Heavy smokers show brain atrophy typical of Alzheimer's

A new study using MRI shows that smoking damages key areas of the brain involved in memory and thinking, and that being overweight may increase the damage, raising new questions about dementia prevention.

A recent study published in the journal NPJ Dementia examined the relationship between smoking and brain atrophy, and whether body mass index (BMI) moderated this relationship. The study found that smokers had significantly lower gray and white matter volumes in their brains than non-smokers. When BMI was included in statistical models, the association between packs per year smoked and brain volume loss was weakened, suggesting a possible mediating effect rather than direct causation.

Neurodegenerative disorders: prevalence and risk factors

A neurodegenerative disorder occurs when neurons in the brain and nervous system gradually lose function, leading to a decline in physical and cognitive abilities. Alzheimer's disease (AD) is the most common type of dementia, affecting memory, cognition, and behavior.

Dementia prevalence has been increasing worldwide. According to a recent study, about 47 million people worldwide have been diagnosed with dementia, and about 10 million new cases are expected to be added each year.

Numerous studies have identified risk factors for dementia in early, middle, and late life. Smoking is one factor, estimated to be involved in up to 14% of dementia cases worldwide. Toxins in cigarette smoke can cause neuroinflammation, a mechanism closely linked to AD. In addition to dementia, previous studies have also shown that smokers are at higher risk of developing cerebrovascular and respiratory diseases.

Although previous meta-analyses have linked smoking to an increased risk of dementia, few large studies have examined how smoking history and intensity are associated with MRI-measured brain atrophy, a biomarker of neurodegeneration. To assess this, it is necessary to examine the relationship between smoking and brain atrophy, which is the loss of brain tissue due to shrinkage or death of neurons with a reduction in the number of neural connections.

Researchers typically track brain atrophy in AD and other neurodegenerative disorders using neuroimaging and volumetric assessment using T1-weighted MRI — which is different from natural aging. MRI is used to assess brain volume loss, a biomarker of neurodegeneration.

Only a few large studies have examined the association between smoking and brain atrophy measured by MRI, which may play a key role in understanding the contribution of smoking to cognitive decline and AD.

About the study

The current study tested the hypothesis that individuals with a history of smoking experience greater brain atrophy at the whole-brain and lobe levels compared to non-smokers.

A total of 10,134 participants aged 18 to 97 years were recruited from four study sites. All participants underwent whole-body MRI without contrast. Before the scan, they completed questionnaires that collected information on their demographics, medical history, and smoking status. Each participant reported the number of packs per day they smoked and the number of years they had smoked.

Based on these questionnaires, participants were divided into groups: smokers (non-zero pack-years) and non-smokers (zero pack-years). Pack-years are an indicator of tobacco exposure that takes into account the duration and intensity of smoking. The smoker group included 3,292 people, and the non-smoker group included 6,842 people.

The study used FastSurfer, a proven deep learning pipeline, to quantify brain volume from 3D T1 images. A deep learning model was also used to segment intracranial volume (ICV).

A regression model was performed for smokers to analyze the relationship between pack-years and brain volumes:

• Model 1: adjusted for age, gender and study center;
• Model 2: with additional adjustment for BMI.

Research results

Compared with non-smokers, smokers were more likely to be female, Caucasian, have a higher BMI, be older, and have more type 2 diabetes and hypertension. The mean pack-years in the smoker group was 11.93.

Comparisons across regions showed lower brain volumes in the smoking group. Pearson bivariate analysis showed a moderate positive correlation between higher BMI and higher pack-years. Comparisons of models 1 and 2 showed a decrease in statistical significance and effect size in 11 brain regions when controlling for BMI, indicating a possible, but not proven, mediating role of BMI in the association between smoking and brain atrophy.

Importantly, even after accounting for BMI, smokers still had significant atrophy in several regions, including areas associated with Alzheimer's disease such as the hippocampus, posterior cingulate cortex, and precuneus.

Conclusions

The present study showed that individuals with a history of smoking and a higher number of pack-years had evidence of brain atrophy. Preliminary results also indicate that BMI may play a potential role in mediating the association between smoking and brain volume loss. Thus, obesity and smoking are two modifiable risk factors that may be used in the future to prevent dementia, including AD.

Further studies are needed in the future to examine the potential mediating effect of white matter hyperintensity volume and brain atrophy in the context of smoking history.

The key strengths of this study are the analysis of a large cohort with a history of smoking and quantitative structural brain imaging. In addition, it was possible to measure brain volume in regions affected by AD pathology, such as the hippocampus, posterior cingulate cortex, and precuneus.

Despite its strengths, the cross-sectional nature of the study limits the ability to draw causal conclusions. Also, the design did not include cognitive tests or AD biomarkers such as amyloid or tau, limiting the ability to directly link brain atrophy to dementia. Therefore, longitudinal studies are needed to confirm the role of BMI in this relationship.