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There is growing evidence that inflammation plays aAlzheimer's disease（AD) and other dementias. Some previous studies have focused on inflammatory levels in late life, but the pathological development of AD and dementia often spans decades. Is the impact of inflammation also gradually accumulated?

Previous studies exploring this issue have mostly used levels of inflammation at a single time point, and therefore have not been able to fully describe the cumulative burden of inflammation or the association between changes in inflammation levels over time and symptoms such as cognitive decline associated with AD and dementia.

To clarify this connection, the UCSF research teamyoung peopleCoronary Artery Risk Development Cohort(CARDIA) conducted an analysis and found thatCompared with stable low CRP levels over 18 years, persistently high and moderate/increasing levels were associated with a 67% and 104% increased risk, respectively, of poorer processing speed in cognitive function in midlife, and a 36% increased risk of poorer executive function.

This shows thatPersistently high or moderate/increased levels of inflammation beginning in early adulthood may be associated with impairments in executive function and processing speed beyond midlife.The research results were published in the journal Neurology [1].

CARDIA is a prospective cohort study involving 5115 participants in four cities in the United States who were aged 18-30 years and in good health when enrolled in 1985-1986. CRP, a marker of systemic inflammation, was collected at 7, 15, 20, and 25 years of follow-up, spanning more than 18 years.

Cognitive function consists of 6 areasCognitive decline was defined as a z score of ≥1 standard deviation (SD) less than the cohort mean in each domain.

This study included 2364 participants, and the CRP levels at each follow-up time point were used to determineThere were 3 trajectories of inflammation levels: persistently high, moderate/increasing, and stable low, accounting for 39.0%, 16.0%, and 45.0%, respectively.

The three trajectories of inflammation levels are persistently high (green), moderate/increasing (blue), and steadily low (red).

After adjustment for age, race, sex, education, smoking, alcohol intake, physical activity, andAPOE After ε4, compared with the stable low CRP group, the persistently high and moderate/increasing groups were associated with a 67% and 104% increased risk of poorer processing speed in cognitive function, respectively, and persistently high levels were also associated with a 36% increased risk of poorer executive function.There was no significant correlation in verbal memory, fluency and overall cognition.

Uncorrected (A) and Corrected（B）Associations between inflammation trajectory and cognitive functions after confounding factors

In sensitivity analyses, the researchers further adjusted forBMI, the results did not change significantly. In addition, the association between inflammation trajectory and cognitive function was different for race andAPOE There was no significant interaction with ε4.

In summary, persistently elevated and moderate/increasing levels of inflammation compared with stable low levels starting in early adulthood are associated with an increased risk of poor cognitive function in midlife, and the main cognitive functions that may be affected are processing speed and executive function after adjusting for multiple confounders.

Researchers believe that inflammation ishypertension,highcholesterol、obesityanddiabetesetc.Cerebrovascular diseaseIt is a risk factor for cognitive impairment and may affect cognitive function through vascular pathways. In addition, chronic inflammation can lead to neurodegeneration and death of neurons and damage neurogenesis. Studies have also found that CRP-mediated increased blood-brain barrier permeability may also be a key mechanism for the association between inflammation and cognitive aging. The specific mechanism needs to be verified in future studies.

Kristine Yaffe, a researcher involved in this study and professor at the University of California, San Francisco, said that inflammation plays an important role in cognitive aging, with both direct and indirect effects. Fortunately, there are ways to reduce inflammation, such as increasing exercise and reducing smoking. She hopes these can become a preventive measure for cognitive aging.Professor Yaffe was part of the research team that first proposed that “30% of dementia cases can be prevented”. One of their current research focuses is the impact of personalized health and lifestyle interventions on preventing memory loss in high-risk elderly people [2].

Referencesoffer:

[1] Bahorik A L, Hoang T D, Jacobs D R, et al. Association of Changes in C-Reactive Protein Level Trajectories Through Early Adulthood With Cognitive Function at Midlife: The CARDIA Study[J]. Neurology, 2024, 103(2): e209526.

Author: Ying Yuyan