Midlife Cognition Tied to Inflammation Years Earlier

Inflammation in young adulthood was associated with midlife cognitive outcomes, data from the CARDIA study showed.

Compared with lower stable levels of C-reactive protein (CRP), consistently higher CRP levels over 18 years led to higher odds of poor processing speed scores in midlife (adjusted OR 1.67, 95% CI 1.23-2.26), as did moderately/increasing CRP levels (adjusted OR 2.04, 95% CI 1.40-2.96), reported Amber Bahorik, PhD, of the University of California San Francisco (UCSF), and co-authors.

Consistently higher CRP was also linked with poor executive function scores in midlife (adjusted OR 1.36, 95% CI 1.00-1.88), the researchers reported in Neurology.

Higher levels of inflammation are associated with obesity, physical inactivity, chronic illness, stress, and smoking. Inflammation levels tend to vary over the life course, and this variation over time may help predict cognitive aging, the researchers suggested.

“There is likely a direct and indirect effect of inflammation on cognition,” co-author Kristine Yaffe, MD, also of UCSF, said in a statement. “Fortunately, there are ways to reduce inflammation — such as by increasing physical activity and quitting smoking — that might be promising paths for prevention.”

Late-life inflammation has been tied to dementia risk and cognitive decline, Yaffe noted. In a recent U.K. Biobank analysis, high levels of CRP emerged as one of several risk factors for young-onset dementia.

The CARDIA research “underscores the importance of considering earlier time points when exploring the determinants of cognitive decline and the relevance of monitoring inflammation in this context,” noted Eleanor Conole, PhD, of the University of Oxford in England, in an accompanying editorial.

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

But whether CRP is the best marker to assess baseline inflammation in a population study like this isn’t clear, Conole pointed out. “CRP is an acute phase protein produced in the liver and, true to its name, is acute, phasic, and reactive,” she wrote.

Clinically, changes in CRP levels are indicators of deterioration or recovery; rising levels can signal a flare-up and decreasing levels can indicate effective treatment. “However, this phasic nature of CRP poses problems for capturing baseline inflammation in population studies, a limitation acknowledged by the authors,” Conole observed.

Bahorik and colleagues followed 2,364 adults in the ongoing CARDIA study, a longitudinal cohort study that started in 1985 to evaluate determinants of cardiovascular disease and their risk factors. About half the participants were female; a little under half were Black, and the rest were white. Participants with elevated levels of inflammation (CRP of 10 mg/L or more) were excluded from the study.

CRP was measured at four time points over 18 years when people were from ages 24 to 58 years. Inflammation trajectories that reflected overall patterns showed that 39% of participants had consistently higher CRP, 16% had moderate/increasing CRP, and 45% had lower stable CRP.

Five years after the last CRP measurement, the researchers administered a battery of six cognitive tests to assess verbal memory, processing speed, executive function, verbal and category fluency, and global cognition. Participants were ages 47 to 63 when they were tested. Poor cognitive performance was defined as a decline of one or more standard deviations less than the mean on each domain.

Patterns of consistently higher and moderate/increasing inflammation were associated with slower processing speed and worse executive function after controlling for demographics, lifestyle risk factors, and APOE4. “Participants with a pattern of consistently higher inflammation were most likely to have higher odds of poor cognitive function,” Bahorik and colleagues noted. “There was no association of inflammation trajectory and impairment in memory, fluency, or global cognition.”

Limitations of the research included possible selection bias due to loss of follow-up and the study’s reliance on CRP as the only inflammatory marker, they acknowledged.

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