Active Cigarette Smoking in Cognitively-Normal Elders and Probable Alzheimer’s Disease is Associated with Elevated Cerebrospinal Fluid Oxidative Stress Biomarkers

Article type: Research Article

Authors: Durazzo, Timothy C.^{a; b; *} | Korecka, Magdalena^c | Trojanowski, John Q.^c | Weiner, Michael W.^{d; e} | O’ Hara, Ruth^{a; b} | Ashford, John W.^{a; b} | Shaw, Leslie M.^c | for the Alzheimer’s Disease Neuroimaging Initiative

Affiliations: [a] Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA | [b] Mental Illness Research and Education Clinical Centers and Sierra-Pacific War Related Illness and Injury Study Center VA Palo Alto Health Care System, Palo Alto, CA, USA | [c] Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Diseases Research, Perelman School of Medicine University of Pennsylvania, PA, USA | [d] Departments of Radiology and Biomedical Imaging, Psychiatry, Medicine, and Neurology, University of California, San Francisco, CA, USA | [e] Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA

Correspondence: [*] Correspondence to: Timothy C. Durazzo, PhD, War Related Illness and Injury Study Centers, Mental Illness Research and Education Clinical Centers (151Y), VA Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304, USA. Tel.: +1 650 493 5000/Ext. 62982; Fax: +1 650 852 3203; E-mail: [email protected].

Abstract: Neurodegenerative diseases and chronic cigarette smoking are associated with increased cerebral oxidative stress (OxS). Elevated F2-isoprostane levels in biological fluid is a recognized marker of OxS. This study assessed the association of active cigarette smoking with F2-isoprostane in concentrations in cognitively-normal elders (CN), and those with mild cognitive impairment (MCI) and probable Alzheimer’s disease (AD). Smoking and non-smoking CN (n = 83), MCI (n = 164), and probable AD (n = 101) were compared on cerebrospinal fluid (CSF) iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostane concentrations. Associations between F2-isoprostane levels and hippocampal volumes were also evaluated. In CN and AD, smokers had higher iPF2α-III concentration; overall, smoking AD showed the highest iPF2α-III concentration across groups. Smoking and non-smoking MCI did not differ on iPF2α-III concentration. No group differences were apparent on 8,12, iso-iPF2α-VI concentration, but across AD, higher 8,12, iso-iPF2α-VI level was related to smaller left and total hippocampal volumes. Results indicate that active cigarette smoking in CN and probable AD is associated with increased central nervous system OxS. Further investigation of factors mediating/moderating the absence of smoking effects on CSF F2-isoprostane levels in MCI is warranted. In AD, increasing magnitude of OxS appeared to be related to smaller hippocampal volume. This study contributes additional novel information to the mounting body of evidence that cigarette smoking is associated with adverse effects on the human central nervous system across the lifespan.

Keywords: Alzheimer’s disease, cigarette smoking, F₂-isoprostanes, hippocampus, mild cognitive impairment

DOI: 10.3233/JAD-160413

Journal: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 99-107, 2016