Smoking and Alzheimer's disease

THE LAST GREAT TOBACCO CLAIM

by Phantomimic

All rights reserved © RAGG

For decades the tobacco industry mustered all its financial, legal and

political clout to fight tooth and claw against the concept that their product

was harmful. Only in 1998 with the release of the previously secret internal

tobacco industry documents, as a result of the Master Settlement Agreement,

were the types of strategies the industry employed finally revealed to the

general public. The main goal was to raise controversy and make any anti-

tobacco evidence look tentative. To this end, the tobacco industry sponsored

research designed to produce findings that were favorable to its position

while often hiding the extent of its involvement. The industry also

disseminated favorable research to the lay press and policy makers while

suppressing research that did not support its position. Fortunately nowadays

it is widely acknowledged as a rock solid fact that smoking is harmful to a

person's health.

Most people now know that smoking increases the risk of lung cancer. But

smoking also increases the risk of cardiovascular and cerebrovascular

problems, atherosclerosis and stroke. For these reasons, smoking would be

expected to be a risk factor when it comes to Alzheimer's disease. In

Alzheimer's disease the metabolism of the brain is compromised. Adding on

the myriad of health problems due to smoking would certainly not be

considered to be helpful. This is especially relevant considering that

Alzheimer's disease is most common in elderly people who often have a host

of age-related health problems. Indeed, as expected, several studies have

found that smoking increases the risk of Alzheimer's disease.

But there was a paradox.

Among the signaling systems that are compromised in the brain of

Alzheimer's patients is the so called cholinergic system and there are

receptors within this system that can be stimulated by nicotine, which is

present in tobacco. Thus, in theory, nicotine could "boost" this system to

compensate (at least for a certain amount of time) for its deterioration in

Alzheimer's disease. Nicotine has also been found to increase alertness and

enhance learning and memory. So, the argument grew that cigarettes, being

in effect a nicotine delivery system, could be helpful in Alzheimer's disease.

Indeed, several studies have found that smoking in different contexts reduces

the risk of Alzheimer's disease and this notion has made its way to the lay

press and cyberspace.

But these claims have been controversial as many consider that the harmful

chemicals in tobacco would likely outweigh any positive effects of nicotine,

and even if nicotine were found to be beneficial there are safer and more

efficient means of delivering it to the body than through cigarette smoke.

However, the fact remains that, for the majority of people, the most common

nicotine delivery vehicle is smoking. Not surprisingly the tobacco industry

has funded research into this matter for the past two decades.

In a recent article published in the Journal of Alzheimer's Disease by Janine

Cataldo, Judith Prochaska and Staunton Glantz, researchers of the University

of California, San Francisco (UCSF), the authors did something that

previous researchers in the field of Alzheimer's disease had not done.

Normally when you perform a statistical evaluation of the scientific

literature regarding a certain topic you want to account for all the variables

that can affect the outcome of the studies you are reviewing. This is called

"controlling a variable", which is important, otherwise you end up

comparing apples and oranges. What the UCSF researchers did is that they

"controlled" for several variables among which was the affiliation of the

authors of the studies with the tobacco industry. To do this they went

through thousands of previously secret tobacco industry documents and

identified those studies that had authors who were involved with the tobacco

industry within ten years of publication of the study.

What was the result?

The authors reviewed 43 studies of smoking and Alzheimer's disease that

met their inclusion criteria which were: 1) the study had to be published, 2)

it had to use Alzheimer's disease as the outcome (not dementia or cognitive

decline), 3) use human subjects (brain tissue excluded), 4) have a

measurement of smoking (i.e. ever smoker, current smoker, never smoke)

and 5) have a clearly stated study design (case control or cohort study). Of

these 43 studies, 11 (26%) were conducted by tobacco industry affiliated

investigators but in only 3 of them was the affiliation disclosed. If all 43

studies were combined without controlling for any variables (mixing apples

and oranges) the overall result was that smoking had no effect on

Alzheimer's disease yielding a risk ratio of 1.05 (1 = no risk).

