Heavy Smoking in Midlife Doubles the Risk for Alzheimer's Disease

Fran Lowry

October 28, 2010

October 28, 2010 — Heavy smoking in midlife more than doubles the risk of developing Alzheimer's disease (AD) and other forms of dementia 2 decades later, according to a new observational study reported online October 25 in the Archives of Internal Medicine.

The finding, from a large cohort of more than 20,000 people, suggests that the brain is not immune to long-term consequences of heavy smoking.

"This study shows that if you are an elderly person and you've been smoking and you are lucky enough that you didn't get respiratory disease or cancer or cardiovascular disease, you're still at risk for another disease that's pretty devastating that can occur in late life," senior study author Rachel Whitmer, PhD, an epidemiologist at Kaiser Permanente Division of Research, Oakland, California, told Medscape Medical News.

Some studies suggest that smokers have a reduced risk for Parkinson's disease and other neurodegenerative conditions, as well as cognitive impairment, but others have found an association between smoking in midlife and later development of AD and other dementias.

Benefit to Quitting

In this study, which was led by Minna Rusanen, MD, from the University of Eastern Finland and Kuopio University Hospital, the researchers analyzed prospective data from the Kaiser Permanente Medical Care Program of Northern California, which gave them access to a large and ethnically diverse population, to further evaluate the risk.

The data comprised a cohort of 21,123 members who participated in a survey between 1978 and 1985, when they were 50 to 60 years old. Diagnoses of dementia, AD, and vascular dementia were tracked from January 1, 1994, when participants were an average of 71.6 years old, through July 31, 2008.

During an average of 23 years of follow-up, 5367 participants (25.4%) were diagnosed as having dementia. Of these, 1,136 were diagnosed as having AD and 416 as having vascular dementia.

The study showed that participants who smoked more than 2 packs per day in middle age had a more than 100% increased risk for dementia, AD, and vascular dementia, compared with those who said that they were never smokers.

After adjusting for age, sex, education, race, marital status, hypertension, hyperlipidemia, body mass index, diabetes, heart disease, stroke, and alcohol use, the hazard ratio for dementia was 2.14 (95% confidence interval [CI], 1.65 – 2.78); for AD, it was 2.57 (95% CI, 1.63 – 4.03), and for vascular dementia, it was 2.72 (95% CI, 1.20 – 6.18).

The study also showed that people who reported smoking 1 to 2 packs per day had a 44% greater risk for dementia, and people who reported half a pack to 1 pack per day had a 37% greater risk.

Individuals who had quit by the time they took the survey, however, did not have a greater risk compared with never smokers, Dr. Whitmer noted.

"That's an important message. It shows that there is definitely a benefit to quitting," she said.

Mechanism Unclear

"This is an observational study, and we can't say that smoking is causative. We don't know what the mechanisms are, but we can guess that certainly cerebral vascular disease has something to do with it. People who smoke have higher levels of inflammatory factors, and that is also associated with Alzheimer's disease and dementia, so there probably a number of different things going on," Dr. Whitmer said.

Having escaped the other diseases that are known to be associated with smoking, like lung cancer, emphysema, and heart disease, smokers might feel a false sense of invulnerability. It is important for them to know that they are not invulnerable, she added.

"This is the first study that looked over the long term. This is a very tricky question to look at because smokers are more likely to die and to not make it to an age where they would be at risk for dementia. This study is large enough that we had enough smokers who were still alive in 1994, when we started looking at the diagnoses of dementia. We had enough heavy smokers," she said.

Biased Studies

Medscape Medical News asked David Knopman, professor of neurology at the Mayo Clinic in Rochester, Minnesota, and spokesperson for the American Academy of Neurology, to comment on this study.

"It certainly confirms most of the recent literature that smoking is in fact a risk factor for dementia. The earlier studies that claimed that somehow smoking was protective were deeply biased, probably due to survival bias," he said.

"But because smoking is such an obvious risk factor for stroke and cerebral vascular disease, it was inconceivable that smoking wouldn't also be a risk factor for dementia."

The only problem with the study is that the diagnoses of dementia depended on primary care physicians' diagnoses, said Dr. Knopman, who is also deputy editor of Neurology.

"These were not research diagnoses, they were done by docs in the trenches, and one does have to question the ability of those folks to differentiate Alzheimer's dementia from vascular dementia.

"To the extent that even experts can't do that, I would rather view this data from the perspective of dementia generally. Had I been a reviewer or an editor, I would have made them downplay the distinctions between Alzheimer's and vascular dementia," he said.

Still, "whether it's Alzheimer's or it's just dementia in general, the bottom line is the same, that smoking promotes late life cognitive impairment. And that's bad," he added.

Dr. Whitmer and Dr. Knopman have disclosed no relevant financial relationships.

Arch Intern Med. Published online October 25, 2010.

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