Lipid Peroxidation as a Marker of Apathy and Executive Dysfunction in Patients at Risk for Vascular Cognitive Impairment

Article type: Research Article

Authors: Bawa, Kritleen K.^{a; b} | Ba, Joycelyn^a | Kiss, Alex^{c; d} | Wang, RuoDing^{a; b} | Feng, Vivian^{a; b; e} | Swardfager, Walter^{b; e} | Andreazza, Ana^e | Gallagher, Damien^f | Marotta, Giovanni^g | Herrmann, Nathan^{a; b; f} | Lanctôt, Krista L.^{a; b; e; f; *}

Affiliations: [a] Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada | [b] Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada | [c] ICES, Sunnybrook Research Institute, Toronto, ON, Canada | [d] Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada | [e] Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada | [f] Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada | [g] Division of Geriatric Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Correspondence: [*] Correspondence to: Krista Lanctôt, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room FG 21, Toronto, ON M4N 3M5, Canada. E-mail: Krista.Lanctot@sunnybrook.ca.

Abstract: Background:The co-occurrence of apathy and executive dysfunction, a correlate of vascular cognitive impairment (VCI), is highly prevalent, yet facilitating factors are largely unknown. Objective:This study investigates the relationship between lipid peroxidation, apathy, and executive dysfunction in patients at risk for VCI. Methods:In participants with coronary artery disease, who are at a high risk of VCI, apathy (Apathy Evaluation Scale), and executive function (composite z-score based on age and education population norms from trails making test B, animal naming, and phonemic fluency tests) were assessed. Serum concentrations of an early (lipid hydroperoxide (LPH)) and late (8-isoprostane (8-ISO)) lipid peroxidation marker, were measured and the 8-ISO/LPH ratio was calculated. Results:Participants (n = 206, age±SD = 63.0±7.5, 80% men, total years of education = 15.9±3.4, AES score = 28.3±8.8, executive function = 0±1) demonstrated significantly different 8-ISO/LPH ratios 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 (executive function composite score≤–1), only apathy (AES≥28), and both apathy and executive dysfunction. A model adjusting for demographics showed that lipid peroxidation was associated with both apathy (B(SE) = 4.63 (0.954), t = 4.852, p < 0.001) and executive function (B(SE) = –0.19 (0.079), t = –2.377, p = 0.018). However, when controlling for both demographics and vascular risk factors, lipid peroxidation was associated with only apathy (B(SE) = 3.11 (0.987), t = 3.149, p = 0.002). Conclusion:The results highlight a potentially important involvement of lipid peroxidation in the co-occurrence of apathy and executive dysfunction in those at risk for VCI.

Keywords: Apathy, cardiac rehabilitation, cognition, cognitive dysfunction, coronary artery disease, executive function, lipid peroxidation, oxidative stress

DOI: 10.3233/JAD-220274

Journal: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 733-743, 2022