Description
LO1. Understand key concepts and methods of epidemiology. LO2. Calculate and interpret basic epidemiology measures LO3. Draw appropriate inferences from epidemiologic data. LO4. Evaluate the strengths and weaknesses of data from epidemiologic studies. LO5. Apply evidence from epidemiologic investigations to public health policy and practice Assessment 2 – Examples of questions related to exam paper How do you think, why this study was necessary to conduct? What was the study design? How do you think if selected study design was appropriate for particular study? What was the research question of the study? What was the main exposure and outcome? What is the variables/variables of the study?Summary
Background Previous studies suggested a protective
effect of smoking on Alzheimer’s disease, but most were
case-control studies based on prevalent cases. The
findings of prospective studies on the association between
smoking and the risk of dementia are inconclusive.
Methods We did a population-based follow-up study of
elderly people who were initially free of dementia. 6870
people aged 55 years and older agreed to take part.
Smoking history was taken at baseline and participants
were classified as never smokers, former smokers, and
current smokers. During follow-up, we recorded all incident
cases of dementia. We used never smokers as the
reference category to calculate relative risks of dementia
and Alzheimer’s disease by Cox proportional hazards
regression, after adjustment for age, sex, education, and
alcohol intake. We also examined modification of risk by
age, sex, and the apolipoprotein E (APOE) genotype.
Findings During mean follow-up of 2·1 (range 1·5–3·4)
years, 146 incident cases of dementia were detected, of
which 105 were Alzheimer’s disease. Compared with never
smokers, smokers had an increased risk of dementia
(relative risk 2·2 [95% CI 1·3–3·6]) and Alzheimer’s
disease (2·3 [1·3–4·1]). Smoking was a strong risk factor
for Alzheimer’s disease in individuals without the APOE4
allele (4·6 [1·5–14·2]), but had no effect in participants
with this allele (0·6 [0·1–4·8]).
Interpretation Smoking was associated with a doubling of
the risk of dementia and Alzheimer’s disease. Our finding
that carriers of the APOE4 had no increased risk of
dementia suggests an interaction between smoking and
the APOE4 genotype in the aetiology of Alzheimer’s
disease.
Lancet 1998; 351: 1840–43
Introduction
The prevalence of dementia increases greatly with age: at
least 30% of people aged 85 years and older have the
disorder.1 Alzheimer’s disease and vascular dementia are
the main subtypes of dementia, and account for about
90% of affected patients.1 Smoking is a risk factor for
vascular disease, including atherosclerosis and
thrombosis, and increases the risk of vascular dementia.2,3
Reduction of cerebral perfusion is an acute effect of
cigarette smoking and may be harmful in elderly people
with a compromised cerebral circulation.4 Vascular
involvement is probably more important than previously
thought in the pathogenesis of Alzheimer’s disease.5–7
Nonetheless, an inverse association has been reported
between smoking and Alzheimer’s disease.8Van Duijn and
colleagues9 showed that in early-onset Alzheimer’s
disease, the possible protective effect of smoking was
limited to carriers of the apolipoprotein 4 (APOE4)
allele. Although there are several possible explanations for
a protective effect of smoking on Alzheimer’s disease,8,9
this finding in previous studies could reflect bias.10
Smoking also strongly increases risk of premature death,
and those smokers who survive to old age may be a more
selected group than non-smokers of similar age.11
In this prospective population-based study we
examined the association of cigarette smoking with
dementia and Alzheimer’s disease, and whether this
relation depended on age, sex, and the APOE genotype.
Methods
Study design and population
The Rotterdam Study is a community-based prospective cohort
study of individuals aged 55 years and older,12 which was
undertaken with the approval of the local medical ethics
committee. All 10 275 residents of a Rotterdam suburb who
were older than 55 years were eligible. 7983 (78%) residents
agreed to take part and gave their informed consent and
permission for us to obtain medical information from their
family doctor and medical specialists. Baseline examinations took
place between 1990 and 1993 and comprised a home interview
and medical examinations at the study centre or at their
institution for those living in residential homes. At baseline we
assessed 7528 (94%) individuals for dementia,1 474 of whom
were diagnosed with the disorder and excluded from the study.
Of the 7054 without dementia, 184 were excluded because of
missing data on smoking history. The 6870 participants were
followed-up for about 2 years, until the second round of
examinations. For individuals who were not examined in person,
follow-up was completed by assessment of their medical files.
Dementia diagnosis and assessment
For the assessment of dementia, the same protocol was used at
baseline and at follow-up which we have described in more detail
elsewhere.13 Briefly, all participants were screened with a brief
test of cognition (mini mental state examination14 and the
geriatric mental state schedule, organic level15); those with
positive results underwent further cognitive testing, and a carer
or friend was interviewed about the daily funtioning of the
ARTICLES
1840 THE LANCET • Vol 351 • June 20, 1998
Departments of Epidemiology & Biostatistics (A Ott PhD,
A J C Slooter MD, Prof A Hofman PhD, J C M Witteman PhD,
C M van Duijn PhD, M M B Breteler PhD) and Neurology
(F van Harskamp MD), Erasmus University Medical School, PO Box
1738, 3000 DR Rotterdam, Netherlands; and Neurogenetics
Laboratory, Flanders Interuniversity Institute for Biotechnology,
Born-Bunge Foundation, Department of Biochemistry, University
of Antwerp, Antwerp, Belgium (Prof C Van Broeckhoven PhD)
Correspondence to: Dr M M B Breteler
(e-mail: breteler@epib.fgg.eur.nl)
Smoking
