Smoking and the brain: No good evidence exists that smoking protects
against dementia

Smoking prevents dementia? Smoking causes dementia? Over the past decade a
succession of research findings has produced apparently conflicting
evidence on this question. In the early 1990s results from case-control and
family studies suggested a protective effect. 1 2 The findings were widely
reported,3 including in the mass media, and some scientists stated publicly
that they would consider taking up smoking if they had a family history of
dementia.

Tobacco companies began to sponsor conferences on dementia, perhaps because
it seemed to offer them a lifeline in an otherwise relentless sequence of
findings about the deleterious effects of smoking. If smoking reduced life
expectancy and also reduced the likelihood of survivors developing dementia
then, from a policy perspective, there might be a role for the habit in
later life.

The potential protective effects have some biological plausibility.
Alzheimer's disease affects neurotransmitter systems, particularly the
cholinergic system. Nicotine is a cholinergic agonist. The effect of
nicotine on cognition, attention, and reaction time has been studied in
non-cognitively impaired individuals, and nicotine is under investigation
as a therapeutic agent in several disorders.4 A drug that acts on nicotinic
receptors in the brain has just received regulatory approval in Sweden, the
first such drug to be approved in the European Union. These effects are
likely to be short term, with no obvious mechanism for long term effects.
Moreover, smoking's effect on risk for vascular disease, including
cerebrovascular disease,5 makes it a likely risk factor for vascular
dementia over the longer term.6

The effects of smoking on dementia clearly need investigating in relatively
unbiased populations and in longitudinal studies of reasonable duration in
which the risk factors are examined before the onset of any dementia. In
reporting one such study of British doctors in this week's BMJ (p 1097),
Doll et al also discuss the earlier case-control studies of risk for
Alzheimer's disease, highlighting the deficiencies of this approach for
dementia.7 In order to take part in a case-control study, patients need to
have survived. For Alzheimer's disease the diagnostic criteria demand
exclusion of those with vascular disorders, thus excluding those more
likely to have smoked in earlier life. These are among the many reasons why
the early case-control studies might have found a spurious "protective
effect." Although these limitations were discussed in most of the papers
reporting an apparent protective effect and in commentaries,8 the
reservations did not appear in all the media reports.

Currently a series of longitudinal studies of cognitive decline and
dementia is under way in Europe. The EURODEM group has reported the first
combined results of a group of European incidence studies in which people
aged 65 and over were followed for dementia over two to three years, having
answered questions on smoking at baseline.8 Doll et al review the findings
from a selection of these studies,7 which provide no evidence of a
protective effect and, if anything, suggest an increased risk.9 In a
further longitudinal study from Sweden cross sectional analysis showed the
apparent protective effect of smoking, but continued follow up revealed an
increased risk of subsequent dementia in smokers.10 These provide evidence
about risk over a short period of observation. The strength of the study
reported in this week's issue is its much longer time frame.

Over the years the study of British doctors has provided crucial evidence
on the wide ranging effects of smoking. The cohort has now reached the age
at which the investigators can look at the impact of smoking in mid-life on
mortality from dementia. The study was not designed to measure dementia as
an outcome, and its measurement of dementia is relatively weak, as
documentation of dementia on death certificates is known to be incomplete
and usually mentioned only in moderate to severe cases. Diagnosis of
subtypes of dementia is notoriously difficult during life. These
limitations are unlikely, however, to have introduced systematic bias. The
findings reported by Doll et al provide no evidence of a significant
protective effect in men.

This study cannot provide the detail necessary to answer questions about
the short term therapeutic effects of nicotine, its effects on minimal
dementia and cognitive decline, gene-environment interaction, or gender
specific effects. However, its findings are an important counterbalance to
the potentially biased earlier studies. As Doll et al point out, these
findings will be followed by many other longitudinal studies that should
clarify the relation between smoking at various stages of life and
subsequent dementia as most cohort studies now include some measures of
cognition.

In the meantime, taking both the European cohort findings and the British
doctors study together, the public health message is clear: at the
population level there is no protective effect of smoking in dementia.


by Carol Brayne
BMJ 2000;320:1087-1088
http://bmj.com/cgi/content/full/320/7242/1087

janet paterson
53 now / 41 dx / 37 onset
a new voice: http://www.geocities.com/janet313/
613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0