How is smoking linked to Alzheimer’s disease and other dementias?

Science and Health

Besides all the disorders caused by smoking – cancer, heart disease, lung diseases, diabetes, and chronic obstructive pulmonary disease (emphysema and chronic bronchitis) and more – it has now been found to shrink the brain, raising the risk of premature dementias like Alzheimer’s disease (AD). 

It has been known for some time that there are connections between smoking behavior and lower total brain volume and gray and white matter volumes. Now, researchers at the Washington University School of Medicine in St. Louis offer some good news – that kicking the habit prevents further loss of brain tissue – but stopping smoking still fails to restore the brain to its original size. Since people’s brains naturally lose volume with age, smoking effectively causes the brain to age prematurely, the researchers said.

The findings, published in Biological Psychiatry: Global Open Science under the title “Investigating the Relationship Between Smoking Behavior and Global Brain Volume,” help explain why smokers are at high risk of age-related cognitive decline and AD.

“Up until recently, scientists have overlooked the effects of smoking on the brain, in part because we were focused on all the terrible effects of smoking on the lungs and the heart,” said senior author psychiatrist Dr. Laura Bierut. “But as we’ve started looking at the brain more closely, it’s become apparent that smoking is also really bad for your brain.”

CIGARETTES ON display at a convenience store in Safed carry warnings that smoking causes cancer, heart disease, stroke and other harm to smokers and their children. (credit: David Cohen/Flash90)

The relationship between smoking and brain health

Scientists have long known that smoking and smaller brain volume are connected, but they’ve never been sure which triggers what. And there is a third factor to consider – genetics, as both brain size and smoking behavior are heritable. About half of a person’s risk of smoking can be attributed to his or her genes.

To disentangle the relationship between genes, brains and behavior, Bierut and graduate student Yoonhoo Chang, who was the first author, analyzed data drawn from the UK Biobank, a publicly available biomedical database that contains genetic, health and behavioral information on half a million people, mostly of European descent. A subset of over 40,000 UK Biobank participants underwent brain imaging that can be used to determine brain volume. The team analyzed data on brain volume, smoking history and genetic risk for smoking of 32,094 people.

Each pair of factors proved to be linked – a history of smoking and brain volume; genetic risk for smoking and history of smoking; and genetic risk for smoking and brain volume. In addition, the connection between smoking and brain volume depended on dose; the more packs a person smoked per day, the smaller his or her brain volume.


When all three factors were considered together, the association between genetic risk for smoking and brain volume disappeared, while the link between each of those and smoking behaviors remained. Using a statistical approach known as mediation analysis, the researchers determined the sequence of events: genetic predisposition leads to smoking, which leads to decreased brain volume.

“It sounds bad, and it is bad,” Bierut said. “A reduction in brain volume is consistent with increased aging. This is important as our population gets older because aging and smoking are both risk factors for dementia.”

Unfortunately, the shrinkage seems to be irreversible. By analyzing data on people who had quit smoking years before, the researchers found that their brains remained permanently smaller than those of people who had never smoked. “You can’t undo the damage that has already been done, but you can avoid causing further damage,” Chang said. “Smoking is a modifiable risk factor. There’s one thing you can change to stop aging your brain and putting yourself at increased risk of dementia, and that’s to quit smoking.”