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'Striking' association of cardiovascular risk factors with late-life cognitive decline

An increase in risk factors for cardiovascular disease (CVD) during young adulthood is associated with cognitive decline in late life, a US data analysis shows. Investigators found a "novel, striking" association between high body mass index (BMI), elevated systolic blood pressure, and high glucose levels among adults in their 20s and 30s and a doubling of the average rate of cognitive decline over a 10-year period in late life.

"These results are striking and suggest that early adulthood may be a critical time for the relationship between these health issues and late-life cognitive skills," study investigator Dr Kristine Yaffe, professor of psychiatry, neurology, and epidemiology, University of California-San Francisco, said. "It's possible that treating or modifying these health issues in early adulthood could prevent or reduce problems with thinking skills in later life," she added.

The investigators note that CVD risk factors are associated with an increased risk for cognitive decline, but little is known as to how early CVD risk factors influence late-life cognition.

To examine the impact of these risk factors on cognition, the researchers pooled data from four prospective studies: the Coronary Artery Risk Development in Young Adults (CARDIA) study, the Multi Ethnic Study of Atherosclerosis (MESA), the Cardiovascular Health Study (CHS), and the Health, Aging and Body Composition (Health ABC) study (n = 15,001 participants aged 18–95 years).

On the basis of previous epidemiologic research of CVD risk factors associated with cognitive decline, the investigators focused on BMI, fasting glucose level, systolic blood pressure, and total cholesterol level. They used data from the four studies to examine early adult and mid-life trajectories of these risk factors for each participant in the two older cohorts – those of the Health ABC and CHS studies.

To assess cognitive outcomes, the investigators examined participants' scores on the Digit Symbol Substitution Test (DSST) and the Modified Mini–Mental State Exam. The former test measures processing speed and executive function; the latter evaluates global cognition. These tests were administered every 1 to 2 years.

Levels of CVD risk factors were higher among older participants than among their younger counterparts, but smoking was more prevalent among younger participants. The mean age of the two pooled older cohorts was 72 years. BMI, fasting glucose level, and systolic blood pressure were elevated in fewer than 5% of these participants during early adulthood. Among approximately 40% of older participants, cholesterol levels were elevated at that time.

Among approximately 20% of older participants, BMI and systolic blood pressure were elevated at mid-life. At mid-life, fasting glucose levels were elevated for 10% of participants, and cholesterol levels were elevated for 68%.

In late life, BMI was elevated for 15% of participants, fasting glucose levels were elevated for 9%, systolic blood pressure was elevated for 24%, and cholesterol levels were elevated for 43%.

Elevated BMI during early adulthood was associated with an increase in cognitive decline of three to four points over 10 years in late life. High systolic blood pressure was associated with a four-point increase in decline on DSST in late life.

Although fasting glucose levels were elevated in few participants during early adulthood, the data suggest such elevations are associated with increased late-life cognitive decline.
However, high cholesterol levels in early adulthood were not a significant risk factor for cognitive decline.

"The evidence for cholesterol and late-life cognitive decline is mixed, but our findings may suggest that other cardiovascular risk factors, like blood pressure, BMI, and fasting glucose in early adulthood, are more critical than cholesterol," said Yaffe.

The associations between elevated cardiovascular risk factors at mid-life and cognition in late life were less consistent. Elevated BMI, systolic blood pressure, and fasting glucose levels in late life were associated with cognitive gains in very late life.

"Clinicians could be more aware that cardiovascular health is important for brain health, even if you're not an older adult, and also share this information with their patients," said Yaffe.

Yaffe added that her team plans to investigate associations between CVD risk factors and cognition throughout life. In particular, they want to examine the transition of cognitive changes from mid- to late life, said Yaffe. "We also feel it's very important to investigate disparities in these relationships by race and ethnic groups," she said.

Medscape Medical News reports that commenting on the findings Dr Clinton Wright, director of the division of clinical research and associate director of the National Institute of Neurological Disorders and Stroke, noted that it's "very important to have this type of data measuring vascular risk factors as early as possible in life and following people for cognitive outcomes."

The study findings suggest that the presence of vascular risk factors in early adulthood and mid-life are important, he added. "They used a global measure of general cognition and a test of processing speed to measure cognition, so while suggestive of cognitive status at follow-up, performance on these tests is not equivalent to a diagnosis of cognitive impairment or dementia," he noted.

The researchers used imputation to estimate the effect of the presence of risk factors during early adult life on cognition in late life. Although they found that imputed early-life vascular risk factors were associated with greater late-life cognitive decline, "it is very important to realize that no one that was in the young adult category was followed until late life," said Wright.

Because treatment of modifiable vascular risk factors can prevent vascular and related cognitive outcomes, it is important to know how early these risk factors start to have an effect.

"Since this study is not a clinical trial and is observational and is a pooled analysis of multiple studies where people were not followed from young adult to late life, more data from longitudinal studies are necessary to confirm these findings," said Wright. "But we may never have a definitive trial, since it is not practical to study large groups of people for decades in the context of a treatment trial."

One question for future study concerns how the presence of risk factors during early adulthood, including the intensity and duration of these risk factors, affects hard cognitive outcomes, such as mild cognitive impairment and dementia, said Wright.
Another question to investigate is how social determinants of health and access to care modify or moderate the effects of these risk factors in different populations and racial and ethnic groups.


Study details
Cardiovascular Risk Factors Across the Life Course and Cognitive Decline: A Pooled Cohort Study

Kristine Yaffe, Eric Vittinghoff, Tina Hoang, Karen Matthews, Sherita H Golden, Adina Zeki Al Hazzouri

Published in Neurology on 17 March 2021

Cardiovascular risk factors (CVRFs) are associated with increased risk of cognitive decline, but little is known about how early adult CVRFs and those across the life course might influence late-life cognition. To test the hypothesis that CVRFs across the adult life course are associated with late-life cognitive changes, we pooled data from four prospective cohorts(n=15,001, ages 18-95).
We imputed trajectories of body mass index (BMI), fasting glucose (FG), systolic blood pressure (SBP), and total cholesterol (TC) for older adults. We used linear mixed models to determine the association of early adult, mid-life, and late-life CVRFs with late-life decline on global cognition (Modified Mini-Mental State Exam (3MS)) and processing speed (Digit Symbol Substitution Test (DSST)), adjusting for demographics, education, and cohort.
Elevated BMI, FG, and SBP (but not TC) at each time period were associated with greater late-life decline. Early life CVRFs were associated with the greatest change, an approximate doubling of mean 10-year decline (an additional 3-4 points for 3MS or DSST). Late-life CVRFs were associated with declines in early late-life (<80 years) but with gains in very late-life (≥80 years). After adjusting for CVRF exposures at all time periods, the associations for early adult and late-life CVRFs persisted.
We found that imputed CVRFs across the life course, especially in early adulthood, were associated with greater late-life cognitive decline. Our results suggest that CVRF treatment in early adulthood could benefit late-life cognition, but that treatment in very late-life may not be as helpful for these outcomes.


Full Medscape Medical News report (Open access)

Neurology study (Restricted access)

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