Cigarette smoking may increase risk for Alzheimer’s disease

Cigarette smoking appeared linked to increased amounts of Alzheimer’s disease risk biomarkers, according to results of a case-control study published in JAMA Network Open.

“Evidence from epidemiological studies and meta-analyses have indicated that cigarette smoking is significantly associated with the risk of neurodegenerative disorders, including Alzheimer disease and dementia,” Yanlong Liu, PhD, of the School of Mental Health at Wenzhou Medical University in China, and colleagues wrote. “It has been reported that heavy smoking is associated with a greater than 100% increase in risk [for] dementia and [Alzheimer’s disease] after 2 decades of exposure. With memory loss and cognitive deficit, [Alzheimer’s disease] is among the most devastating brain disorders for older individuals.”

Results of an animal model of Alzheimer’s disease suggested that cigarette smoking may exacerbate amyloid pathology. Other studies demonstrated that measuring amyloid-beta 42 levels in cerebrospinal fluid (CSF) may offer diagnostic specificity for Alzheimer’s disease, with results of human studies showing a strong association between high CSF amyloid-beta 42 levels and mild cognitive impairment related to Alzheimer’s disease.

Liu and colleagues sought to investigate the link between cigarette smoking and CSF biomarkers of neurodegeneration, neuroinflammation, neuroprotection and oxidation. They analyzed these biomarkers among 191 adult men in China both with and without significant cigarette exposure. The nonsmoking group included 104 participants who did not smoke and had no history of substance use disorder or dependence, and the active smoking group included 87 participants who consumed 10 or more cigarettes daily for 1 year. The investigators collected 5-mL samples of CSF via routine lumbar puncture conducted prior to anterior cruciate ligament reconstruction surgery. Using CSF levels of amyloid-beta 42, they assessed for tumor necrosis factor alpha, brain-derived neurotrophic factor, total superoxide dismutase and nitric oxide synthase.

The nonsmoking group was younger, had more education and had lower BMI vs. the active smoking group. Results showed significantly lower mean CSF levels of amyloid-beta 42 and tumor necrosis factor alpha, as well as higher brain-derived neurotrophic factor, total superoxide dismutase, total nitric oxide synthase, inducible nitric oxide synthase and constitutive nitric oxide synthase, among the active smoking vs. nonsmoking group. Further, those in the smoking groups aged 40 years or older exhibited a negative correlation between total superoxide dismutase levels and amyloid-beta 42 levels. Those who smoked 20 cigarettes or more per day exhibited a positive correlation between tumor necrosis factor alpha and amyloid-beta 42 levels. The link between tumor necrosis factor alpha and amyloid-beta 42 levels was stronger than that of total superoxide dismutase and amyloid-beta 42 production.

“Cigarette smoking was associated with CSF biomarkers of neurodegeneration, neuroinflammation and oxidation,” Liu and colleagues wrote. “These are associated with risk [for Alzheimer’s disease].”