Metabolic Syndrome Linked to Cognitive Decline in Older Adults


February 3, 2011 — In a study of generally healthy adults 65 years and older, those with metabolic syndrome were significantly more likely than those without to experience a decline in cognitive function during the next 4 years, independent of previous cardiovascular disease, depression, or APOE4 genotype.

In particular, hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels were associated with declines in global cognitive function, and diabetes was associated with declines in memory.

The study was published online February 2 in Neurology.

“Our study sheds new light on how metabolic syndrome and the individual factors of the disease may affect cognitive health,” study author Christelle Raffaitin, MD, of the French National Institute of Health Research in Bordeaux, France, noted in a statement from the American Academy of Neurology. “Our results suggest that management of metabolic syndrome may help slow down age-related memory loss or delay the onset of dementia.”

The French Three-City Study

The findings stem from 4-year follow-up data on 7087 community-dwelling, dementia-free adults 65 years and older participating in the French Three-City (3C) Study, a prospective cohort study examining vascular risk factors for cognitive impairment and dementia.

At baseline and at least 1 other time during follow-up, participants completed the Mini-Mental State Examination (MMSE) for global cognitive functioning, the Benton Visual Retention Test (BVRT) for visual working memory (executive function), and the Isaacs Set Test (IST) for verbal fluency (semantic memory).

Of the 7087 study subjects, 1121 (15.8%) had metabolic syndrome, defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria, which requires the presence of 3 or more of the following:

  • Elevated blood pressure (systolic >130 mm Hg or diastolic >85 mm Hg) or use of antihypertensive medication;
  • Large waist circumference (women >88 cm and men >102 cm);
  • Elevated triglycerides levels (?150 mg/dL);
  • Low HDL-C level (women <50 mg/dL and men <40 mg/dL); and
  • Hyperglycemia (glucose ?110 mg/dL) or nonfasting glycemia (glucose ?200 mg/dL) or antidiabetic medication.

At baseline, subjects with metabolic syndrome had significantly lower scores on the MMSE, IST, and BVRT. During follow-up, the proportion of subjects who declined on the 3 tests was greater in the metabolic syndrome group; however, this was only significant for the MMSE.

Table 1. Baseline Cognitive Scores and Percentage Who Declined by Metabolic Syndrome Status

Cognitive Test Metabolic Syndrome ( n = 1121) No Metabolic Syndrome (n = 5966) P
Baseline MMSE score 27.1 27.5 <.0001
% Declining on MMSE 30.9 27.4 .01
Baseline IST 30 score 46.4 48.7 <.0001
% Declining on IST 30 28.1 27.4 .65
Baseline BVRT score 11.2 11.6 <.0001
% Declining on BVRT 36.9 35.8 <.49

BVRT = Benton Visual Retention Test; IST = Isaacs Set Test; MMSE = Mini-Mental State Examination

The prevalence of the APOE e4 allele did not differ between the 2 groups. Subjects with metabolic syndrome were more likely to be current or former smokers and to have a history of cardiovascular disease and depressive symptoms.

Elevated Triglycerides, Low HDL-C Levels Key

After adjustment for age, sex, education, smoking, cardiovascular disease, APOE genotype, depression, and other factors, those with metabolic syndrome had a significantly increased risk of showing a decline on the MMSE (22%) and BVRT (13%) but not on the IST (11%), the investigators report.

Table 2. Risk for Cognitive Decline With Metabolic Syndrome at Baseline

Cognitive Test Hazard Ratio (95% CI) P
MMSE 1.22 (1.08 – 1.37) .001
BVRT 1.13 (1.01 – 1.26) .03
IST 1.11 (0.95 – 1.29) .18

BVRT = Benton Visual Retention Test; CI = confidence interval; IST = Isaacs Set Test; MMSE = Mini-Mental State Examination

Among individual components of the syndrome, hypertriglyceridemia (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.00 – 1.26) and low HDL-C level (HR, 1.20; 95% CI, 1.04 – 1.38) were significantly associated with greater decline on the MMSE; diabetes (but not elevated fasting glucose level) was significantly associated with greater decline on the BVRT and IST.

More Study Needed

What makes the current analysis unique in the context of studies on metabolic syndrome and cognitive decline is “the large number of participants in this study (over 7000) and that different cognitive functions were evaluated with specific neuropsychological tests,” Dr. Raffaitin told Medscape Medical News. At the same time, however, the researchers note in their report that the definition of cognitive decline as assessed by the MMSE, BVRT, and IST is “debatable.”

Dr. Raffaitin said it would be worthwhile to investigate “more precise relations between each component of metabolic syndrome and specific cognitive function,” as well as conduct “interventional and not only observational” studies to see whether intensive management of metabolic syndrome may help slow age-related cognitive decline.

Reached for comment, Pirjo Komulainen, PhD, of the Kuopio Research Institute of Exercise Medicine in Finland, who was not involved in the study, called it “adequately performed.” However, Dr. Komulainen adds, “The authors are right in that the cognitive tests used are not sensitive enough.”

Still, the 3C Study findings build on several prior studies linking metabolic syndrome to cognitive decline, including a small longitudinal study by Dr. Komulainen and colleagues that linked metabolic syndrome with poorer memory at follow-up in 101 elderly Finnish women (Dement Geriatr Cogn Disord. 2007;23:29-34).

In addition, in a previous analysis of the 3C Study cohort, Dr. Raffaitin’s team found that subjects with metabolic syndrome had a significantly increased risk of developing vascular dementia but not Alzheimer’s disease.

But in Dr. Komulainen’s opinion, the current study “has not paid attention to 1 very important factor, ie, physical activity/exercise.” A recent randomized controlled intervention study by Dr. Komulainen and colleagues suggested that higher levels of fitness may potentially mitigate memory impairment (Eur Geriatr Med. 2010;1:266-272).

The study was conducted under a partnership agreement between the French National Institute of Health Research (INSERM), the University Victor Segalen Bordeaux 2, and Sanofi-Aventis. The 3C Study was supported by the National Fund for Health Insurance for Employees, Directorate General of Health, Mutual General Education, the Institute of Longevity and Aging, Regional Councils of Aquitaine and Bourgogne, and the Foundation of France. The Lille Genopole was supported by an unconditional grant from Eisai. Dr. Raffaitin has disclosed no relevant financial relationships. A complete list of financial disclosures for the other authors can be found with the original article. Dr. Komulainen has disclosed no relevant financial relationships.

Neurology. Published online February 2, 2011

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