A little bit of memory loss is part of getting older. But a lot of memory loss, in the form of Alzheimer’s disease and dementia, can be completely debilitating. And there are ample indications that cognitive impairment in the form of memory problems and other difficulties is a growing problem: Some estimates indicate that cases of late-onset Alzheimer's, for example, may quadruple in the next three decades as the American population ages.
Researchers are beginning to look at diabetes—another fast-growing public-health problem—as a potential contributor to the phenomenon. "The whole gamut of diabetes and related conditions is connected to a wide range of cognitive impairment," says Columbia University epidemiologist José Luchsinger, MD, MPH. If people with diabetes may be more likely than others to suffer cognitive impairment as they age, Luchsinger says there's reason to believe that treating diabetes effectively may help stave off memory loss at the same time.
Cognitive impairment comes in two main varieties: vascular impairment and Alzheimer's disease. Vascular cognitive impairment is the result of damage to the blood vessels in the brain, the equivalent of tiny strokes that cause lapses in attention or problems in recalling information—"tip of the tongue" memory problems, in other words. Such cognitive impairment is one of various vascular problems that can accompany diabetes.
José Luchsinger, MD, MPH
Columbia University Medical Center
ADA Research Funding
Clinical Translational Research Award
Alzheimer's, on the other hand, is caused by the buildup of proteins called amyloids in the brain that leads to absolute memory loss. Some researchers have argued that the increasing insulin resistance that accompanies type 2 diabetes can make it harder for the body to clear away amyloids, making diabetes a contributing factor for Alzheimer's. "What's interesting about diabetes is there are plausible ways it could cause both vascular cognitive impairment and Alzheimer's, and everything in between," Luchsinger says.
The possibilities have made tracing the links between diabetes and memory problems even more important: If properly treating diabetes could also help stave off debilitating cognitive impairments, it would be a way to kill two birds with one stone. "We know [diabetes] can cause the vascular part, but there's also very compelling evidence that could link diabetes and insulin resistance to amyloid proteins," Luchsinger says. "It's possible that type 2 diabetes is causing cognitive impairments that affect quality of life all the way to full-blown dementia."
Luchsinger is looking for ways to test these links. "We're trying to establish what the mechanisms for these associations are and see in the context of clinical trials if these are true," he says. But such clinical trials are difficult.
To find out whether type 2 diabetes causes memory problems, you need to compare a large group of people with type 2 to a group without the disease over a long period of time. And you must try to do that in a way that eliminates other "confounders"—factors that could affect the results but have nothing to do with diabetes.
One tool Luchsinger uses is the Finnish Diabetes Prevention Study, an ambitious project begun in 1993. Finnish researchers recruited 522 people at high risk for type 2 diabetes and divided them into two groups. One group got standard care; the other was given an intensive course of diet and exercise education meant to change their lifestyle. "The results showed lifestyle intervention was very effective [in preventing diabetes] in this high-risk group of people," says Jaana Lindstrom, MSC, a researcher at the Finnish National Institute for Health and Welfare.
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With help from an American Diabetes Association grant, Luchsinger is using the Finnish study to look at the connections between diabetes and cognitive impairment. The idea is to see if people in the "intervention" group, many of whom are now in their 60s and 70s, performed better on memory and other cognition tests than counterparts who received standard treatment.
Working with his Finnish colleagues, Luchsinger is retesting more than 300 people involved in the original study, using a standard memory exam, to provide a baseline of data for future research. "The hope is to establish a long-term follow-up to see if intervention to prevent diabetes can result in benefits to cognition," Luchsinger says. "Sometimes you have to revisit how people are doing five to 10 years out to see if there are differences or not."
For her part, Lindstrom says that so far, patients from the original study are eager to take part; many of them are curious to see how their memory has fared over time. As this international team of researchers follows the original patients, it will be able to gather evidence on the connections between diabetes and Alzheimer's and other forms of cognitive impairment. The results may help doctors in the future treat both conditions more effectively.