Cardiovascular Disease and Smoking Affect Memory Performance

Smoking is associated with worsened verbal learning and memory performance more in women than in men.

Cardiovascular Disease and Smoking Affect Memory Performance, MindCrowd study, May 2021.

Cardiovascular Disease Risk Factors and Dementia

Vascular contributions to cognitive impairment and dementia (VCID) include blood vessel injuries. These can cause significant changes to memory, thinking and behavior.

Problems in the circulatory system are also linked to increased risk of Alzheimer’s disease, the 6th leading cause of death in the US.

Vascular-related dementia is the second most common cause of cognitive decline. Alzheimer’s-related dementia is the first most common cause of cognitive impairment as we age.

Risk factors for cardiovascular disease correlate with increased risk of dementia in older age. Tobacco smoking is one of these risk factors.

Is Smoking Linked to Dementia?

Early reports suggested that smoking tobacco might improve cognition and reduce the risk of dementia.

More recent evidence shows that active smoking has neurotoxic effects on the brain. It also suggests that smoking doubles the risk of dementia for older adults.

Smoking causes vascular damage and increased systolic blood pressure. Both contribute to the risk of stroke.

Tobacco smoking may increase the risks associated with underlying vascular  disease. Thus, increasing the risk of memory and thinking impairment.

Smoking with hypertension is one of the greatest risk factors for heart attack and stroke.

Tobacco smoking is also a major risk factor for cardiovascular disease and chronic obstructive pulmonary disease (COPD). Both of which can decrease cognitive function. Furthermore, the prevalence rates of dementia may be greater in women than men.

A recent study of middle-aged Hispanics showed that women with vascular issues had more memory and thinking problems than men.

Yet, it is currently unknown if the effects of smoking on verbal learning and memory function are different between men and women.

Several studies have found an association between smoking, cognitive decline, and dementia.

But the majority of these studies did not assess biological sex as a main variable of interest. Thus, this difference was not explored.

And the question of whether there are differences in how smoking affects cognition in men and women remains unresolved.

Does Smoking Affect Memory Performance of Men and Women Differently?

How might we explain why so few studies have tested women and men separately? Because there is a need for a large group of participants to conduct valid statistical analyses to detect these interactions.

The few studies that did, had a small number of participants and have found contradicting results. Some studies suggest no sex effect. Some suggest that smoking may affect men’s cognition more strongly than women’s. And other studies have found a larger effect of smoking on memory and thinking skills in women.

It seems that smoking often impacts women’s risk more for diseases that happen outside of the central nervous system.

An analysis of 2.4+ million people says that women who smoke have a 25% greater risk of atherosclerosis than men who smoke, compared with nonsmokers and independent of other cardiovascular risk factors.

Women smokers may also have a greater relative risk of lung cancer than men who smoke. Other studies have found the effects of smoking on bone density and Crohn’s disease are different between men and women.

Human and animal studies point to many sex differences in the way nicotine binds to brain receptors.

So, we should look into sex-specific effects when we study the relationship between smoking and cognition.

MindCrowd Study: Cardiovascular Disease and Smoking Affect Memory Performance

First, we set out to discover if biological sex made a difference on smoking and memory performance in healthy adults. (18–85 years old)

Then, we estimated how many participants we would need to detect this interaction. Our analyses suggest that we would need at least 10,000 people to notice a significant sex by smoking interaction at least 50% of the time. There is a possibility that previous studies may have been underpowered to find the interaction.

The harmful effects of smoking on the cardiovascular system are well known. There is also an association between cardiovascular disease and cognitive impairment and dementia.

And we wanted to know if the influence on memory performance of diabetes, heart disease, hypertension, and stroke history combined was different for each sex.

Would smoking and a cardiovascular disease combined have a bigger negative impact on learning for women when compared to men?

We used MindCrowd’s memory and demographic data of more than 70,000 persons aged 18 to 85. To date, this is the single broadest age-range study of the relationship between smoking, cardiovascular disease and verbal memory.

Few studies have assessed the effects of cardiovascular disease in younger adults before. It’s important to understand this relationship to devise possible treatments and interventions.

MindCrowd’s Findings: Smoking Impact on Memory by Sex

Our research revealed a more significant impact of smoking on women’s word-pair association memory than on men’s.

Thus, smoking impairs women’s learning and memory more than it does men.

