Early CVD Linked to Accelerated Cognitive Decline

Premature cardiovascular disease (CVD) was associated with accelerated decline in cognition and white matter health in midlife, a large prospective cohort study showed.

On a composite cognitive score, those with CVD events before age 60 were more than three times as likely to drop by at least 1.5 standard deviation more than the race-specific average over 5 years (OR 3.07, 95% CI 1.65-5.71), Kristine Yaffe, MD, of the University of California San Francisco, and colleagues reported in Neurology.

Among over 3,000 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, such premature CVD was significantly associated with worse cognitive function in four of five domains:

• Global cognition (-0.22, 95% CI -0.37 to -0.08)
• Verbal memory (-0.28, 95% CI -0.44 to -0.12)
• Processing speed (-0.46, 95% CI -0.62 to -0.31)
• Executive function (-0.38, 95% CI -0.55 to -0.22)

Prevalence of accelerated cognitive decline among the 2,722 participants with cognitive assessment both at year 25 and 30 in the study was 13% in those with premature CVD and 5% without premature CVD.

“Our research suggests that a person’s 20s and 30s are a crucial time to begin protecting brain health through cardiovascular disease prevention and intervention,” coauthor Xiaqing Jiang, PhD, of the University of California San Francisco, said in a statement. “Preventing these diseases may delay the onset of cognitive decline and promote a healthier brain throughout life.”

Previous research has linked CVD, such as heart disease and stroke, with an increased risk for cognitive impairment and dementia in older adults, but less has been known about how having these diseases before age 60 impacts cognition and brain health over the course of life, Jiang added. “Our study found that cardiovascular events earlier in life are associated with worse cognition, accelerated cognitive decline and poor brain health in middle age.”

CARDIA had also previously linked cardiovascular risk factors in mid-life to cognitive decline.

Over the 30-year follow-up, 4.7% of participants had at least one premature CVD event, which was defined as coronary heart disease, stroke, transient ischemic attack (TIA), congestive heart failure, carotid artery disease, or peripheral artery disease before age 60. They were an average age of 48 years at the first event, with follow-up cognitive assessment occurring an average of 7.7 years later.

Among a subset of 656 participants who had brain MRIs, developing CVD before age 60 was associated with greater white matter hyperintensities (WMH) overall and in the temporal and parietal lobes as well as higher white matter mean diffusivity overall and in the temporal lobes.

“In multivariable-adjusted models, these brain MRI parameters [with the exception of total mean diffusivity] were independently associated with worse cognitive function in several domains, including global cognition, verbal learning and memory, processing speed, and executive function,” noted Yaffe and co-authors.

The study included 3,146 participants (57% women) who were ages 18-30 years at baseline in 1985-86. At year 30 follow-up, average age was 55.1 years and mean education 15.2 years.

Cognitive Tests included the Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test, Digit Symbol Substitution Test, and Stroop Test, with the latter three also used at year 25.

“The association between premature CVD and cognitive function in some specific domains may differ by sex and race,” authors noted. “In addition, having premature CVD was associated with a greater burden of WMH and [some] alterations of white matter integrity … These associations were not entirely driven by stroke/TIA, and were independent of shared risk factors for CVD, cognitive function, and brain health, including demographics.”

Compared to participants without premature CVD, those who had premature CVD events were older and more likely to be male, Black, less educated, and to have CV risk factors.

Adjusted analyses showed significant interaction with sex such that premature CVD was significantly associated with lower verbal fluency in women (-0.35, 95% CI -0.62 to -0.08) but not in men (0.13, 95% CI -0.10 to 0.37).

A significant interaction also emerged between race and executive function (P=0.029), with stronger association among the 48% of the cohort of Black race (-0.56, 95% CI -0.83 to -0.29) compared with white race (-0.20, 95% CI -0.41 to 0.02). “We did not find evidence of an effect modification by APOE ε4 (all P>0.05),” wrote Yaffe and co-authors.

In contrast to older adults, “CVD incidence and mortality among young and middle-aged adults have been steady or increasing,” authors noted. “Indeed, about half of CVD events among men and one-third among women occur during young and middle adulthood.”

Authors acknowledged study limitations included a lack of cognitive testing at the start of the study and limited generalizability due to inclusion of only Black and white adults in this cohort.