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No Smoking, Heart Health Linked to Cognitive Health

Researchers have found both smoking and cardiovascular disease impair the ability to learn and memorize. Find out more.

In the largest study of the associations between smoking and cardiovascular disease on cognitive function, researchers at the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, found both impair the ability to learn and memorize; and that the effects of smoking are more pronounced among females, while males are more impaired by cardiovascular disease.

The findings were published in the journal Scientific Reports.

Previous attempts to quantify cognitive function among smokers and assess sex differences produced mixed results. The TGen researchers attribute this to the limited size of previous data sets.

By analyzing data representing more than 70,000 individuals worldwide — generated through TGen’s online cognitive test called MindCrowd — the current study produced results that indicate definitive trends.

“These results suggest that smoking and cardiovascular disease impact verbal learning and memory throughout adulthood, starting as early as age 18,” said Matt Huentelman, Ph.D., TGen Professor of Neurogenomics, a MindCrowd founder, and the study’s senior author.

“Smoking is associated with decreased learning and memory function in women, while cardiovascular risk is associated with decreased learning and memory function in men.”

Not well understood

Besides Alzheimer’s disease, the most significant cause of cognitive decline is known as “vascular contributions to cognitive impairment and dementia” or VCID, which arises from stroke and other vascular brain injuries that cause significant changes to memory, thinking and behavior: smoking and cardiovascular disease exacerbate VCID.

“The reasons for these sex-modification effects are not entirely understood,” said Candace Lewis, Ph.D., a Postdoctoral Fellow in Dr. Huentelman’s Lab, and the study’s lead author.

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

This study’s findings are important, Dr. Lewis said, since cigarette smoking is the nation’s leading cause of preventable disease and death, accounting for nearly 1 in 5 deaths, and cardiovascular disease is the leading cause of disease and death worldwide, and is an important predictor of cognitive decline and VCID.

Vascular diseases also are associated with increased risk of Alzheimer’s, which is the nation’s 6th leading cause of death.

Because the study included a wide range of adults, 18-85, it allowed researchers to assess the relationship between smoking, cardiovascular disease, and verbal memory in the broadest single study age range used to date.

The researchers noted that few studies have previously assessed the effects of cardiovascular disease in younger adults, and that understanding the relationship between cardiovascular disease and cognitive function in young adults may be necessary for understanding possible treatment and intervention opportunities.

Living habits are important

“This study points out some unpredicted but important differences between the sexes relating to cognitive decline,” said Brian Tiep, M.D., City of Hope director of pulmonary rehabilitation and smoking cessation.

“The impact on mental acuity seems progressive over time — some more rapid than others. Living habits related to diet, exercise and smoking certainly are consequential and may differ between men and women. People undergoing cancer care may be cognitively affected by the cancer and its treatment.”

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

Also contributing to this study were: 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, and the University of Arizona.

The study — Smoking is associated with impaired verbal learning and memory performance in women more than men — 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, and a grant from the National Institute on Aging. The TGen Foundation led philanthropic efforts to support MindCrowd.

Treat early cardiovascular risk

Treating people in early adulthood for cardiovascular risk could preserve their ability to think clearly, learn, and remember as they age, a study pooling large sets of population data suggests.

The findings showed that risk factors such as elevated body mass index, fasting glucose, and systolic blood pressure were associated with worse cognitive health later in life.

The research was published in the March 17 online issue of Neurology, the medical journal of the American Academy of Neurology.

Heart health, cognitive health linked

Existing evidence suggests that maintaining heart health, in particular blood pressure control, may slow cognitive decline, yet research to date on delaying cognitive decline has focused on reducing cardiovascular risk during midlife. To address this gap, researchers compiled data from different groups and measured the association of early adult, midlife, and late-life cardiovascular risk with late-life cognitive decline.

The research team found that across the adult life course, elevated cardiovascular risk factors, including elevated body mass index, fasting glucose, and systolic blood pressure, but not total cholesterol, were associated with greater cognitive decline in late life.

Lead author Kristine Yaffe, MD, from the University of California San Francisco, noted that the findings are particularly noteworthy because they show cardiovascular risk exposures in early life in particular are associated with late-life cognitive change, even after accounting for risk exposures in mid- and late-life.

Four studies reviewed

To get a full adult life-course perspective on cardiovascular risk factors and cognitive decline, the research team combined data from four NIH-funded studies: Coronary Artery Risk Development in Young Adults (CARDIA), Multi Ethnic Study of Atherosclerosis (MESA), Cardiovascular Health Study (CHS), and Health, Aging and Body Composition (Health ABC).

The CARDIA study included data of young to middle-aged adults, MESA of middle-aged to older adults, and the CHS and Health ABC studies of older adults. This pooled cohort included Black and White adult participants ages 18 to 95 years old at enrollment.

The researchers assigned values over time for body mass index, fasting glucose, systolic blood pressure, and total cholesterol for 15,001 adults.

Strengths and limitations

Yaffe, who recently described the importance of this kind of population-based evidence in an NIH lecture, “Epidemiology of Cognitive Aging: Why Observational Studies Still Matter,” noted a strength of this study is its large sample size and ability to study exposures over the adult life course.

Limitations described include that the missing measures of early- and mid-life cardiovascular risk were imputed and these values tended toward average levels, thereby lessening the strength of the associations with cognitive decline.

The analysis suggests that absence of cardiovascular risk factors in early adulthood is associated with better cognitive health in old age, even when midlife and late life cardiovascular factors are taken into account.

Next steps in this area of research would be to determine if treating early-life cardiovascular risk factors has an effect on cognition in late-life.


The above research was supported by NIA grants 1RF1AG054443 and K01AG047273.

The above research was supported by NIA grants 1RF1AG054443 and K01AG047273.



  • C. R. Lewis, J. S. Talboom, M. D. De Both, A. M. Schmidt, M. A. Naymik, A. K. Håberg, T. Rundek, B. E. Levin, S. Hoscheidt, Y. Bolla, R. D. Brinton, M. Hay, C. A. Barnes, E. Glisky, L. Ryan, M. J. Huentelman. Smoking is associated with impaired verbal learning and memory performance in women more than menScientific Reports, 2021; 11 (1) DOI: 10.1038/s41598-021-88923-z< br />
  • Yaffe K, et al. Cardiovascular Risk Factors Across the Life Course and Cognitive Decline: A Pooled Cohort Study. Neurology. DOI: 10.1212/WNL.0000000000011747
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B. Berger

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