Metabolic Syndrome and CRP Linked to Cognitive Decline

Caroline Helwick

October 18, 2013

NEW ORLEANS — According to a nationally representative sample of persons aged 60 years or older, metabolic syndrome may predispose to cognitive decline, especially when it occurs in conjunction with elevated C-reactive protein (CRP), new research suggests.

The findings add to the understanding of the association between neurometabolic disorders and cognition, said first author Zuolu Liu, BA, and their implications may be relevant to primary care, she said.

"The metabolic syndrome by itself was associated with cognitive decline, but elevated CRP was as well. The associations were very strong," said Liu, a medical student at Temple University in Philadelphia, Pennsylvania. The study's senior author was Carol Lippa, MD, professor of neurology at Temple.

The study was presented at the American Neurological Association (ANA) 2013 Annual Meeting.

NHANES Database Explored

Investigators examined information on 2975 persons 60 years of age or older (mean age, 70) in the US National Health and Nutrition Examination Survey (NHANES, 1999–2002) who had undergone a Digit Symbol Substitution Test (DSS), a standard measure of cognitive function. Cognitive decline was defined as a score in the lowest quintile of the DSS score (DSS score < 25).

Metabolic syndrome was defined as having at least 3 of 5 traits (large waist circumference, high blood pressure, elevated glucose, elevated triglycerides, and decreased high-density lipoprotein cholesterol) associated with the disorder. Serum CRP, a marker of inflammation, was also measured.

The researchers found the prevalence of the metabolic syndrome to be 37.5% and the prevalence of cognitive decline to be 12.4% in men and 11.79% in women. They saw a decrease in DSS score from younger to older age (P < 0.001) and significantly lower mean DSS scores among blacks and Hispanics than whites across all age groups (P < 0.01).

Multivariate analysis indicated that 3 metabolic syndrome traits — large waist circumference, high blood pressure, and elevated glucose — were significantly associated with cognitive decline (P < .001). A significant "dose-response" relationship was observed between increasing number of unfavorable traits (from 1 to 4 or more) and the odds of cognitive decline (P < .001). A combined effect of metabolic syndrome and CRP was also seen, Liu reported.

After adjustment for CRP, the odds ratios for each individual trait decreased slightly, but this also increased the odds ratio for a risk associated with the metabolic syndrome.

Table. Adjusted Odds Ratios of Metabolic Syndrome and Cognitive Decline*

Trait Model 1 Odds Ratio Model 1 P Value Model 2 Odds Ratio Model 2 P Value
Metabolic syndrome vs normal 1.40 .034 1.68 .001
Large waist circumference vs small 1.52 <.001 1.52 .001
High blood pressure vs low 1.49 .003 1.42 .024
Elevated glucose vs low 1.87 <.001 1.76 .001
4 or more traits vs 0 1.90 .008 2.25 0.010

* Model 1: adjusting for age, sex, race, marital status, smoking status. Model 2: adjusting for all covariates in model 1 plus CRP.


"The main findings from the study are that the metabolic syndrome significantly predicts the odds for the prevalence of cognitive decline in a nationwide representative sample of participants aged 60 years and older," she said. "Elevated CRP had a potential combined effect on risk. These associations were independent of a set of covariates."

Liu added that one third of the US population is obese, and the metabolic syndrome is on the rise. If cognitive decline is a consequence of the condition, she suspected that patients may be more willing to accept strategies for prevention.

Michael Schneck, MD, from Loyola University Medical Center in Maywood, Illinois, commented on the findings for Medscape Medical News. He noted that an association between metabolic syndrome and cognitive decline has been described in some studies, especially in the context of vascular dementia. While the current study is a cross-sectional analysis, and as such has limitations in design, NHANES is "well performed and offers the strength of a good database," he said.

He felt the study does not establish that metabolic syndrome is predictive of cognitive decline but raises the possibility that "inflammation in the context of the metabolic syndrome may be a biological modifier for the metabolic syndrome, and this may be the thing that influences cognitive decline" in these patients.

He added that because of the study limitations, "one must be cautious about making a prediction or making statements about causality."

Ms. Liu received a Travel Fellowship Award to attend the meeting but had no other disclosures. Dr. Schneck has disclosed no relevant financial relationships.

American Neurological Association (ANA) 2013 Annual Meeting. Abstract #S602. Presented October 13, 2013.


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