Midlife systemic inflammation was tied to steeper late-life cognitive decline, an analysis of data from the ARIC prospective cohort showed.
Adults with elevated inflammation composite scores or elevated C-reactive protein (CRP) levels during midlife experienced steeper cognitive decline — especially in memory — over a 20-year period, reported Keenan Walker, PhD, of Johns Hopkins University in Baltimore, and co-authors, in Neurology.
These effects may be greater than those of midlife hypertension on 20-year cognitive decline when compared with previously published findings from the ARIC study, the team noted.
“While other studies have looked at chronic inflammation and its effects on the brain in older people, our large study investigated chronic inflammation beginning in middle age and showed that it may contribute to cognitive decline in the decades leading up to old age,” Walker said in a statement.
“Overall, the additional change in thinking and memory skills associated with chronic inflammation was modest, but it was greater than what has been seen previously associated with high blood pressure in middle age,” he added.
In this study, Walker and colleagues looked at 12,336 people in the ARIC (Atherosclerosis Risk in Communities) study, an ongoing, population-based prospective cohort study. Participants were evaluated over five visits from 1987 to 2013, with a median time between baseline and final cognitive assessment of 19.4 years. Women made up 56% of the sample, and 21% of the participants were black.
Participants had an average age of 56.8 at the time of baseline cognitive assessment and 75.8 at the final assessment. Cognition was assessed three times — at visits 2, 4, and 5 — with the Delayed Word Recall test, the Digit Symbol Substitution test, and the Word Fluency test. Of participants assessed at visit 2, 83% had at least one follow-up visit and 46% were assessed at visit 5.
Inflammatory biomarkers were measured in blood samples collected in visits 1 and 2. Using four inflammatory biomarkers measured at visit 1, the researchers created an inflammation composite score that incorporated fibrinogen, white blood cell count, von Willebrand factor, and factor VIII. At visit 2, participants also had CRP measured.
Overall, people with higher levels of midlife inflammatory markers in the study were older, more likely to be female and black, had greater rates of cardiovascular risk factors, and had lower baseline cognition.
Each standard deviation (SD) increase in midlife inflammation composite score was associated with an additional 20-year decline of −0.035 SD (95% CI −0.062 to −0.007) on the cognitive composite score, after adjusting for demographic variables, vascular risk factors, and comorbidities.
A similar association emerged between each SD increase in midlife CRP level and additional 20-year cognitive decline (−0.038 SD, 95% CI −0.057 to −0.019).
People who had inflammation composite scores in the top quartile had a 7.8% steeper cognitive decline than participants in the lowest quartile. Likewise, CRP in the top quartile was associated with an 11.6% steeper cognitive decline.
Elevated midlife inflammatory markers were most consistently associated with steeper declines in memory, but not executive function or language.
“Systemic infection and inflammation are common as people get older,” noted Wendy Qiu, MD, PhD, of Boston University School of Medicine, who was not part of this research.
“This large cohort study provides evidence that chronic peripheral inflammation could impact the brain, leading to cognitive decline in the elderly,” Qiu told MedPage Today. “Treating systemic inflammation while monitoring CRP changes in the middle-aged and elderly could be an effective prevention for dementia.”
“Many of the processes that can lead to a decline in thinking and memory skills are believed to begin in middle age, and it is in middle age that they may also be most responsive to intervention,” Walker added.
“Our results show that chronic inflammation may be an important target for intervention. However, it’s also possible that chronic inflammation is not a cause and instead a marker of, or even a response to, neurodegenerative brain diseases that can lead to cognitive decline.”
The study had several limitations, the researchers noted. By the final visit, 54% of the cohort had dropped out or died — most likely people with higher levels of chronic inflammation at baseline — and surviving participants may not be representative of the general population. The study’s findings were similar after adjusting for attrition using inverse probability weighting, however.
The majority of the sample also lacked more than two time points, so the dynamic trajectory of cognitive decline related to midlife inflammation could not be determined, the authors added. Unmeasured confounders also may have biased the results.
The study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases. Roche Diagnostics donated the reagents for the C-reactive protein tests.
Walker reported no disclosures relevant to the manuscript. Other researchers reported relationships with the DIAN study, Biogen, Lilly Pharmaceuticals, the Alzheimer’s Disease Cooperative Study, the CMS Coverage with Evidence Development (CED) study, and Acadia Pharmaceuticals.