Previous efforts to measure cognitive  capacity in men and women smokers produced mixed results. We believe the reason is the limited number of participants in those studies. By analyzing MindCrowd’s data, this study produced results that show definitive trends.

According to Matt Huentelman, Ph.D., TGen Professor of Neurogenomics, a MindCrowd founder and the study’s senior author:

• These results suggest that smoking and cardiovascular disease impact verbal learning and memory throughout adulthood, starting as early as age 18.
• Smoking is associated with decreased learning and memory function in women.
• Other cardiovascular diseases are associated with greater decreased learning and memory function in men.

Cardiovascular Disease and Smoking Analysis: Impact on Learning and Memory

Besides Alzheimer’s, the most important cause of cognitive decline is known as “vascular contributions to cognitive impairment and dementia” or VCID. VCIDs arise from stroke and other vascular brain injuries. These injuries cause significant changes to memory, thinking and behavior. Smoking and cardiovascular disease make VCIDs worse.

“Our findings highlight the importance of considering biological sex in studying vascular contributions to cognitive impairment and dementia.”

Candace Lewis, Ph.D., a postdoctoral fellow in Dr. Huentelman’s lab, and the study’s lead author.

Cigarette smoking and cardiovascular disease in adults as young as 18 may worsen memory performance.

Furthermore, we found that the impact of smoking on verbal recall was worse in women. Whereas the impact of cardiovascular disease on memory performance was worse in men.

“This study’s findings are important,” Dr. Lewis said. According to the U.S. Department of Health and Human Services, cigarette smoking is the nation’s leading cause of preventable disease and death. It accounts for nearly 1 in 5 deaths. And cardiovascular disease is the leading cause of disease and death worldwide, and a key predictor of cognitive decline and VCID.

Women are negatively affected to a larger degree than men when it comes to smoking and verbal recall.

A 2018 report showed that in the United States:

• 15.6% of men were smokers
• 12.0% of women were smokers

Thus, men were more likely to be current cigarette smokers than women. We replicated this finding within our MindCrowd study. 

On average, women smoke fewer cigarettes per day and have lower levels of cotinine in saliva, compared with men. Cotinine is found in tobacco and is used to measure exposure to tobacco smoke.

In the US, smoking rates for women have increased relative to smoking rates for men. The popularity of smoking among women in low to middle-income countries may be increasing.

This is very interesting, since there are more Alzheimer’s cases in women than men. These data suggest that smoking could potentially speed up these trends.

Men may be at a slightly higher risk for VCID throughout most of their lives. But, some risk factors for VCID, such as preeclampsia, menopause and hormone replacement, primarily affect women.

While the risk of dementia increases with age, decreases in certain memory and thinking abilities happen all through life. Others, like vocabulary ability increase with age.

It is important to understand how modifiable habits, like smoking, affect our cognition.

Effects of Smoking on Memory Performance: Nicotine, Vaping and other Additives

The MindCrowd study analyzed sex differences in smoking behaviors. But biological sex differences could also explain why smoking impacts women’s cognition more.

Animal studies have shown that female rats have a higher response to nicotine in their brain receptors than male rats. Whether they are exposed to it or not.

This response to nicotine influences several cognitive functions and neurotransmitters. Thus, higher response in women could worsen the effects of smoking on verbal learning.

It is not clear whether smoking-related changes in learning and memory are due to:

• nicotine exposure or
• the complex chemical makeup of cigarette tobacco and its additives.

This is an important distinction, as adult usage of e-cigarettes/vaping increased from 2.8% in 2017 to 3.2% in 2018.

But MindCrowd did not ask about vaping. So, more research is needed to observe the relationship between e-cigarette use and memory performance. E-cigarette and tobacco have a different mix of chemicals. Thus, it is possible that the effects of their use will differ.

Cardiovascular Disease and Memory Performance Differences by Sex

There is an established relationship between smoking and cardiovascular disease. So, we tested the impact of cardiovascular disease on memory performance in women and men.

Much of the prior research in this domain has focused on cardiovascular risk scores. We used number of cardiovascular disease incidents, as opposed to risk factors.

We found cardiovascular disease is a larger risk factor for cognitive decline in men.

It is unclear why we found larger effects in men, but, it could be due to the broad age range included in our study. Generally, this relationship is studied in older adults. There are a few examples that include 35+, and one study of 18–30 year olds.

