Treating metabolic disorders may aid neurologic health

Researchers are investigating previously noted connections between metabolic and neurologic disorders. By doing so, they are identifying possible ways to delay the onset of such diseases as Alzheimer's and other dementias, or at least slow their progress.

For instance, because evidence suggests diabetes increases the risk of Alzheimer's disease and vascular dementia, good blood glucose control could serve to hold off the serious neurologic conditions, according to research in the March Archives of Neurology.

The theme issue on neurological disorders related to metabolic diseases contains several studies that cover links between cognitive decline and metabolic syndrome in women, extra pounds in older men, and an accumulation of heart disease risk factors and insulin resistance in older men and women.

The nation's aging population virtually guarantees the number of people with Alzheimer's will climb. During the next 50 years, the disease's incidence and prevalence, as well as other forms of dementia, are expected to double among people ages 75 to 85 and quadruple in those older than 85, write researchers from the University of California, San Francisco, in the Archives.

Metabolic syndrome and diabetes also are on the increase due to the nation's obesity epidemic. But while physicians and their patients can take action to lower weight, control blood pressure and cholesterol, and keep blood glucose levels in check, treatments for Alzheimer's disease remain largely out of reach.

One study in the Archives found a history of diabetes and elevated levels of cholesterol, especially LDL cholesterol, are associated with faster cognitive decline in patients with Alzheimer's disease.

"These findings indicate that controlling vascular conditions may be one way to delay the course of Alzheimer's, which would be a major development in the treatment of this devastating disease as currently there are few treatments available to slow its progression," said Yaakov Stern, PhD, senior author of the report and director of the Cognitive Neuroscience Division of the Gertrude H. Sergievsky Center at Columbia University Medical Center in New York City. Stern's study followed 156 men and women in a New York community for as long as 10 years to chart their progress in such tasks as memory, abstract reasoning and language.

The links go on

A second study in the same issue found older women with metabolic syndrome had a 66% age-adjusted increased risk of developing cognitive impairment compared with women who did not have the syndrome.

The team of researchers defined metabolic syndrome as having three or more of the following five symptoms: abdominal obesity, elevated blood triglycerides, reduced HDL cholesterol, elevated blood pressure and type 2 diabetes.

"This means it is important for older patients with metabolic syndrome to be screened early for cognitive impairment, and that the component symptoms of the syndrome should be treated early," said lead author Kristine Yaffe, MD, professor in residence at the University of California, San Francisco's departments of psychiatry, neurology, epidemiology and biostatistics.

Co-author Andrea Weston, MPH, staff research associate for the UCSF Dept. of Psychiatry, noted it was, in general, the syndrome as a whole that made the difference rather than each component. "Except for high blood glucose, no one individual component was associated with higher risk of cognitive impairment in these women."

The nearly 5,000 women in the study were enrollees in a multicenter, multicountry trial testing the effects of an osteoporosis drug on vertebral fractures. Of the nearly 500 women in the study who had metabolic syndrome, 7.2% developed cognitive impairment. Among those without metabolic syndrome, 4.1% became cognitively impaired. The study was funded in part by Eli Lilly and Company, which manufactures diabetes and osteoporosis drugs.

Some other surprising results were included in the Archives issue. For example, a third study found that excess fat in older adults resulted in cognitive decline only among men. The researchers studied more than 3,000 men and women ages 70 to 79 and measured their fat levels by assessing body mass index; waist circumference; sagittal diameter, or the distance between the back and the highest point of the abdomen; total body mass measured by whole body DEXA scan; and visceral fat as measured by CT scan.

"I thought we would see a uniform association for men and women," said lead author Alka M. Kanaya, MD, assistant professor of medicine, epidemiology and biostatistics at the University of California, San Francisco. However, she noted the finding is not unique and has been seen before; for example, in the Framingham Heart Study, where higher BMI predicted worsening cognition in men alone.

"The overall message should be to maintain a healthy weight throughout life. It may be that fluctuations in weight are unhealthy," said Dr. Kanaya.

She cautioned that weight loss shouldn't be emphasized among older women. "I don't think there is any evidence that supports that for improving cognitive outcomes."

Dr. Kanaya believes a solid connection exists between metabolic and cognitive disorders, "but I don't think anyone can tell you for certain why."

The theme of neurological disorders and their relationship to metabolic diseases will be continued in other AMA Archives journals this spring as well as the April 15 Journal of the American Medical Association, which is a theme issue on diabetes.