Early Inflammation Linked to Cognitive Decline in Middle Age

Resume: A new study finds that higher inflammation in young adults is associated with decreased cognitive function in middle age. Researchers found that inflammation from factors such as obesity and smoking can affect memory and processing speed.

This link, previously noted in older adults, now extends into early adulthood, suggesting long-term effects on brain health. Reducing inflammation through lifestyle changes may help prevent cognitive decline.

Key Facts:

  1. Impact of inflammation: Increased inflammation in young adults is associated with poorer cognitive performance in middle age.
  2. Study data: 2,364 adults were followed for 18 years, with inflammation and cognitive skills measured.
  3. Precautionary actions: Physical activity and smoking cessation can reduce inflammation and possibly prevent cognitive decline.

Source: UCSF

Increased inflammation in young adults is associated with poorer performance on ability tests in middle age.

A new study from UC San Francisco finds that young adults with higher levels of inflammation, which is linked to obesity, physical inactivity, chronic disease, stress and smoking, may suffer from decreased cognitive function in middle age.

Previously, researchers have linked higher inflammation in older adults to dementia, but this is one of the first studies to link inflammation in early adulthood to decreased cognitive ability in middle age.

This shows brains.
The researchers also linked higher levels of inflammation to physical inactivity, higher BMI and current smoking. Credit: Neuroscience News

“We know from long-term studies that it can take decades for changes in the brain that lead to Alzheimer’s disease and other dementias to develop,” said lead author Amber Bahorik, PhD, of UCSF’s Department of Psychiatry and Behavioral Sciences and the Weill Institute for Neurosciences.

“We wanted to investigate whether health and lifestyle habits in early adulthood play a role in cognitive skills in middle age, which in turn may influence the risk of dementia later in life.”

In their study they publish in Neurology On July 3, researchers found that only 10% of people with low inflammation performed poorly on tests of processing speed and memory, compared to 21% and 19% of people with moderate or higher inflammation, respectively.

When researchers took into account factors such as age, physical activity and total cholesterol, differences in processing speed remained. Researchers also found differences in executive functions, including working memory, problem solving and impulse control.

The study followed 2,364 adults in the CARDIA study, which aims to identify factors in young adulthood that lead to cardiovascular disease two to three decades later.

Participants were 18 to 30 years old when they started the study and were tested for the inflammatory marker C-reactive protein (CRP) four times over an 18-year period. They took the cognitive tests five years after their last CRP measurement, when most participants were in their 40s and 50s.

About half of the participants were women; slightly less than half were black and the rest were white. About 45% had lower stable inflammation, while 16% had moderate or increasing inflammation; 39% had higher levels.

A link between inflammation and health risks

The researchers also linked higher inflammation levels to physical inactivity, higher BMI and smoking.

“Inflammation plays a major role in cognitive aging and can begin in early adulthood,” said lead author Kristine Yaffe, MD, a professor of psychiatry and behavioral sciences, neurology, and epidemiology and biostatistics at UCSF. “There is likely a direct and indirect effect of inflammation on cognition.”

Yaffe is part of the first team of experts to find that 30% of dementia risk is preventable. Her recent research has examined the association between fragmented sleep and lower cognition in midlife and the effects of personalized health and lifestyle changes in preventing memory decline in higher-risk older adults.

“Fortunately, there are ways to reduce inflammation, such as increasing physical activity and quitting smoking, which may be a promising way to prevent the disease,” Yaffe said.

Co-authors: Tina Hoang, MSPH, of the Northern California Institute for Research and Education; David R. Jacobs, PhD, of the University of Minnesota; Deborah Levine, MD, PhD, of the University of Michigan, Ann Arbor.

Financing: See the article.

Disclosures: Yaffe reports serving on the Data Safety Monitoring Board for Eli Lilly and several National Institute on Aging-sponsored studies, providing consulting services for Alpha Cognition, serving on the board of directors of Alector Inc., providing data, safety and monitoring services for the Dominantly Inherited Alzheimer Network Trials Unit, and serving on the Beeson Scientific Advisory Board and the Global Council on Brain Health.

About this news on cognitive decline and inflammation research

Author: Suzanne Leigh
Source: UCSF
Contact: Suzanne Leigh -UCSF
Image: The image is attributed to Neuroscience News

Original research: Closed access.
“Association between changes in C-reactive protein level trajectories during early adulthood and cognitive function in middle age: the CARDIA study” by Amber Bahorik et al. Neurology


Association between changes in C-reactive protein level trajectories during early adulthood and cognitive function in middle age: the CARDIA study

Background and objectives

Inflammation in later life has been associated with risk of dementia and preclinical cognitive decline, but less is known about inflammation in early life and whether it may influence cognition in midlife. We aimed to identify levels of inflammation through early adulthood and determine the association of these pathways with cognition in midlife.


We used data from the Coronary Artery Risk Development in Young Adults study to identify inflammatory pathways (C-reactive protein [CRP] level

Six cognitive domains were assessed from tests of verbal memory, processing speed, executive function, verbal and category fluency, and global cognition; poor cognitive performance was defined as a decline of ≥1 SD less than the mean on any domain. The primary outcome was poor cognitive performance. Logistic regression was used to adjust for demographics, smoking, alcohol use, physical activity, and APOETY 4 state.


Among 2,364 participants, the mean (SD) age was 50.2 (3.5) years; 55% were female and 57% were white. Three CRP trajectories emerged over 18 years: lower stable (45%), moderate/increasing (16%), and consistently higher (39%). Compared with lower stable CRP, both were consistently higher (adjusted odds ratio [aOR] 1.67, 95% CI 1.23–2.26) and moderate/increasing (aOR 2.04, 95% CI 1.40–2.96) CRP was associated with a greater likelihood of poor processing speed; consistently higher CRP was also associated with a greater likelihood of poor executive function (aOR 1.36, 95% CI 1.00–1.88).

No association was found for memory (moderate/increasing aOR 1.36, 95% CI 1.00–1.88; consistently higher aOR 1.18, 95% CI 0.90–1.54), letter fluency (moderate/increasing aOR 1.00, 95% CI 0.69–1.43; consistently higher aOR 1.05, 95% CI 0.80–1.39), category fluency (moderate/increasing aOR 1.16, 95% CI 0.82–1.63; consistently higher aOR 1.11, 95% CI 0.85–1.45), or global cognition (moderate/increasing aOR 1.16, 95% CI 0.82–1.63; consistently higher aOR 1.11, 95% CI 0.85–1.45). perceived.


Consistently higher or moderate/increasing inflammation beginning in early adulthood may lead to poorer executive function and processing speed in midlife. Study limitations include selection bias due to loss to follow-up and reliance on CRP as the sole marker of inflammation. Inflammation is important for cognitive aging and may begin much earlier than previously known.

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