CHICAGO – Smoking in midlife might increase the chance of Alzheimer's in later life among those who already carry an increased genetic risk.
A population-based Finnish study with more than 20 years of follow-up concluded that carriers of the apolipoprotein E4 allele who smoked in midlife were seven times more likely to develop Alzheimer's than were carriers who didn't smoke. Alcohol consumption seemed to exacerbate the smoking-associated risk; carriers who drank frequently and smoked at midlife were more than 11 times as likely to develop the disorder as were carriers who never indulged in either behavior, Dr. Minna Rusanen said at the International Conference on Alzheimer's Disease.
The news is actually good for apo E4 carriers, who are considered almost certain to develop the disorder at a relatively young age, she said in an interview. “Recent knowledge about the environmental risk factors of the disease is giving hope to genetically susceptible people,” said Dr. Rusanen of the Kuopio (Finland) University Hospital. “The risk of developing Alzheimer's may be lowered by adopting an overall healthy lifestyle early in life. Promoting smoking cessation should be one of the major issues in the public education; it could help to prevent, or at least delay, the onset of Alzheimer's, and thus help one to live a cognitively healthy life also through old age.”
The association between smoking and dementia has never been conclusively proved, Dr. Rusanen noted. “Several case-control studies in the 1980s and 1990s suggested an inverse relationship between smoking and dementia, but this was probably due to a survival bias.” Some studies found a positive association only among apo E4 noncarriers, but one concluded that apo E status didn't modify dementia risk among smokers. The connection between smoking and Alzheimer's risk, however, is biologically plausible. “Smoking is known to have negative vascular effects, and predispose to cerebrovascular disease by accelerating atherosclerosis and inducing oxidative stress and inflammation–mechanisms which are also thought to have relevance in the development of Alzheimer's.”
To further investigate this question, Dr. Rusanen and her colleagues extracted data from the Finnish Cardiovascular Risk Factors, Aging, and Dementia study. The study included 2,000 participants who had been examined during midlife in four separate samples (1972, 1977, 1982, and 1987). After an average follow-up of 21 years, 1,449 of these people took part in a reexamination held in 1998. At that time, subjects were aged 65–79 years; 61 had developed some type of dementia, with Alzheimer's accounting for 48 of those cases.
Information on smoking status was available for 1,419 subjects. Of these, 321 were smokers during midlife, 272 had smoked in their younger years, and 826 had never smoked.
After researchers controlled for socio-economic status, blood pressure, cholesterol, body mass index, heart disease, stroke, diabetes, and lung disease, there was no association between smoking and Alzheimer's disease in any group except apo E4 carriers. Carriers who smoked at midlife were almost seven times more likely to have developed the disorder than were the nonsmoking carriers.
The risk increased again when Dr. Rusanen factored in alcohol consumption at midlife. Again, apo E4 carriers fared significantly worse than any other group. Midlife smokers who drank either occasionally or frequently were 11 times more likely to develop Alzheimer's than were carriers who abstained from both behaviors.
Dr. Rusanen noted that her study differs slightly from other cohort studies in its timing. “The smoking habits of the subjects were investigated in midlife, [about] 21 years prior to the reexamination, which means that we can really examine smoking as a predisposing factor for dementia.”
Another matter that should be considered is that “the effect of apo E on dementia risk is believed to attenuate with increasing age. Our cohort is quite young, with a mean age of the participants at midlife of 50 years, so it is likely that the effect of apo E is more easily seen in our cohort than in a cohort with older persons,” Dr. Rusanen said at the meeting, which was sponsored by the Alzheimer's Association.