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Frans_Jozef
Sunday, January 23rd, 2005, 10:47 AM
Cigarette Smoking May Lower Rates of Neurodegenerative Diseases like Parkinson's and Alzheimer's

Posted By: News-Medical (editor@news-medical.net) in Medical Study News Published: Monday, 15-Mar-2004




While the health risks of tobacco are well known, several studies have shown that people with a history of cigarette smoking have lower rates of neurodegenerative diseases like Parkinson's and Alzheimer's disease. However, the explanations for nicotine's neuroprotective effects continue to be debated.

Now a team of neuroscientists at the University of South Florida College of Medicine presents new evidence of an anti-inflammatory mechanism in the brain by which nicotine may protect against nerve cell death. Their study was published today in the Journal of Neurochemistry.

In laboratory experiments, the researchers demonstrated that nicotine inhibits activation of brain immune cells known as microglia. Chronic microglial activation is a sign of brain inflammation that is a key step in nerve cell death. The researchers also identified the specific site, the alpha-7 acetylcholine receptor subtype, to which nicotine binds to block microglial activation.

"We propose that nicotine's ability to prevent overactivation of microglia may be additional mechanism underlying nicotine's neuroprotective properties in the brain," said USF neuroscientist R. Douglas Shytle, PhD, lead author of the study.

"This finding lets us explore a new way of looking at neurodegenerative diseases like Alzheimer's," said Jun Tan, PhD, MD, principal investigator for the study. "A better understanding of the therapeutic aspects of nicotine may also help us develop drugs that mimic the beneficial action of nicotine without its unwanted side effects."

Nicotine mimics the neurotransmitter acetylcholine, a chemical messenger that is critical to communication between brain cells. Acetylcholine is the major neurotransmitter lost in Alzheimer's disease.

The prevailing hypothesis among researchers is that nicotine helps protect the brain by binding to nicotinic acetylcholine receptors that sit on the end of nerve terminals. This action by nicotine, similar to turning up the volume of a radio signal, causes brain cells to increase the release of neurotransmitters depleted in diseases like Alzheimer's and Parkinson's.

The USF study suggests that nicotine may also protect the brain through another, more indirect route -- by quelling the hyperactivity of immune cells (microglia) that have turned against the brain.

In the normal, healthy brain microglia support and maintain neurons. They also help wipe up excess beta amyloid protein that accumulates in the brain with aging.

"Microglia can be your best friend or your worst enemy depending on the signals they receive," Dr. Shytle said. "The analogy is that you keep talking to them they will take care of you, but if you stop talking they are more likely to get aggressive and have a toxic effect on the brain."

The USF researchers hypothesize that acetylcholine acts as an endogenous anti-inflammatory substance to help prevent microglia from attacking the brain. This neurotransmitter may consistently signal brain's immune system that everything is OK -- no need to activate more microglia, Dr. Shytle said. But, he said, if the neurons that communicate using acetylcholine begin to die and the acetylcholine signal fades, the microglia may become hyperactive and give rise to chronic inflammation that further aggravates the destruction of brain cells.

"In those at risk for Alzheimer's and other neurodegenerative diseases, nicotine may act much like the neurotransmitter acetylcholine. It may send signals to help suppress microglial immune response and limit excessive brain inflammation," Dr. Tan added.


http://www.news-medical.net/?id=22

Frans_Jozef
Sunday, January 23rd, 2005, 10:48 AM
Smoking, coffee, and Parkinson's Disease

Systematic review (http://www.jr2.ox.ac.uk/bandolier/band107/b107-5.html#Heading3) Cigarette smoking (http://www.jr2.ox.ac.uk/bandolier/band107/b107-5.html#Heading4) Coffee drinking (http://www.jr2.ox.ac.uk/bandolier/band107/b107-5.html#Heading5) Comment (http://www.jr2.ox.ac.uk/bandolier/band107/b107-5.html#Heading6)
Healthy living messages are usually relatively simple, and involve not smoking, eating fruit and vegetables, taking exercise and perhaps the odd glass of wine. That message does for heart disease, and cancer, and bone density and a raft of other things. It all gets more difficult when some of those lifestyle elements thought not to be good for us are actually shown to have some benefits. An example is the association between smoking and coffee drinking and the risk of Parkinson's disease [1].

Systematic review

An extensive search of several databases sought to identify studies associating smoking, coffee and Parkinson's disease. For inclusion studies had to have a case-control or cohort design, present original data, have Parkinson's disease diagnosed by a physician as the outcome, and attempt to ascertain exposure before the diagnosis.

Cigarette smoking

The 44 case-control studies involved 6,814 cases and 11,791 controls. Controls were often friends or relatives, patients with other diseases, or community controls, or a combination of these. The four cohort studies involved 409 cases in a total cohort size of just under 190,000.

Compared with never having smoked, cigarette smoking reduced the risk of developing Parkinson's disease (Table 1). There was a greater reduction for current smokers than for all smokers or past smokers. The magnitude of the risk reduction was similar for case-control and cohort studies. Each additional 10 pack years smoked was associated with a risk reduction of about 15%.

Table 1: Summary of results on smoking and coffee drinking and risk of Parkinson's disease

Status

Type of study

Number of studies

Relative risk
(95% CI)

Ever smoked All studies 45 0.58 (0.54 to 0.63)
Case-control 41 0.59 (0.55 to 0.65)
Cohort 4 0.52 (0.42 to 0.64) Past smokers All studies 16 0.80 (0.69 to 0.93) Current smokers All studies 18 0.39 (0.32 to 0.47) Coffee drinker All studies 12 0.69 (0.59 to 0.80)
Case-control 8 0.66 (0.52 to 0.83) Cohort 4 0.70 (0.56 to 0.88) Relative risk is by random effects model
Coffee drinking

The eight case-control studies involved 1,440 cases and 4,016 controls. The four cohort studies involved 321 cases in a total cohort size of just under 190,000.

Compared with people who did not drink coffee, drinking coffee reduced the risk of developing Parkinson's disease (Table 1). The magnitude of the reduction was the same in case-control and cohort studies, and studies that adjusted for smoking. The evidence concerning the effect of the amount of coffee was mixed, though the authors estimated a risk reduction of 10% for each additional cup of coffee per day.

Comment

The results of this meta-analysis suggest that current smokers have a 60% lower risk of Parkinson's disease and coffee drinkers a 30% lower risk. The results were consistent across study design and geographical setting. Smokers who drink a lot of coffee will be given succour by these findings, but not for long.

First, Parkinson's disease occurs in only 1 in 200 of the elderly population, and 1 in 1,000 of the adult population. With cigarette smoking, the balance of risk is still negative, taking increased risks of cancer, and heart and respiratory disease into account.

Second, the association found in this meta-analysis does not prove that there is a cause and effect. There may be, but other possibilities exist and there is an interesting discussion about them in this paper. For instance, the diagnosis of Parkinson's disease could be more frequently omitted from death certificates and medical records of smokers (information bias). Another explanation may be that there is an increased mortality of younger smokers from causes other than Parkinson's disease (selection bias). Or again, smokers and sufferers of Parkinson's disease may share common genetic or environmental causes of which we are presently unaware (confounding). Perhaps patients with subclinical Parkinson's disease are less likely to start smoking or more likely to stop.

The authors of the paper argue persuasively against these possibilities, and suggest that smoking might protect against Parkinson's disease. We need to watch this space.

References:



MA Hernán et al. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Annals of Neurology 2002 52: 276-284.


http://www.jr2.ox.ac.uk/bandolier/band107/b107-5.html