z-scores across neuropsychological tests for EO-TLE, LO-TLE, and amnestic MCI (aMCI). Solid line indicates average performance and dotted line indicates impairment at 1.5 SD below the mean of healthy controls (HC). BNT = Boston Naming Test; CF = Category Fluency; RAVLT = Rey Auditory Verbal Learning Test.