Cognitive performance in midlife is linked to inflammation years earlier

Data from the CARDIA study suggest that inflammation in young adulthood is associated with cognitive performance in midlife.

Amber Bahoric, PhD, of the University of California, San Francisco (UCSF), and co-authors reported that compared with stable low levels of C-reactive protein (CRP), consistently high CRP levels over an 18-year period were associated with higher odds of lower processing speed scores in midlife (adjusted OR 1.67, 95% CI 1.23-2.26), with moderate/rising CRP levels similarly associated with higher odds (adjusted OR 2.04, 95% CI 1.40-2.96).

The researchers reported that consistently higher CRP was also associated with poorer executive function scores in midlife (adjusted OR 1.36, 95% CI 1.00-1.88). Neurology.

High levels of inflammation are associated with obesity, physical inactivity, chronic disease, stress, and smoking. Inflammation levels tend to change throughout life, and researchers suggest that these changes over time may help predict cognitive aging.

“Inflammation can have direct and indirect effects on cognitive function,” said co-author Christine Yaffe, M.D., Ph.D., also of the University of California, San Francisco, in a statement. “Fortunately, there are ways to reduce inflammation, such as by increasing physical activity or quitting smoking, which may offer a promising avenue for prevention.”

Yaffe noted that inflammation in older age has been linked to the risk of dementia and cognitive decline, and high levels of CRP emerged as one of the risk factors for dementia in a recent UK Biobank analysis. Early onset dementia.

The CARDIA study “highlights the importance of considering earlier time points when exploring determinants of cognitive decline and the importance of monitoring inflammation in this context,” said Dr Eleanor Conall of the University of Oxford in the UK. Accompanying editorial.

“Approaches that consider multiple immune markers in deeply phenotyped populations are strongly encouraged, and advances in the ability to measure immune function at low cost and large scale may help elucidate these relationships,” she added.

But it's not clear whether CRP is the best marker for assessing baseline inflammation in population studies like this one, Connoll noted. “CRP is an acute-phase protein produced in the liver and, as the name suggests, is acute, phasic, and reactive,” she wrote.

Clinically, changes in CRP levels are indicative of worsening or recovery, while rising levels are a sign of relapse and decreasing levels may indicate effective treatment. “However, this phasic nature of CRP poses problems for capturing baseline inflammation in population studies, a limitation that the authors acknowledge,” Conall noted.

Bahoric and his colleagues conducted an ongoing follow-up study of 2,364 adults. CARDIA ResearchA longitudinal cohort study beginning in 1985 has assessed the determinants and risk factors of cardiovascular disease. Approximately half of the participants were women, just under half were black, and the rest were white. Participants with high levels of inflammation (CRP ≥ 10 mg/L) were excluded from the study.

CRP was measured at four time points over an 18-year period when subjects were between the ages of 24 and 58. Inflammation trajectories reflecting overall patterns showed that 39% of participants had consistently high CRP, 16% had moderate/increasing CRP, and 45% had stable low CRP.

Five years after the last CRP measurement, the researchers administered six cognitive tests to assess verbal memory, processing speed, executive function, verbal and category fluency, and global cognition. Participants were between 47 and 63 years old at the time of testing. Cognitive decline was defined as a decline of more than one standard deviation below the mean in each domain.

The pattern of consistently high and moderate/increasing inflammation was consistent with demographics, lifestyle risk factors, and Apoe 4“Participants with a consistently high pattern of inflammation were most likely to experience cognitive decline,” Bahoric and his colleagues noted. “There was no association between inflammation trajectories and impairments in memory, fluency, or global cognitive function.”

Study limitations, the researchers acknowledged, include the possibility of selection bias due to loss to follow-up and the study's reliance on CRP as the only inflammatory marker.