History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress

• Background: Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F-2-isoprostane biomarkers of OxS. Methods: Elders with a lifetime history of smoking (smokers; n = 50; 75 +/- 5 years of age; 34 +/- 28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n = 61; 76 +/- 6 years of age) on CSF iPF(2 alpha)-III and 8,12, iso-iPF(2 alpha)-VI F-2-isoprostanes levels. F-2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F-2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated. Results: Smokers showed higher iPF(2 alpha)-III level than never-smokers. An age x smoking status interaction was observed for 8,12, iso-iPF(2 alpha)-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF(2 alpha)-VI concentration was associated with smaller hippocampal volume, and greater iPF(2 alpha)-III level was related to greater pack years. Conclusions: This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F-2-isoprostane levels and greater age-related increases in F-2-isoprostanes, and that higher F-2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Cigarette smoking

Oxidative stress

Isoprostanes

Hippocampus

Cerebrospinal fluid

Elder adults

SURFACE-BASED ANALYSIS

HUMAN CEREBRAL-CORTEX

ALZHEIMERS-DISEASE

TOBACCO-SMOKE

CARDIOVASCULAR-DISEASE

LIPID-PEROXIDATION

UNITED-STATES

HUMAN URINE

RISK-FACTOR

BACOSIDE-A

Substance Abuse

Psychiatry

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