Epilepsy, Vascular Risk Factors, and Cognitive Decline in Older Adults: The Cardiovascular Health Study

Abstract

Background and objectives: Recent studies have shown that global cognitive ability tends to decline faster over time in older adults (≥65 years) with epilepsy compared with older adults without epilepsy. Scarce data exist about the role of vascular risk factors (VRFs) on cognitive course in epilepsy. We assessed whether the associations of individual VRFs with cognitive trajectory differed depending on the presence of prevalent epilepsy.

Methods: The Cardiovascular Health Study is a population-based longitudinal cohort study of 5,888 US adults aged ≥65 years. Cognitive function was assessed annually with modified Mini-Mental State Examination (3MS; global cognitive ability) and Digit Symbol Substitution Test (DSST; information processing speed). We used linear mixed models to estimate the individual and joint associations of epilepsy and VRFs with cognitive decline by modeling epilepsy × VRF interactions one by one, each adjusted for all other VRFs considered, including demographics, health behaviors, clinical characteristics, and comorbid diagnoses. From these models, we estimated excess mean cognitive decline due to interaction of epilepsy with each VRF.

Results: We observed excess mean decline in global cognitive ability (3MS) due to interactions of epilepsy with hypertension (6.6 points greater mean 8-year decline than expected if no interaction; 95% CI 1.3-12.0) and with abstaining from alcohol (5.8 points greater than expected; 95% CI 0.3-11.3). We also observed excess mean decline in information processing speed (DSST) due to interactions of epilepsy with prior stroke (18.1 points greater mean 9-year decline than expected; 95% CI 7.6-28.5), with abstaining from alcohol (6.1 points greater than expected; 95% CI 2.5-9.8), and with higher triglyceride levels (2.4 points greater than expected per SD; 95% CI 0.4-4.3).

Discussion: Associations of some VRFs with cognitive decline in older adults are stronger in the presence of epilepsy, suggesting a need for greater attention to vascular protection for preserving brain health in older adults with epilepsy.

Figure 1. Trajectories of the Mean 3MS Score by Prevalent Epilepsy and Selected Vascular Risk Factor Status

(A) Hypertension. (B) Alcohol abstention. (C) Coronary heart disease. (D) Current smoking. Estimates adjusted for age, sex, race, education, smoking, alcohol use, body mass index, waist circumference, systolic blood pressure, triglycerides, HDL cholesterol, depressive symptoms, self-rated health, diabetes, CHD, atrial fibrillation, heart failure, stroke, and chronic kidney disease. 3MS = modified Mini-Mental State Examination; CHD = coronary heart disease; HDL = high-density lipoprotein.

Figure 2. Excess Mean 8-Year Decline in the 3MS and 9-Year Decline in DSST Scores Due to Interactions of All Vascular Risk Factors Examined With Epilepsy

Horizontal bars accompanying each estimate are 95% CIs. Contrasts across risk factor levels are age per SD increment; men vs women; Black race vs White race; no post-high school education vs any; years of education through 12th grade per SD decrement; former smoking vs never; current smoking vs never; alcohol abstaining vs 4.9 drinks/week; drinks/week per SD increment among drinkers only; BMI per SD increment; waist circumference per SD increment; SBP per SD increment; triglycerides per SD increment; HDL cholesterol per SD decrement; depressive symptoms per SD increment; fair/poor health vs good/excellent; and each comorbidity diagnosis vs not. Each estimate adjusted for all other risk factors listed in the figure. 3MS = modified Mini-Mental State Examination; AF = atrial fibrillation; BMI = body mass index; CHD = coronary heart disease; CKD = chronic kidney disease; DSST = Digit Symbol Substitution Test; HDL = high-density lipoprotein; HF = heart failure; HS = higher secondary; SBP = systolic blood pressure.

Figure 3. Trajectories of the Mean DSST Score by Prevalent Epilepsy and Selected Vascular Risk Factor Status

(A) History of stroke. (B) Alcohol abstention. (C) Triglyceride levels. (D) HDL cholesterol levels. Estimates adjusted for age, sex, race, education, smoking, alcohol use, body mass index, waist circumference, systolic blood pressure, triglycerides, HDL cholesterol, depressive symptoms, self-rated health, diabetes, CHD, atrial fibrillation, heart failure, stroke, and chronic kidney disease. CHD = coronary heart disease; DSST = Digit Symbol Substitution Test; HDL = high-density lipoprotein.