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Researchers reported that— after adjustments were made for age, sex, race, marital status, and smoking status — survey respondents with metabolic syndrome had an odds ratio of 1.40 for cognitive decline — defined as scoring in the lowest fifth in the Digit Symbol Substitution Test — compared to those without metabolic syndrome (p=.034).
NEW ORLEANS — An analysis of data on thousands of older patients from a national database has provided more evidence that metabolic syndrome is associated with cognitive impairment, with elevated glucose associated with the greatest risk of the five metabolic syndrome elements, according to a study presented here at the annual meeting of the American Neurological Association.
[The five elements include a large waistline, a high triglyceride level, a low HDL cholesterol level, high blood pressure, and high fasting blood sugar.]
The research team from Drexel University and Temple University also found that an elevated amount of the inflammatory marker C-reactive protein (CRP) presents an independent risk associated with cognitive decline and that someone with both factors working against them are more likely to have lower scores on cognitive testing.
Researchers examined information collected in the National Health and Nutrition Examination Survey, a set of studies conducted by the Centers for Disease Control and Prevention, to assess the health and nutrition of US adults and children. The survey combines both interviews and physical exams.
The researchers looked exclusively at data on 2,975 people, ages 60 and older, who had completed the Digit Symbol Substitution Test (DSST), a test of cognition in which participants are asked to match digits with their corresponding symbols from a reference list. They reviewed data from 1999 to 2002 because those were the latest years in which the DSST was included in the survey, said Zuolu Liu, a senior medical student at Temple University School of Medicine, who worked on the study with Carol Lippa, MD, professor of neurology at Drexel University College of Medicine.
They found that — after adjustments were made for age, sex, race, marital status, and smoking status — the survey respondents with metabolic syndrome had an odds ratio of 1.40 for cognitive decline — defined as scoring in the lowest fifth in the DSST — compared to those without metabolic syndrome (p=.034). Lower scores on the DSST, which measures response speed, sustained attention, and visualspatial skills, are associated with cognitive decline.
Odds ratios for the individual traits of metabolic syndrome varied widely. For elevated glucose compared to low glucose, it was 1.87 (p<.001). For large waist circumference compared to small, it was 1.52 (p<.001). For high blood pressure to blood pressure that is not high, it was 1.49 (p=.003).
There was no significant difference for low high-density lipoprotein (HDL) compared to higher levels, or for elevated triglycerides compared to lower levels.
The more traits of metabolic syndrome a survey respondent had, the higher the odds of cognitive decline, with the odds ratio reaching statistical significance at three out of five (OR 2.02; p=.026 after adjustments). With four factors, the odds ratio was 2.25 (p=.010).
Researchers also adjusted for CRP to determine whether metabolic syndrome was related to CRP in its effects on cognitive impairment.
“I was trying to see if it is the metabolic syndrome that leads to inflammatory factor then leads to cognitive decline or [if] they are two separate factors that go in separate ways leading to cognitive decline,” Liu said.
Researchers found that they were independent factors — metabolic syndrome still had a sizable effect on the odds of cognitive decline, even without CRP. After adjustment for CRP, the odds ratios for each metabolic syndrome trait declined slightly, but the OR for metabolic syndrome itself rose to 1.68.
But metabolic syndrome and elevated CRP seem to work in combination in affecting cognition: survey participants with both metabolic syndrome and elevated CRP scored lower on the DSST than those with just one of those conditions or neither one.
“These findings add to growing evidence that aggressively controlling metabolic syndrome and CRP may offer an important primary prevention strategy to prevent or attenuate cognitive decline in the elderly,” researchers wrote.
Liu said that paying attention to specific parameters might be especially important.
“Probably we should pay more attention to high blood sugar, pay more attention to blood pressure and cholesterol levels, and hopefully that will lower or even slow down cognitive decline,” she said.
David S. Knopman, MD, professor of neurology at the Mayo Clinic in Rochester, MN, who specializes in dementia and does epidemiological research, said the study is confirmatory but doesn't break new ground.
He said he thinks metabolic syndrome might be the wrong thing to focus on.
“There's no question that metabolic syndrome has some bearing on cognition but the point is that it's not all that potent and my view of it is that its elements are more important than its sum, at least as far as cognition and as far as the brain,” he said. Diabetes and high blood pressure play a big role in cognition, but cholesterol levels do not, and looking at the whole syndrome “doesn't buy you very much conceptually or prediction-wise.”
An Annals of Neurology study published earlier this year, which looked at the American Heart Association's “Life's Simple 7” for improving heart health — things like exercising, eating better, and losing weight — found that the more people adhered to the seven lifestyle factors, the better their cognitive performance was, he noted.
“Viewing the seven, each as individual features, and being able to look at them in a graded fashion, is actually more informative,” Dr. Knopman said.
He noted that while CRP has been found previously to have an additive effect with metabolic syndrome traits on cognition, it might not be the best indicator either. “CRP is non-specific and the problem is, it is a terribly noisy marker,” he said.
Edward Lee, MD, PhD, assistant professor of pathology and laboratory medicine at the University of Pennsylvania, who specializes in neuropathology and has studied obesity and metabolic syndrome's effects on the brain, cautioned that the data involved in the study represent a snapshot, not an assessment over time.
“They are not measuring cognitive decline, per se, but rather poor cognitive function at a given point in time,” Dr. Lee said. “In the case of Alzheimer's disease, there are dynamic changes in body weight, which are associated with increased risk for Alzheimer's disease (AD). Midlife obesity is associated with increased risk for later dementia and AD, while weight loss in the elderly is strongly associated with AD. Understanding these dynamic changes will require additional longitudinal studies that build on the associations observed in this study.”
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