Everyone knows that smoking is bad for you. But there is some evidence, both epidemiological and molecular, that smokers are at reduced risk for neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Epidemiological evidence has come mainly from cohort studies, which many researchers claim are subject to bias, while molecular data have implicated the α7 nicotinic acetylcholine receptor as mediating any potential benefit of smoking (see ARF related news story for coverage of both issues). This week, two new papers inject fresh data into both veins of the debate.
First, the epidemiology. In the March 23 Neurology, the EURODEM Incidence Research Group, which includes principal investigators from Denmark, France, The Netherlands, and the UK, reports the results of a longitudinal study designed to assess the impact of smoking on the cognitive abilities of nondemented volunteers. First author A. Ott and colleagues enrolled more than 17,000 people over the age of 65 in the study. After an average of 2.3 years, over 9,000 of them were reevaluated with the Mini-Mental Stage Examination (MMSE), a commonly used cognitive test. Adjusting for a variety of parameters, including age, sex, and education, Ott found that those who never smoked fared much better in the test than did current or former smokers.
MMSE test scores in volunteers who had never smoked declined by an average of 0.03 points per year. The rate of decline was slightly higher in former smokers (0.06 points per year), but substantially higher in smokers (0.16 per year). In the last group, the number of cigarettes smoked positively correlated with the extent of the decline. The results suggest that far from being protective, smoking probably increases one's risk of suffering some sort of cognitive loss. This may not necessarily be due to a higher risk for AD, however, because as the authors point out, smoking may cause cerebral infarcts that could manifest as a loss in cognitive function.
In the Journal of Neurochemistry, Jun Tan and colleagues at the University of South Florida, report that the α7 nicotinic acetylcholine receptor (α7nAChR) may modulate the activation of microglia. Though the precise role played by these immune cells in neurodegenerative diseases is unclear, some researchers believe that they may exacerbate pathology under certain conditions (see ARF related news story). First author Douglas Shytle and colleagues tested cultured microglial cells for the receptor and found that both the messenger RNA and protein are expressed.
To test the physiological significance of this expression, Shytle determined if the receptor plays any role in the immune reactivity of the microglia. These cells are known to respond to immune challenge, such as lipopolysaccharide (LPS) stimulation, by the phosphorylation of proteins p44/42 and p38 MAP kinase, and by the release of the cytokine tumor necrosis factor α (TNFα). Shytle found that if the cells were first treated with nicotine or acetylcholine, then LPS-induced phosphorylation and release of TNFα were attenuated.
These results, the authors suggest, reveal a mechanism whereby nicotine may be neuroprotective, but they caution that this hypothesis needs to be tested in vivo before any conclusions can be made.—Tom Fagan