The study of this relationship in younger people will allow us to identify treatments and interventions.

The Importance of the MindCrowd Study Findings

Sex moderates the relationship between smoking status and verbal learning and memory performance.

Smoking may impact women’s cognitive health to a greater degree than men.

A larger number of participants may be needed to produce more reliable results.

It is important to include sex as a variable in studies. It can help identify influential factors on learning and memory performance across development and aging.

According to Brian Tiep, M.D., City of Hope Director of Pulmonary Rehabilitation and Smoking Cessation:

• This study points out some unpredicted but important differences between the sexes relating to cognitive decline.
• The impact on mental acuity seems progressive over time — some more rapid than others.
• Living habits related to diet, exercise and smoking  are consequential and may be different between men and women.

“This study supports the importance of maintaining cardiovascular health and quitting smoking, not only for cancer care and prevention, but to improve brain function,” Dr. Tiep added.

Limitations and Advantages of the Online MindCrowd Study

The MindCrowd study is large, widely available, and online. We rely on self-reported answers to questions about demographic, lifestyle and health.

When people enter their height and weight online, they tend to be from 0.3 to 20% different from the in-person data.

The pressure to “look good” in front of an investigator is less of an issue when using online assessments. Thus, socially unacceptable behavior like smoking, may be more accurate online than offline.

We went even further to identify the potential role that false-reporting may play on our smoking effect. We added error ourselves and re-analyzed the effect of smoking. This was repeated a total of 10,000 times for each error percentage!

Conclusion: it is unlikely that smoking self-reporting errors are driving our results.

This study has some limitations

First, the smoking rate in MindCrowd is lower than national averages. This may happen because healthier people tend to take part in observational research. We used propensity matching to confirm the sex effect. This statistical technique suggests our results do apply to the broader population.

Next, the primary outcome measure was based on a single verbal memory and learning test. If we used a measure with a more comprehensive score range we may have tracked subtle differences between ages. Thus, our results may not be generalizable to different cognitive functions.

Our study participants self-report on smoking and cardiovascular disease. We did not attempt to verify these with the participants’ medical records.

Previous studies have suggested that more women under-report smoking than do men.

A higher percentage of false self-reporting smoking status by women would have weakened our results. So, the study’s results may underestimate the difference between men and women who smoke.

Additionally, we only asked for smoking status. We did not ask for their smoking history or number of cigarettes smoked a day.

Finally, the cross-sectional design of this study does not allow a causal conclusion. There may be other factors driving this association which were not measured . Factors like social class, diet, etc.

A longitudinal study should follow to verify our results. Longitudinal studies look at variables over an extended period of time.

Despite these limitations, there are several advantages of using a large online study.

People who participated in the MindCrowd research, include a wide range of adults 18 to 85 years old. We were able to assess the link between CVD, smoking and memory performance in the broadest single study age range used to date.

The MindCrowd scientific study assessed a considerable number of variables. This is how we could control for many potential confounding variables. Conducting propensity matching was possible due to the large sample size.

Our analyses show that the effect of smoking on memory performance is robust in women, over and above other health factors.

Propensity score matching helped isolate the effect of smoking on memory performance.

There is another advantage of using an online study design. You can use an identical study as opposed to trying to harmonize data across sites. The latter is often required when combining smaller, local cohorts.

Furthermore, MindCrowd research participants are geographically diverse. They live in both rural and urban settings. This allows a higher degree of generalizability.

About the Cardiovascular Disease and Smoking Affect Memory Performance Study

The “Smoking is associated with impaired verbal learning and memory performance in women more than men” study received support from:

• the Mueller Family Charitable Trust;
• the Arizona Department of Health Services through the Arizona Alzheimer’s Consortium;
• Flinn Foundation;
• the McKnight Brain Research Foundation;
• a grant from the National Institute on Aging;
• the TGen Foundation led philanthropic efforts to support MindCrowd.

Other contributors to this study included:

• the Arizona Alzheimer’s Consortium;
• the Norwegian University of Science and Technology;
• the Evelyn F. McKnight Brain Institute at the University of Miami;
• the Miami Clinical and Translational Science Institute;
• the University of Arizona.

MindCrowd is an internet-based study of how the human brain changes with age. Over 225,000 participants have joined the study since its inception in 2013. It is open to all individuals who are 18 years of age and older. The test is available in both English and Spanish.