Cardiovascular Risk Factors Tied to Midlife Cognitive Decline

Erik Greb

July 15, 2020

Cardiovascular risk factors (CVRFs), including hypertension, diabetes, and smoking, are linked to a significantly increased risk for cognitive decline in midlife in a dose-dependent manner, new research shows.

The findings suggest that the relationship between CVRFs and cognition becomes evident much earlier than previously realized. Investigators found that individuals who smoked were 65% more likely to have accelerated cognitive decline, those with hypertension were 87% more likely, and individuals with diabetes had nearly a threefold increased risk.

Dr Kristine Yaffe

"What is new here is that almost no one has looked at cardiovascular risk factors in such a young age (mean, 50) and cognitive change in middle age from 50 to 55 or so. Almost all other studies have looked at mid- or late-life cardiovascular risk factors and late-life cognition or dementia," study investigator Kristine Yaffe, MD, told Medscape Medical News.

The research was published online July 15 in Neurology.

New Insight

Previous research has shown a strong association between CVRFs and a greater risk for cognitive decline and dementia in late life, but the investigators note that data about the influence of CVRFs on cognition in midlife are "sparse."

Longitudinal studies have also shown that several cognitive domains ― particularly processing speed and executive function ― may start to decline in midlife, but whether CVRFs, many of which also emerge in midlife, contribute to these changes is unclear.

To assess the effect of CVRFs on cognitive changes in midlife, the investigators analyzed data from the ongoing Coronary Artery Risk Development in Young Adults (CARDIA) study.

CARDIA is a multicenter longitudinal study designed to measure risk factors for coronary artery disease in a large cohort of Black and White men and women.

The analysis was based on data from 2675 participants who underwent CVRF assessment and cognitive testing at baseline and 5 years later. At baseline, participants' mean age was 50.2 years. Approximately 57% of participants were women, 55% were White, and the mean number of years of education was 15.

At study outset, 43% (n = 1133) of participants were considered obese, 31% (n = 826) had hypertension, 15% (n = 701) were current smokers, 11% (n = 290) had diabetes, and 9% (n = 248) had high cholesterol.

Cognition was assessed using the Digit Symbol Substitution Test, which measures processing speed and executive function; the Stroop Test, which measures executive function; and the Rey Auditory Verbal Learning Test, which measures verbal memory.

Dose-Dependent Effect

Overall results showed that for 5% of participants, cognitive decline was accelerated at 5 years.

In unadjusted models, the odds of developing accelerated cognitive decline over 5 years was associated with hypertension (7.5% vs 4.3%; odds ratio [OR] =1.79, 95% CI, 1.27 – 2.52), diabetes (10.3% vs 4.7%; OR = 2.33; 95% CI, 1.53 – 3.56), and smoking (7.7% current smokers vs 4.3% never-smokers; OR = 1.87; 95% CI, 1.21 – 2.90). After adjusting for age, sex, and race, the associations remained significant.

The researchers found no significant effect of high cholesterol (6.9% vs 5.2%; OR = 1.35; 95% CI, 0.80 – 2.28) or obesity (6.1% vs 4.8%; OR = 1.29; 95% CI, 0.92 – 1.82) on accelerated cognitive decline.

Compared to participants with no CVRFs, the likelihood of accelerated cognitive decline was higher for individuals with one or two risk factors (OR, 1.94; 95% CI, 1.16 – 3.25) and was higher still for those with three or more risk factors (OR, 3.51; 95% CI, 2.05 – 6.00).

The fact that there was no association between midlife cognitive decline and obesity or high cholesterol did not come as a surprise, said Yaffe.

"Most studies have not shown a consistent finding with high cholesterol and later-life cognition, so it is not surprising we did not see one in midlife, when there is not as much cognitive change."

The study's results, said Yaffe, provide physicians with another good reason to help patients address CVRFs and to work with them to lower blood pressure, stop smoking, reduce diabetes incidence, or control diabetes.

Yaffe said she and her colleagues plan further research into CVRFs and accelerated cognitive decline.

"We want to know if this earlier cognitive decline [in midlife] is connected to greater decline later in life. We also want to know if improving these risk factors in midlife might prevent or slow dementia later."

More to Explore

Commenting on the findings for Medscape Medical News, Michelle M. Mielke, PhD, professor of epidemiology and neurology at Mayo Clinic College of Medicine in Rochester, Minnesota, said one of the study's main implications "is that the prevention and treatment of midlife hypertension and diabetes and smoking cessation directly impacts shorter-term changes in cognition."

She added that the study also provides a foundation for answering further questions about the effects of CVRFs on cognition in midlife.

For example, questions about sex differences remain unanswered. Men develop CVRFs earlier than women, but the investigators did not provide the prevalence of cardiovascular risk factors by sex, said Mielke.

"It was also not reported whether a specific midlife cardiovascular risk factor was more strongly associated with accelerated cognitive decline for women or for men," she said.

In addition, the mean age of the population at baseline is the approximate age of the onset of menopause, after which cardiovascular risk factors increase among women.

"Additional research is needed to understand the emergence of cardiovascular risk factors pre- vs post menopause on subsequent cognition and also consider the use of menopausal hormone therapy," said Mielke.

"Another future research avenue is to further understand the impact of antihypertensive and diabetes medications," she continued. "For example, in the current study, it was not clear how many [participants] with hypertension were treated vs untreated and whether this impacted subsequent cognition. Similarly, it is not known whether specific antihypertensives are more beneficial for cognition in midlife."

CARDIA is supported by the National Heart, Lung, and Blood Institute; the University of Alabama at Birmingham; Northwestern University; the University of Minnesota; and the Kaiser Foundation Research Institute. Yaffe serves on data safety monitoring boards for Eli Lilly and studies sponsored by the National Institute on Aging. She is a board member of Alector and is a member of the Beeson Scientific Advisory Board and the Global Council on Brain Health. Mielke has disclosed no relevant financial relationships.

Neurology. Published online July 15, 2020. Abstract

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