Abstracts

Rationale: Several laboratory biomarkers of vascular and metabolic health are known to be associated with accelerated cognitive aging in the general population. The purpose of this investigation was twofold: 1) compare aging persons with chronic epilepsy to unaffected controls on vascular and metabolic biomarkers, and 2) examine the relationship between these biomarkers and cognitive function in participants with epilepsy. Methods: The study group consisted of 192 participants including 40 individuals with early onset (<20) chronic epilepsy and 152 controls, mean age 54.6 and 55.3 respectively. The groups were comparable in age, gender, education, number of APOE e4 alleles, and ethnicity. Biomarkers of vascular and metabolic health included diastolic and systolic blood pressure, body mass index (BMI), insulin resistance (HOMA-IR), high sensitivity c-reactive protein (hs-CRP), homocysteine, interlukin-6 (IL-6), creatinine, vitamin B-12, cholesterol (HDL and LDL) and glucose. All subjects underwent comprehensive neuropsychological assessment with a test battery previously demonstrated via factor analysis to be characterized by verbal ability, spatial ability, immediate memory, verbal learning/delayed recall, speed and flexibility, and working memory. Results: Compared to controls, aging participants with chronic epilepsy exhibited abnormalities in BMI (p=0.049), hs-CRP (p=0.046), HOMA-IR (p=0.0040), and glucose (p=0.03). HDL was marginally lower in the epilepsy group (p=.069). All cognitive factor scores were significantly lower in the participants with epilepsy (all p's <0.0001). Biomarker-cognition relationships were examined in the epilepsy group and significant associations were found. Higher HOMA-IR was correlated with poorer performance on the immediate memory (-0.35, p=0.03) and visual spatial (r-0.35, p=0.03) factor scores with a trend of lower working memory factor score (r=-0.28, p=0.09). Elevated hs-CRP was correlated with poorer visual spatial (r=-0.34, p=0.035) and verbal ability (r=-0.31, p=0.06) factor scores. Elevated BMI was associated with poorer speed and flexibility (r=-0.31, p=0.04), visual spatial (r=-0,50, p=0.001) and verbal ability (-0.36, p=0.02) factor scores. Lower HDL was associated with poorer verbal learning/delayed memory (r=-0.41, p=0.01), speed and flexibility (r=-0.34, p=0.043), and working memory (r=-0.42, p=0.008) factor scores. Conclusions: Abnormalities in biomarkers of vascular and metabolic health are known to be associated with cognitive morbidity in the general aging population. Several of these biomarkers are not only abnormal in aging persons with chronic epilepsy compared to controls, but are also related to more impaired cognitive status. Poorer cognitive function in epilepsy is specifically related to abnormal BMI, insulin resistance, inflammatory markers, and lipid profile.