Smokers More Likely to Develop Dementia, Alzheimer's Disease

September 10, 2007 — Individuals who smoke are more likely to develop Alzheimer's disease (AD) or dementia than nonsmokers or those who smoked in the past, a study suggests.
The Rotterdam Study, a large population-based, prospective cohort study from the Netherlands showed individuals aged 55 years or older who were current smokers were 50% more likely to develop dementia than those who had never smoked or were past smokers.
"Smoking increases the risk of cerebrovascular disease, which is also tied to dementia. Another mechanism could be through oxidative stress, which can damage cells in the blood vessels and lead to hardening of the arteries. Smokers experience greater oxidative stress than nonsmokers and increased oxidative stress is also seen in Alzheimer's disease," principal investigator Monique M. Breteler, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, said in a statement from the American Academy of Neurology.
The study is published in the September 4 issue of Neurology.
Previous Research Fell Short
According to the authors, previous studies examining smoking and the risk for dementia have been largely observational and limited by short follow-up, long intervals between baseline and follow-up assessments, and unspecific determination of dementia diagnosis.
Whereas the Rotterdam Study previously reported an increased risk for dementia and AD in current smokers without the apolipoprotein E (APOE) ε4 allele at 2-year follow-up, the objective of the present study was to reassess this association after longer study duration and with more incident dementia cases.
Investigators looked at smoking habits and pack-years of smoking to determine their association with the risk for dementia, AD, and vascular dementia (VaD).
The study included 6868 participants aged 55 years or older who were free of dementia at study outset. Baseline interviews were conducted between 1990 and 1992. All participants were interviewed in their homes about current and past health, medication, lifestyle, and risk factors for chronic disease. All study participants were asked about past and current smoking habits.
At baseline and all follow-up examinations, a 3-stage protocol was used to screen all participants' cognition using the Mini-Mental State Examination (MMSE) and the Geriatric Mental State schedule (GMS) organic level.
Subjects who scored lower than 26 on the MMSE or higher than 0 on the GMS organic level underwent the Cambridge Examination of Mental Disorders in the Elderly.
Individuals suspected of having dementia underwent examination by a neurologist and neuropsychologist and, if possible, also underwent a magnetic resonance imaging brain scan.
In addition, the entire study group was continuously monitored for incident dementia through computerized linkage between the study database and computerized medical records from general practices and the Regional Institute for Outpatient Mental Health Care.
Participants were also assessed for the presence of the APOEε4 allele.
No Association With Past Smoking
Of the 6868 individuals without dementia at baseline, 706 (10.3%) were diagnosed with dementia at 7-year follow-up. Of these subjects, 555 (78.6%) had AD and 79 (11.2%) had VaD.
After adjusting for age, sex, alcohol intake, education, and intake of antioxidants, current smoking was associated with a higher risk for incident dementia and AD compared with never smoking.
However, when the analyses only included VaD as the outcome, there was no association between smoking status and risk for VaD. Furthermore, there was no association between past smoking and the risk for dementia, AD, or VaD.
In addition, current smoking was not related to an increased risk for dementia, AD, or VaD among individuals with the APOEε4 allele. However, individuals without the gene had a significantly increased risk for dementia and AD.
"We found an association between current smoking at baseline and an increased risk of dementia and AD that was restricted to persons without the APOEε4 allele. There was no association between current smoking and risk of VaD, and there was no association between past smoking and risk of dementia, AD, or VaD," they write.
These findings confirm those of the investigators' earlier study that found an increased risk for dementia and AD in persons without the APOEε4 allele at 2-year follow-up.
According to the authors, there are several potential explanations for this finding. Among them is the hypothesis that APOEε4 carriers may have an increased risk for AD such that other risk factors do not further increase risk.
The lack of association may also result as follows: in APOEε4 carriers smoking may be harmful through vascular mechanisms but also potentially beneficial.
"This hypothesis is supported by previous findings that persons with AD who are APOEε4 carriers have fewer nicotinic receptor binding sites and lower activity of choline acetyltransferase than noncarriers. Smoking could counterbalance the APOEε4 associated impairment by facilitating the release of acetylcholine or increasing the density of nicotinic receptors," they write.
The authors have disclosed no relevant financial relationships.
Neurology. 2007;69:998-1005.