Metabolic Syndrome Linked to Cognitive Decline in Older Adults

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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 ( & #8805;150 mg/dL);

* Low HDL-C level (women <50 mg/dL and men <40 mg/dL); and

* Hyperglycemia (glucose & #8805;110 mg/dL) or nonfasting glycemia (glucose

& #8805;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

---

, 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