Scientists are pushing the boundaries of their search to find a cure (or cause) of Alzheimer’s disease to include identifying the key risk factors for the disease. The effort could make a significant difference to the number of new cases, which is set to rise to more than 130 million by 2050. The evidence is building that vascular risk factors are associated with the onset of Alzheimer’s and the metabolic diseases that affect it, like diabetes, are getting more attention. The incidence of Type 2 diabetes has quadrupled since 1980, and it now affects over 422 million people worldwide. New research is looking at how it affects brain health and the risk of dementia. We spoke to Rachel Whitmer, an epidemiologist at the Kaiser Permanente Northern California Division of Research who studies populations over time to identify risk factors for Alzheimer’s disease. She focuses on diabetes to try figure out ways that people with the disease can lower their risk of dementia.
Being Patient: What is the link between diabetes and dementia?
Rachel Whitmer: We know that people with diabetes have about 75-100 percent higher risk of dementia. Most people with diabetes are Type 2 and Type 2 is going up enormously because of the obesity epidemic. One thing that’s not known for this group is what’s best for the brain – that’s uncharted territory. We have longitudinal information on patients with diabetes from the Kaiser Permanente Diabetes registry, so we’ve learned over time that, for people with Type 2 diabetes, things that elevate your risk are core glycemic control – if you’ve had a very acute high blood sugar or low blood sugar episode that puts you at higher risk. We know that depression is a large risk factor for dementia in people with Type 2 diabetes and we know that the more vascular complications you have also elevates your risk.
I think the new frontier that’s not known so well is older people with Type 1 diabetes because that’s very different from Type 2. Type 1 is a smaller group but it’s going up in incidence as well and we don’t quite know why. It tends to be a younger age of onset. You’re on continual insulin and you have to be extraordinarily vigilant about your treatment from the beginning. We still need to understand for these people whether they’re at an increased risk of dementia and what affects their cognitive function.
Being Patient: Do we know how diabetes affects the brain?
Rachel Whitmer: We can’t tell you what the mechanism is with the big population-based studies that we do but people who are doing molecular and biochemistry work are zooming in on this. The next step [for us] is to closely follow these people’s cognitive function and do brain imaging. There are a lot of different theories about what’s happening. There was a lot of work 8-10 years ago on the insulin degrading enzyme which is produced in the brain and it’s thought that it may play a role in amyloid beta deposition, one of the components of Alzheimer’s disease. There are other theories that say that Alzheimer’s is an insulin resistant brain state. I’m not saying I believe that necessarily but there’s so much we still don’t know about the brain.
Being Patient: If you have diabetes, what can you do to lower your risk?
Rachel Whitmer: You need to have appropriate glycemic control and you need to try to avoid complications. The advice is the same as you’d give someone without diabetes. What’s good for the heart is good for the brain so you need to look at vascular risk factor control and have an active lifestyle. Depression over the life course is also associated with a higher risk of dementia. In the lifestyle intervention trials that have been done so far, one of the things that hasn’t been done is depression treatment, and I think that’s an exciting avenue of future work. I think it’s very tricky because if you’re looking at depression late in life you’re looking at people with early dementia and it’s something that you probably want to start earlier.
Being Patient: What about obesity? Do scientists understand why it could be a risk factor for dementia?
Rachel Whitmer: The obesity story is very complicated. What’s consistent is that obesity in mid-life is a risk factor but things don’t look the same when you look in late life. It’s not that it’s not bad – it’s just that people who are obese who make it to late life are very selective so it’s hard to draw conclusions from that. There’s also evidence that some of the changes in the brain that happen with dementia could affect weight loss so if you’re looking late in life it might not be an accurate picture. There are also plenty of thin fit people who get Alzheimer’s and dementia.
Being Patient: Have you identified any risk factors in early life?
Rachel Whitmer: It’s a new area of research for Alzheimer’s and dementia but it speaks to the fact that you need to think about brain health over the lifespan. We conducted a study recently that found that being born in states [in the U.S.] with really high infant mortality rates was a risk factor for dementia, particularly for African-Americans. Even though all of the people [in the study] subsequently moved to California. [High infant mortality] is a proxy measure for an adverse environment and it really points to the idea that a short term exposure to that could possibly affect the brain’s ability to handle a disease and the point at which a person shows cognitive decline. At the time that someone shows symptoms of dementia or cognitive impairment, they have different degrees of pathology, so people have varying thresholds for what they can handle before they are showing signs. Our hypothesis is that that is what the findings of the study were about.