Lipid oxidation as a marker of apathy and executive dysfunction in patients at risk of vascular cognitive impairment

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AbstractBackgroundApathy and executive function decline are hallmarks of vascular dysfunction in neurodegeneration and cognitive impairment. People with mild vascular cognitive impairment (mVCI) display a combined etiology of both cognitive impairment and vascular comorbidities; hence, patients with vascular risk factors are at risk for mVCI. The co‐occurrence of apathy and executive dysfunction is prevalent; however, the physiological pathway underlying these manifestations is yet to be investigated. Oxidative stress is often present in vascular dysfunction. This study investigated the relationship between oxidative stress, specifically markers of lipid oxidation, apathy, and executive dysfunction in patients at risk of mVCI.MethodPatients at risk of mVCI were recruited from a population of patients with coronary artery disease in a Cardiac Rehabilitation Program. Apathy was assessed using the Apathy Evaluation Scale and executive function with Trial Making Test B, phonemic fluency test and animal naming test. Fasting blood was collected and serum concentrations of early and late lipid oxidation markers, lipid hydroperoxides (LPH) and 8‐isoprostane (8‐ISO) respectively, were measured.ResultParticipants (n=206, Age= 63.0±7.5, 80% men, total years of education= 15.9±3.4, AES score= 28.3±8.8, composite z score for EF= 0±1) demonstrated significantly different ratios of late to early lipid oxidation markers (8‐ISO/LPH) between groups (F(3, 202) = 10.915, p <0.001) with increasing levels in the following order: no apathy or executive dysfunction, only executive dysfunction, only apathy, and both apathy and executive dysfunction. A multivariate linear regression model adjusting for demographics found that lipid oxidation was significantly associated with apathy (B= 4.63, p < 0.001) and executive function (B= ‐0.19, p= 0.018); however, when controlling for both demographics and vascular risk factors, lipid oxidation was significantly associated with apathy alone (B= 3.11, p= 0.002).ConclusionThe results highlight an important involvement of lipid oxidation in the co‐occurrence of apathy and executive dysfunction in patients at risk of mVCI. Our results show that increased oxidative stress may contribute to the development of apathy, which may relate to why apathy is a strong risk factor for progression to dementia in at‐risk populations.