Abstract
High serum uric acid (UA) levels are associated with numerous vascular risk factors, and vascular disease, that predispose patients to cognitive impairment, yet UA is also a major natural antioxidant and higher levels have been linked to slower progression of several neurodegenerative disease. In-order to test the association between UA and subsequent cognitive performance among patients that carry a high vascular burden, UA levels were determined by calorimetric enzymatic tests in a sub-cohort of patients with chronic cardiovascular disease who previously participating in a secondary prevention trial. After an average of 9.8±1.7 years, we assessed cognitive performance (Neurotrax Computerized Cognitive Battery) as well as cerebrovascular reactivity (CVR) and common carotid intima-media thickness (IMT). Among 446 men (mean age 62.3±6.4 yrs) mean UA levels were 5.8±1.1 mg/dL. Adjusted linear regression models revealed that low UA levels (bottom quintile) were associated with poorer cognitive performance. Adjusted differences between the bottom quintile and grouped top UA quintiles were (B coefficient±SE) −4.23±1.28 for global cognitive scores (p = 0.001), −4.69±1.81 for memory scores (p = 0.010), −3.32±1.43 for executive scores (p = 0.020) and −3.43±1.97 for visual spatial scores (p = 0.082). Significant difference was also found for attention scores (p = 0.015). Additional adjustment for impaired CVR and high common carotid IMT slightly attenuated the relationship. Stronger UA effect on cognitive performance was found for older (age>65) patients with significant age interaction for global cognitive score (p = 0.016) and for executive (p = 0.018) and attention domains (p<0.001). In conclusion, we demonstrate that low UA levels in patients with preexisting cardiovascular disease are associated with poorer cognitive function a decade later. These findings lend support to the hypothesis that oxidative stress may be involved in the pathogenesis of age-associated cognitive impairment.
Highlights
There are a plethora of epidemiological studies linking high serum uric acid (UA) levels with increased risk of vascular disease [1,2,3]
In a cross-sectional analysis conducted on a subsample of the Rotterdam study participants, high UA levels were associated with white matter atrophy and with poorer cognition [12]
Decreasing quintiles of UA were associated with higher rates of impaired cerebrovascular reactivity (CVR) and high common carotid intima-media thickness (IMT)
Summary
There are a plethora of epidemiological studies linking high serum uric acid (UA) levels with increased risk of vascular disease [1,2,3]. High UA levels are associated with major vascular risk factors such as hypertension [4], chronic kidney disease [5], the metabolic syndrome and diabetes [6], as well as with cerebral ischemic white matter changes [7] and carotid atherosclerosis [8] that all predispose to vascular cognitive impairment. In the Rotterdam Study, an association was found between higher UA levels and better global cognitive, executive and memory functions later in life. In a cross-sectional analysis conducted on a subsample of the Rotterdam study participants, high UA levels were associated with white matter atrophy and with poorer cognition [12]
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