Central Obesity in Midlife an Independent Risk Factor for Dementia

Caroline Cassels

March 27, 2008

March 27, 2008 — Just as having a big belly increases the risk for cardiovascular disease and diabetes, new research shows that central obesity in midlife is also an independent risk factor for dementia — a finding that also applies to individuals who are not overweight.

A large, population-based study from researchers at Kaiser Permanente Division of Research, in Oakland, California, shows that the presence of central obesity in midlife almost triples dementia risk in later life, independent of diabetes, stroke, hypertension, hyperlipidemia, and heart disease.

The longitudinal analysis of 6583 individuals in northern California who had abdominal fat measurements taken in their 40s showed that, 36 years later, those in the highest quintile of abdominal fat had an odds ratio for dementia of 2.72 compared with those without abdominal obesity.

"More than total body weight, it is where you carry your weight — especially in midlife — that elevates dementia risk," first author Rachel A. Whitmer, PhD, told Medscape Neurology & Neurosurgery.

The study is published online March 26 in Neurology.

Belly Fat More Detrimental

Recent research has also shown that midlife obesity, measured by body-mass index (BMI), increases the risk for dementia, Alzheimer's disease (AD), and neurodegenerative changes.

Previous research by Dr. Whitmer and colleagues looking at the effect of midlife BMI demonstrated that total body weight is a strong predictor of dementia, conferring a 75% increased risk among those with the highest BMI.

It is also well established that central obesity is an independent and more potent risk factor than total body obesity for type 2 diabetes, insulin resistance, coronary heart disease, stroke, and mortality.

However, said Dr. Whitmer, it was not clear whether central obesity confers a similar elevated risk with respect to dementia as it does with cardiovascular disease and diabetes.

The study included individuals from the Kaiser Permanente Medical Care Program of Northern California who participated in voluntary periodic multiphase checkups between 1954 and 1973 when they were 40 to 45 years old.

The collected data included measurements of sagittal abdominal diameter (SAD) as an indicator of central obesity, thigh circumference as a measurement of peripheral obesity, and BMI. Diagnoses of dementia were obtained from medical records an average of 36 years later.

According to Dr. Whitmer, the large sample size allowed researchers to look at the effects of a large belly above and beyond the effects of total weight. As a result, study subjects were categorized by BMI as well as SAD.

Large Effect

The study revealed that individuals who were both obese and who had a large belly were 3.6 times more likely to develop dementia than those of normal weight and belly size. However, even subjects with a normal BMI but who had a high SAD were 89% more likely to develop dementia.

"I was surprised by the magnitude of our findings. I thought that once we took into account other cardiovascular risk factors, particularly diabetes, the impact of belly fat would have been attenuated. But instead, we found people who were obese and who had a large belly had a hazard ratio of 3.6, which is huge relative to the effect of BMI alone [on dementia risk]," she said.

Of the total study group, 1049 (16%) participants developed dementia. Age-adjusted incidence rates of dementia by quintiles of SAD showed an increase in dementia risk across quintiles, with a steep increase in incidence among those in the fifth quintile.

Fully adjusted multivariate analyses showed that SAD increased dementia risk in a dose-dependent fashion so that individuals in the second quintile were 20% more likely to have dementia, those in the third quintile 49% more likely to have dementia, those in the fourth quintile 67% more likely to have dementia, and those in the fifth quintile 2.72 times more likely to develop dementia vs those in the first quintile of SAD, the authors report.

The Good News

The study findings, said Dr. Whitmer, suggest there may be something particular about visceral adipose tissue relative to other types of body fat that contributes to poor outcomes, raising the risk for diabetes, stroke, cardiovascular outcomes, and now dementia.

"We know visceral adipose tissue is highly metabolically active and secretes hormones and inflammatory products that play a role in insulin resistance, diabetes, and cardiovascular disease, but at this point we don't know what they do to the brain," she said.

She added that some mechanistic research suggests such substances including interleukin 6 and leptin play a role in cognitive function. Leptin has been shown in animal studies to cross the blood-brain barrier and may play a role in neurodegeneration, including contributing to deposition of beta amyloid.

However, she added, more research is needed to elucidate potential mechanisms. In the meantime, clinicians should be aware of waist circumference as a potential risk factor for dementia and have a sense of whether their patients are carrying excess abdominal weight.

The good news in all of this, said Dr. Whitmer, is that "although visceral fat is more active and more toxic, studies have shown that it responds well to diet and exercise and actually responds better than other types of body fat."

The study was supported by the National Institutes of Health. The authors report no conflicts of interest.

Neurology. Published online March 26, 2008.

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