The authors first focused on a particular type of study called a "cohort"

study. This is a study where a group of smokers and non-smokers are

followed over time and evaluated for the development of Alzheimer's

disease. In the area of epidemiology cohort studies are widely considered the

most scientifically valid type of studies. They found that when they

controlled for several variables including tobacco industry affiliation (thus

separating the apples from the oranges), the risk-ratio of a current or ever

tobacco smoker developing Alzheimer's disease was 1.72. In other words a

current or ever smoker had a 72% higher risk of developing Alzheimer's

disease than a non-smoker.

The authors then focused on a second type of study called a "case control"

study where a group of individuals with Alzheimer's disease is compared for

"exposure to smoking" to a matched group of individuals without

Alzheimer's disease. It was important to distinguish between cohort and case

control studies because case control studies are more prone to bias that can

underestimate the risk of Alzheimer's disease. The authors found that the

case control studies with no tobacco industry affiliation yielded a non-

significant risk ratio of 0.91, whereas the studies with tobacco industry

affiliation yielded a statistically significant ratio of 0.86, meaning that

smoking was found to be "protective".

Finally the authors performed an evaluation of past reviews of the scientific

literature investigating the relationship between smoking and Alzheimer's

disease. Of the 10 systematic reviews the authors examined there were 6

reviews performed by scientists with no tobacco industry affiliation. Of

these 6 reviews, 1 found no clear effect, 2 found no protective effect of

smoking and 3 found smoking to be a significant risk factor. The 4 reviews

performed by scientists with known tobacco industry affiliation all

concluded that smoking protected against Alzheimer's disease.

So overall "type of study" and "researchers with ties to the tobacco industry"

were variables associated with lower risk estimates, the latter to a much

greater extent than the former, but when these variables were controlled for,

a clear effect of smoking on Alzheimer's disease emerged.

The fact that tobacco industry sponsored research favors the industry's

position is nothing new. For example, in a 1998 evaluation by Deborah

Barnes and Lisa Bero of 106 scientific literature reviews regarding passive

smoking they found that the only factor associated with whether a review

concluded that passive smoking is not harmful to health was whether its

authors were associated with the tobacco industry. But the UCSF study

described in this article and others sure to follow will hopefully mean the

end to one of the last great lingering claims associated with smoking: that it

is protective in Alzheimer's disease.

One last note, Ronald Reagan is one of the most visible personalities to have

developed Alzheimer's disease, and he was a smoker like many celebrities of

his time (although I understand he quit when he became governor of

California). This is the only reason I chose his image for this article.

Epidemiology is a population-based science, it cannot predict or assert

whether an individual will develop or has developed Alzheimer's disease due

to smoking.

References

Cataldo JK, Prochaska JJ, Glantz SA. (2010) Cigarette smoking is a risk

factor for Alzheimer's Disease: an analysis controlling for tobacco industry

affiliation. J Alzheimers Dis. 2010;19(2):465-80.

http://www.ncbi.nlm.nih.gov/pubmed/20110594

Deborah E. Barnes and Lisa A. Bero (1998) Why Review Articles on the

Health Effects of Passive Smoking Reach Different Conclusions. JAMA.

1998;279:1566-1570.

http://jama.ama-assn.org/cgi/reprint/279/19/1566

Lisa A. Bero, 2005, Tobacco Industry Manipulation of Research, Public

Health Reports, March–April, Volume 120, pp. 200-208.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1497700/pdf/15842123.pdf

The secret tobacco industry document site has some eyebrow-raising

http://legacy.library.ucsf.edu/

The picture is from Wellmedicated.com, visit the web site for some

unbelievable cigarette adds from the days of yore.

http://wellmedicated.com/lists/40-gorgeous-vintage-tobacco-advertisements/

These pictures were in turn taken from from SA_Steve's Flickr.com photo

stream of vintage tobacco advertising.

http://www.flickr.com/photos/sa_steve/sets/72157615938880840/

If you liked this essay you may be interested in:

Visiting my website: Phantomimic's Website

Following me on Twitter: Phantomimic on Twitter

Liking my Facebook Page: Phantomimic on Facebook

Thank you! : ^ )