A single episode of low blood sugar severe enough to require prompt medical attention increases a person’s risk of developing dementia in old age, a study in people with diabetes suggests. More than one bout of hypoglycemia seems to heighten the risk even further, researchers report in the April 15 Journal of the American Medical Association.

While chronically high blood sugar is known to increase the risk of dementia and other health problems, less is understood about the long-term effects of periodic low blood sugar, says study coauthor Rachel Whitmer, an epidemiologist at the Kaiser Permanente Division of Research, in Oakland, Calif.

She and her colleagues analyzed medical records from a Kaiser Permanente registry dating from 1980 to 2002 and identified nearly 17,000 people who had type 2 diabetes but no signs of dementia, mild cognitive impairment or even memory complaints during the time span. The people averaged 65 years of age as of 1994.

The scientists noted any low blood sugar episodes that required a trip to a hospital or other emergency facility. For such treatment, Whitmer says, a patient would have gone beyond just being shaky and weak, as happens with mildly low blood sugar. “These were events where patients may have fainted or passed out or may have been unable to communicate with others — and were brought in,” she says.

The scientists then checked for any dementia diagnoses from 2003 to 2007 in this population and found 1,822 cases.

After accounting for differences in age, weight, race, education, gender and diabetes history, the researchers found that people with one severe low blood sugar episode on their record were 45 percent more likely to have dementia in their later years than were people without any blood sugar crashes on their charts. Those with two or more episodes faced more than double the risk of dementia.

Because the study is observational, it’s not clear whether severe low blood sugar actually contributes directly to dementia risk or whether some people already had unnoticed cognitive impairments that heightened their risk of a blood sugar drop — possibly by mishandling medication, Whitmer says.

But when she and her colleagues looked at data only from the early 1980s — nearly two decades before any dementia diagnosis, and when patients were younger and would have been less likely to have dementia — they found that low blood sugar episodes back then still correlated with slightly higher dementia risk later.

The authors hypothesize that a glucose shortage in brain cells or other biomechanisms might play a role.

“This is a worrisome association,” says endocrinologist Philip Cryer of Washington University in St. Louis. But he cautions that an association doesn’t prove that one factor causes the other. “I wouldn’t want doctors and patients to overreact to this hypoglycemia issue and leave blood sugar levels to run high,” Cryer says.

Type 2 diabetes cases worldwide have risen sevenfold since 1983, says physician David Nathan of Harvard Medical School and Massachusetts General Hospital in Boston, writing in the same JAMA issue. This and other recent studies show that “despite the strides that have been and continue to be made, optimal care of patients with diabetes remains an elusive, albeit critical, goal,” he says.

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