Worsening CAC Tied to Cognitive Decline in Midlife: CARDIA

Progression of coronary artery calcium (CAC) over time is linked to deteriorating cognitive function in middle-aged adults regardless of their baseline CAC score or other risk factors, according to data from the CARDIA study.

As such, repeat screening may identify patients who might be at risk for midlife cognitive decline in addition to cardiovascular disease, researchers say.

“This [study] highlights the potential clinical value of leveraging CAC information over time as a tool for early risk stratification of cognitive aging, as it reflects the cumulative impact of cardiovascular risk factors,” lead author Masayuki Teramoto, MD (Northwestern University, Chicago, IL), told TCTMD in an email. “Based on our findings, assessing CAC progression approximately every 5 to 10 years may provide meaningful clinical information beyond a single baseline CAC measurement in the midlife population, particularly for evaluating the potential risk of early cognitive aging.”

Lifetime exposure to cardiovascular disease risk factors, such as hypertension and diabetes, is known to contribute to the risk of cognitive decline and dementia, Teramoto added. “However, from my perspective as a physician, it is often difficult to quantify or assess cumulative risk across the life course in routine clinical practice.”

CAC as a marker of subclinical atherosclerosis reflects “the biological response to cumulative vascular injury, may serve as a risk indicator not only of cardiovascular disease but also of subsequent cognitive decline in midlife,” he continued. “One of the most notable findings was that CAC progression provided additional information beyond baseline CAC. This suggests that not only the presence of subclinical atherosclerosis, but also its progression over time, carries important implications for cognitive health.”

‘Strong Connection’

For the study, published last week in Circulation: Population Health and Outcomes, Teramoto and colleagues looked at 2,341 participants (mean baseline age 40.3 years; 56% female) from the longitudinal CARDIA study who had CAC measured at least twice and underwent cognitive testing (mean assessment age 59.0 years).

Over an average follow-up of 9.6 years, 26.4% of participants had CAC progression, defined as one of the following:

• CAC > 0 at follow-up among those with zero CAC at baseline
• An annualized change of at least 10 units at follow-up among those with baseline CAC between 1-100
• An annualized percent change of at least 10% among those with baseline CAC ≥ 100

Compared with participants without CAC progression, those whose CAC progressed were older, more likely to be male, had less education, and had a higher prevalence of smoking, hypertension, dyslipidemia, and obesity.

In total, 9% of participants had baseline CAC > 0, and they had lower marginal mean scores on all cognitive tests compared with those with CAC = 0. This remained true after adjustment for demographics, education, physical activity, depressive symptoms, and the APOE ε4 allele, where the association applied to lower processing speed and global cognition but not verbal memory tests. Adjusting for other CVD risk factors also did not change the correlation.

Additionally, those with baseline CAC scores of 1-99 and ≥ 100 also showed lower cognitive performance compared with those with a CAC score of 0, though this was only significant for those with baseline scores below 100.

Compared with no CAC progression, worsening CAC was associated with significant cognitive decline as defined by both the digit symbol substitution test (-0.14; 95% CI -0.23 to -0.06) and the Montreal cognitive assessment (-0.09; 95% CI -0.17 to -0.01). The latter was attenuated when the analysis was performed with further adjustment for other CVD risk factors.

Teramoto said he would like to see more research look beyond midlife to see “whether CAC and its progression are associated with subsequent dementia incidence and with structural or pathological brain changes detectable on MRI.”

Ultimately, “I hope more people recognize the strong connection between cardiovascular health and brain health,” he concluded. “Managing cardiovascular risk across the life course is closely linked to healthy aging and functional preservation across multiple organ systems, with brain health being one of the most important domains affected.”