SAN DIEGO — Cognitive impairment can be a typical comorbidity in epilepsy, appearing in a significant number of older adults with temporal lobe epilepsy (TLE), the most common form of focal epilepsy, according to a new study.

A study team led by the University of California San Diego and including participation from the VA San Diego Healthcare System sought to characterize the nature and prevalence of cognitive disorders in older adults with TLE. Researchers compared cognitive profiles in those patients with amnestic mild cognitive impairment (aMCI). Results were published in the journal Epilepsia.1

Included in the study from the  Alzheimer’s Disease Neuroimaging Initiative were 71 older patients with TLE; of those 77 had aMCI, and 69 were normal aging controls (NACs), all 55‐80 years of age. Participants completed neuropsychological measures of memory, language, executive function, and processing speed.

Researchers applied an  actuarial neuropsychological method designed to diagnose MCI to individual patients to identify older adults with TLE who met diagnostic criteria for MCI (TLE‐MCI). They also performed a linear classifier to evaluate how well the diagnostic criteria differentiated patients with TLE‐MCI from aMCI. Also evaluated was the contribution of epilepsy‐related and vascular risk factors to cognitive impairment.

Ultimately, 43 patients (60%) met criteria for TLE‐MCI, i.e., demonstrating substantial deficits in both memory and language. Analyzed according to age at seizure onset, 63% of patients with an early onset – defined as younger than 50 – vs. 56% of those with late onset – defined as 50 or older —  met criteria for TLE‐MCI.

The authors advised that a classification model between TLE‐MCI and aMCI correctly classified 81.% (90.6% specificity, 61.3% sensitivity) of the cohort based on neuropsychological scores.

“Whereas TLE‐MCI showed greater deficits in language relative to aMCI, patients with aMCI showed greater rapid forgetting on memory measures,” they wrote. “Both epilepsy‐related risk factors and the presence of leukoaraiosis on MRI contributed to impairment profiles in TLE‐MCI.”

Researchers said their findings were significant, pointing out, “Although the underlying etiologies are unknown in many patients, the TLE‐MCI phenotype may be secondary to an accumulation of epilepsy and vascular risk factors, signal the onset of a neurodegenerative disease, or represent a combination of factors.”

Another study from the Alzheimer’s Disease Neuroimaging Initiative, also published in Epilepsia, reported that, compared to controls, TLE patients demonstrated abnormal measures of segregation (increased transitivity and decreased modularity) and integration (decreased global path efficiency). The authors also noted that aMCI patients displayed increased transitivity and decreased global path efficiency, but the differences were less pronounced than in TLE.2

“At the local level, TLE patients demonstrated decreased local path efficiency focused in the bilateral temporal lobes, whereas aMCI patients had a more frontal-parietal distribution,” the researchers wrote. “These results suggest that network disruption at the global and local level is present in both disorders, but global disruption may be a particularly salient feature in older adults with TLE. These findings motivate further research into whether these network changes have distinct cognitive correlates or are progressive in older adults with epilepsy.”

  1. Reyes A, Kaestner E, Edmonds EC, Christina Macari A, Wang ZI, Drane DL, Punia V, Busch RM, Hermann BP, McDonald CR; Alzheimer’s Disease Neuroimaging Initiative. Diagnosing cognitive disorders in older adults with epilepsy. Epilepsia. 2021 Feb;62(2):460-471. doi: 10.1111/epi.16780. Epub 2020 Dec 1. PMID: 33258159.
  2. Kaestner E, Reyes A, Wang ZI, Drane DL, Punia V, Hermann B, Busch RM, McDonald CR; Alzheimer’s Disease Neuroimaging Initiative. Topological alterations in older adults with temporal lobe epilepsy are distinct from amnestic mild cognitive impairment. Epilepsia. 2020 Nov;61(11):e165-e172. doi: 10.1111/epi.16703. Epub 2020 Oct 14. PMID: 33345333.