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Metabolic And Neurological Disorders May Share Common Risk Factors

March 15, 2009
JAMA and Archives Journals
Metabolic disorders such as obesity and diabetes appear to share risk factors with and may influence the development of Alzheimer's disease and other forms of dementia, according to several reports published in the Archives of Neurology.

Metabolic disorders such as obesity and diabetes appear to share risk factors with and may influence the development of Alzheimer's disease and other forms of dementia, according to several reports published in the March issue of Archives of Neurology.

The issue—a theme issue on neurological disorders related to metabolic diseases—is being published in conjunction with a JAMA theme issue on diabetes, obesity and their comorbidities.

Studies featured in this issue include the following:

Women With More Components of Metabolic Syndrome More Likely to Develop Cognitive Impairment

Women with the cluster of cardiovascular risk factors known collectively as the metabolic syndrome appear likely to develop cognitive impairment over a four-year period. Kristine Yaffe, M.D., of the University of California, San Francisco, and the San Francisco Veterans' Affairs Medical Center, and colleagues assessed 4,895 older women (average age 66.2) who did not have cognitive impairment at the beginning of the study.

Of the 497 (10.2 percent) women who had the metabolic syndrome 7.2 percent (36) developed cognitive impairment during a four-year period, compared with 4.1 percent (181 of 4,398) of those who did not have the metabolic syndrome. Each additional component of the syndrome—such as abdominal obesity, high blood pressure and low HDL cholesterol levels—was associated with a 23 percent increase in risk of cognitive impairment.

"As the obesity and sedentary lifestyle epidemic escalates throughout the world, identification of the role of these modifiable behaviors in increasing risk for development of deleterious outcomes, such as cognitive impairment, is critical," the authors conclude. "Future research should assess whether identification of cognitive impairment among patients with the metabolic syndrome or more aggressive clinical control of the factors that compose the metabolic syndrome might lessen the risk of developing cognitive impairment in elderly people."

Obesity Associated With Worsening Cognitive Function in Older Men

Older men with higher levels of fat appear more likely to experience declines in cognitive function over seven years, but the same association does not appear to occur in older women. Alka M. Kanaya, M.D., of the University of California–San Francisco, and colleagues studied 3,054 elderly individuals enrolled in the Health ABC Study.

Participants' adiposity (fat level) was assessed by body mass index, waist circumference, sagittal diameter (distance between the back and the highest point of the abdomen), total fat mass and subcutaneous (beneath the skin) and visceral fat (fat between the internal organs) measured by computed tomography. Men whose measurements were higher were more likely to experience declines in scores on a cognitive functioning test administered at the beginning of the study and again after three, five and eight years. However, no association was observed in women.

"Women show trends toward inverse associations, with higher levels of adiposity being associated with less cognitive change," the authors write. "Traditional metabolic factors, adipocytokines [compounds produced by fat tissue] and sex hormones do not explain this sex difference. Future studies should confirm these longitudinal associations with adiposity and cognitive change and investigate why adiposity has inverse associations in men and women."

Obese Middle-Aged Adults and Underweight Older Adults Appear to Have Increased Risk for Dementia

Midlife obesity may be associated with risk for dementia, but after age 65, the relationship between body mass index and dementia appears to reverse so that underweight individuals are at higher risk. Annette L. Fitzpatrick, Ph.D., of the University of Washington, Seattle, and colleagues analyzed data from 2,798 adults (average age 74.7) without dementia. Participants reported their weight at age 50 (midlife) and had their height and weight measured at age 65 or older (late life).

Over an average of 5.4 years of follow-up, 480 individuals developed dementia, including 245 with Alzheimer's disease and 213 with vascular dementia. In evaluations of midlife obesity, individuals with a body mass index (BMI) of higher than 30—classified as obese—were more likely than those of a normal weight to develop dementia. However, those who were underweight (BMI of lower than 20) in late life had an increased risk of dementia, whereas being overweight in late life was not associated with dementia and being obese appeared to have a protective effect.

"The greatest dementia risk was found in underweight individuals at older ages. These findings suggest the predictive ability of BMI changes across time," the authors write. "These results help explain the 'obesity paradox' as differences in dementia risk across time are consistent with physical changes in the trajectory toward disability."

Heart Disease Risk Factors Associated With Faster Cognitive Decline

Individuals with higher total and low-density lipoprotein (LDL, or "bad") cholesterol levels and a history of diabetes appear to experience a more rapid cognitive decline after developing Alzheimer's disease. Elizabeth P. Helzner, Ph.D, and colleagues at the Columbia University Medical Center, New York, studied 156 patients who were diagnosed with Alzheimer's disease at an average age of 83.

During an average of 3.5 years of follow-up, those who had higher LDL and total cholesterol levels before diagnosis experienced a more rapid decline on cognitive test scores than those whose cholesterol levels were in the normal range, as did those with a history of diabetes when compared with those without diabetes.

The study "provides further evidence for the role of vascular risk factors in the course of Alzheimer's disease," the authors conclude. "Prevention or treatment of these conditions can potentially slow the course of Alzheimer's disease."

Review: Insulin Resistance May Links Metabolic and Cognitive Disorders

Insulin resistance, when tissues in the body lose sensitivity to the hormone that regulates glucose, may underlie both dementia and metabolic disorders such as obesity and diabetes. In a review article, Suzanne Craft, Ph.D., of Veterans Administration Puget Sound Health Care System and University of Washington School of Medicine, Seattle, writes that "considerable progress has been made in establishing relationships among metabolic disorders and late-life dementing illnesses," including through the common foundation of insulin resistance.

"A number of challenges must be addressed as we move forward to determine the key mechanisms underlying these associations," Dr. Craft concludes, including establishing clear definitions of both metabolic and neurological conditions. "Future research aimed at identifying mechanisms that underlie comorbid associations will not only provide important insights into the causes and interdependencies of late-life dementias, but will also inspire novel strategies for treating and preventing these disorders."

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Journal References:

  1. Yaffe et al. The Metabolic Syndrome and Development of Cognitive Impairment Among Older Women. Archives of Neurology, 2009; 66 (3): 324 DOI: 10.1001/archneurol.2008.566
  2. Kanaya et al. Total and Regional Adiposity and Cognitive Change in Older Adults: The Health, Aging and Body Composition (ABC) Study. Archives of Neurology, 2009; 66 (3): 329 DOI: 10.1001/archneurol.2008.570
  3. Fitzpatrick et al. Midlife and Late-Life Obesity and the Risk of Dementia: Cardiovascular Health Study. Archives of Neurology, 2009; 66 (3): 336 DOI: 10.1001/archneurol.2008.582
  4. Helzner et al. Contribution of Vascular Risk Factors to the Progression in Alzheimer Disease. Archives of Neurology, 2009; 66 (3): 343 DOI: 10.1001/archneur.66.3.343
  5. Craft et al. The Role of Metabolic Disorders in Alzheimer Disease and Vascular Dementia: Two Roads Converged. Archives of Neurology, 2009; 66 (3): 300 DOI: 10.1001/archneurol.2009.27

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JAMA and Archives Journals. "Metabolic And Neurological Disorders May Share Common Risk Factors." ScienceDaily. ScienceDaily, 15 March 2009. <>.
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