Older Adults With Epilepsy Experience Faster Cognitive Decline

February 11, 2021
Victoria Johnson
Victoria Johnson

Victoria Johnson, Assistant Editor for NeurologyLive, joined the MJH Life Sciences team in October 2020. Follow her on Twitter @_vic_j or email her at vjohnson@neurologylive.com

Mini-mental state exam scores declined significantly faster in adults with prevalent and incident epilepsy, while digit symbol substitution test scores declined significantly faster in prevalent epilepsy.

Recent study data suggest that older adults with prevalent and incident epilepsy had faster cognitive decline than those without epilepsy.

In modified mini-mental state exam (3MS) scores, adults with prevalent epilepsy had an estimated rate of decline compared to no epilepsy of 0.77 (95% CI, −1.11 to −0.44; P <.001) points per year and adults with incident epilepsy had an estimated rate of decline compared to no epilepsy of 1.47 (95% CI, −2.39 to −0.55; P = .002). The presence of both prevalent epilepsy and apolipoprotein E gene ε4 (APOE4) were associated with a 1.51-point faster annual decline (95% CI, −2.26 to −0.75; P <.001) in 3MS score than would be expected if there was no interaction between the 2 factors.

“In this longitudinal study of older adults, global cognitive function declined more rapidly in individuals with prevalent epilepsy (onset prior to age 65) and incident epilepsy (onset at age 65 or older) compared to those without epilepsy, even after adjusting for risk factors associated with cognitive decline,” first author Hyunmi Choi, MD, MS, associate professor, neurology, Columbia University Medical Center, and colleagues wrote.

“When we adjusted for APOE4 status, associations of prevalent and incident epilepsy with decline in 3MS were attenuated. We found that APOE4 status modified the relationship of prevalent epilepsy with 3MS such that epilepsy patients with an APOE4 allele had more rapid cognitive decline than would be expected if epilepsy and APOE4 acted independently,” they added.

Choi and colleagues analyzed 208 cases of prevalent epilepsy (present since earlier in life) and 21 incident (new onset) cases that underwent 3MS testing, as well as 207 cases of prevalent epilepsy and 16 incident cases that underwent Digit Symbol Substitution Testing (DSST). They included 5443 participants without epilepsy as controls. All participants had an average age of 73.2 years (standard deviation, 5.5) and 3146 (57.8%) were women. 

READ MORE: Characterizing Cognitive Impairment in Epilepsy: Chicken or the Egg?

They found that participants with prevalent epilepsy experienced a mean 1.1-point decline per year from baseline to year 4, while participants without epilepsy declined by a mean of 0.4 points per year from baseline to year 4. From year 4 to 8, participants with prevalent epilepsy declined by 2.0 points per year on average while participants without epilepsy declined by 1.2 points per year on average. 

Choi and colleagues also found that participants who developed incident epilepsy during follow-up had a mean decline in 3MS score of 2.1 points per year after epilepsy onset through year 4, and a 2.7 point average decline from year 4 to 8. Excluding for clinical stroke attenuated prevalent and incident epilepsy associations with 3MS score but they remained significant.

APOE4 was found to have significant interaction with prevalent epilepsy but not incident epilepsy. The significant increased rate of decline compared to adults without epilepsy remained in prevalent epilepsy but not incident epilepsy after adjusting for APOE4 status. Researchers found that adults with prevalent epilepsy but absence of APOE4 had an average annual decline in 3MS score of 0.6 (95% CI, 0.2-1.0) points, while those with prevalent epilepsy and APOE4 had an average annual decline of 2.5 (95% Ci, 1.8-3.1) points.

Choi and colleagues found that older adults with prevalent epilepsy had a significantly lower initial DSST score (P < .001) and faster rate of decline compared to those with no epilepsy, with an estimated annual point decline of 0.32 (95% CI, −0.52 to −0.13; P <.001). Participants with incident epilepsy were not found to have a significant difference in decline compared to those with no epilepsy (P = .261). Excluding those with clinical stroke showed that initial mean DSST score was still lower in those with prevalent epilepsy than those without, but rate of decline was no longer significantly different.

“Prevalent epilepsy was associated with faster decline in global cognitive ability, especially in the presence of APOE4, and with lower initial score and faster decline in processing speed. Incident epilepsy was associated with faster subsequent decline in global cognitive ability, although the decline became attenuated when adjusting for APOE4... Biological mechanisms to explain these association, and clinical implications of screening for APOE4 status in individuals with epilepsy of early onset should be explored in future studies,” Choi and colleagues concluded.

REFERENCE
Choi H, Thacker EL, Longstreth Jr WT, Elkind MSV, Boehme AK. Cognitive decline in older adults with epilepsy: The cardiovascular health study. Epilepsia. 2021. 62: 85- 97. doi: 10.1111/epi.16748