Smoking linked to Alzheimer's risk

“Heavy smoking in mid-life more than doubles the risk of developing Alzheimer's disease,” reports The Independent. It said that these findings come from a study in more than 21,000 middle-aged men and women in the US, who were followed for an average of 23 years.
 
This study looked at data on people’s smoking at age 50 to 60, then followed them to see who developed dementia (either Alzheimer’s disease or vascular dementia). It found that people who smoked more than two packs of cigarettes a day were more than twice as likely to develop dementia as people who never smoked. The study’s strengths include its large size, and the fact that it enrolled people in middle age and followed them up over a long period of time. It does have some limitations: mainly that it had to rely on medical records to identify people with dementia, which means that some people with dementia may have been missed.

Ideally, these results should be confirmed in further studies. However, smoking is already known to increase the risk of vascular disease, and so an association between vascular dementia and smoking seems plausible. The observed associations with Alzheimer’s disease could point towards a possible link between smoking and neurological disease as well.

Where did the story come from?

The study was carried out by researchers from the University of Eastern Finland and other research centres in Finland, Sweden and the US. It was funded by Kuopio University Hospital, the Juho Vainio Foundation, Maire Taponen Foundation, Kaiser Permanente, and the National Institute of Health and Academy of Finland. The study was published in the peer-reviewed journal _Archives of Internal Medicine.
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Many news sources reported this study and generally covered this story in an accurate and balanced way.

What kind of research was this?

This study investigated whether there is a link between smoking in middle age and the risk of dementia in later life. Although there is an established link between smoking and diseases such as lung cancer and cardiovascular disease, its effect on the risk of neurological conditions such as Alzheimer’s disease is less clear. Some existing studies have caused controversy by suggesting that smoking may reduce the risk of cognitive impairment. The researchers claim this is the first study to look at the long-term effects of mid-life smoking on the risk of dementia in older age in a large multi-ethnic group of people.

This was a prospective cohort study, which is the most appropriate way of investigating the possibility of a link between smoking and dementia. The participants were asked about their smoking habits at the start of the study, and followed over time to see if they developed dementia. This means that their answers should be free of the inaccuracies that may have been present if they had been asked to recall their smoking habits from as far back as two decades ago.

Also, as the brain changes associated with dementia begin a long time before symptoms appear, it is important to assess any risk factors before these changes start to occur. By assessing smoking in middle age, the researchers can be relatively certain that smoking habits preceded the onset of dementia and could be affecting the risk of developing the disease.

What did the research involve?

The researchers assessed the smoking habits of 20,000 adults aged between 50 and 60 in California. They followed them up over time to see which people developed dementia. They then carried out analyses to determine whether mid-life smoking affected a person’s risk of developing dementia.

The researchers used data collected as part of a study called the Multiphasic Health Checkup (MHC), run by the Kaiser Permanente healthcare organisation in the US. This study collected health and lifestyle information on more than 30,000 members of the Kaiser Permanente healthcare programme in 1978 to 1985, when they were aged 50 to 60. The current study included the 21,123 people who had provided information on their mid-life smoking and were still alive and enrolled with Kaiser Permanente in 1994. The researchers identified people with dementia by searching in healthcare records for dementia diagnoses made by doctors between 1994 and 2008. They were primarily interested in the two main types of dementia: Alzheimer’s disease and vascular dementia.

In their analyses, the researchers compared the risk of developing dementia among current and former smokers with that of people who never smoked. Current smokers were also grouped according to how much they smoked. Other factors that could have affected the results were taken into account, such as age, gender, education, race, marital status, body mass index, health conditions (such as diabetes, high blood pressure, high blood lipids, heart disease, stroke) and alcohol use in mid life.

What were the basic results?

During the 23 years of follow-up, about a quarter of participants (5,367 people) developed dementia. This included 1,136 people who developed Alzheimer’s disease, and 416 people who developed vascular dementia. The remainder were recorded only as “general dementia”.

The researchers worked out the number of cases of dementia for the different groups (never smoked, current smokers and former smokers) and how many ‘person years’ of follow-up each group had. They then calculated the risk of developing dementia in each group for every 10,000 person years of follow-up.

Among those who never smoked, about 409 people developed dementia in every 10,000 person years of follow-up. Among former smokers, this figure was 403 people per 10,000 person years. In current smokers it ranged from 398 in people smoking less than half a pack a day, to 786 people per 10,000 person years for people smoking two packs a day or more.

After taking into account factors that could affect the results, people who smoked more than two packs of cigarettes a day in mid life were more than twice as likely to develop dementia during follow-up as people who never smoked (hazard ratio [HR] 2.14, 95% confidence intervals [CI] 1.65 to 2.78). People who smoked one to two packs, or between half a pack and a pack of cigarettes a day, also had a higher risk of developing dementia (HR 1.44 and 1.37 respectively). People who smoked less than half a pack of cigarettes a day, or who were former smokers, were not more likely to develop dementia.

When looking specifically at Alzheimer’s and vascular dementia, people who smoked more than two packs of cigarettes a day in mid life were about 2.5 to 2.7 times more likely to develop these diagnoses during follow-up as people who never smoked (Alzheimer’s disease: HR 2.57, 95% CI 1.63 to 4.03; vascular dementia HR 2.72, 95% CI 1.20 to 6.18).

How did the researchers interpret the results?

The researchers concluded, “heavy smoking in midlife was associated with a greater than 100% increase in risk of dementia, [Alzheimer’s disease], and [vascular dementia] more than two decades later”. They say that these results suggest “that the brain is not immune to long-term consequences of heavy smoking”.

Conclusion

This large study suggests that heavy smoking around the age of 50 to 60 may increase the risk of dementia in later life. The prospective nature of this study and its size are strengths, but there are some limitations:

• The study had to rely on medical records to identify people with dementia. Some cases may have been missed or misrecorded. In particular, Alzheimer’s disease is difficult to diagnose, and a diagnosis is usually based on characteristic clinical and brain imaging findings and the exclusion of other possible causes. It can only be confirmed on post-mortem examination of the brain, which may not have been carried out on all the participants.
• Smoking was only assessed by self-report at the start of the study. People may not have been honest about their smoking, and this could potentially affect results. However, it would seem likely that people would under-report their smoking habits, and this would probably reduce rather than increase any link seen between smoking and dementia. In addition, the participants' smoking habits may have changed over follow-up, which could potentially affect results.
• The study took into account a number of factors that could affect the results, which increases the confidence that the findings demonstrate a true effect of smoking. However, it is still possible that unknown or unmeasured factors (for example, a person’s genetic makeup) could be responsible for or contribute to this link.

Ideally, the findings of this study should be confirmed by other long-term studies before any firm conclusions are drawn. However, smoking is already known to increase the risk of lung and cardiovascular disease. An association between vascular dementia (often the result of a stroke) and smoking would be plausible as smoking is known to increase the risk of vascular disease. However, the observed associations between dementia in general and Alzheimer’s disease could point towards a possible link between smoking and neurological disease as well.