October 4, 2017
Nearly half of dementia cases are triggered, at least in part, by vascular disease, which causes a decrease in the blood supply to neurons in the brain. Scientists are still working out the complex relationship between neurodegeneration and a breakdown in the blood vessels. We asked Dr. Francesca Fang-Liao, Ph.D., Professor of Pharmacology at the University of Tennessee, about what her research into the vascular system in the brain is revealing about the cause of dementia and how it can be stopped.
- Cerebral small vessel disease, the narrowing of the tiny blood vessels supplying the neurons in the brain, could be a main cause of nerve cell death
- Dr. Fang-Liao is trying to find new drug targets for dementia by examining vascular disease in mice
- Lowering your risk of heart disease and stroke can help to prevent dementia
Being Patient: Why should Alzheimer’s researchers pay attention to metabolic disorders and vascular disease?
Dr. Fang-Liao: Most researchers in the last two decades have focussed on figuring out how to stop the accumulation of beta-amyloid plaque and tau protein tangles in the brain. But there’s a lot of evidence showing that there’s a tight link between vascular disease in the brain and the onset of dementia because of reduced blood flow. The majority of stroke patients develop dementia or experience cognitive decline because their blood supply to the brain has been reduced. But stroke patients are only a fraction of the people that develop vascular dementia. For most people it’s the so-called ‘silent’ cerebral small vessel disease where tiny microinfarcts [tiny strokes that occur in the blood vessels of the brain] cause brain damage, which leads to dementia.
This could be the biggest risk factor for Alzheimer’s and vascular dementia. But it can be a very insidious process that happens over a decade, or maybe even several decades, before there are any clinical signs of cognitive decline. We haven’t been able to investigate what’s really occurring in the brain. It is now receiving a lot of attention in the field but people just don’t know how to study it because we don’t have an appropriate animal model.
Being Patient: How is your research addressing that?
Dr. Fang-Liao: If you look at a typical aging population in a nursing home, they usually have more than one disease. Many of these are metabolic disorders like hyperglycemia, which means high glucose, like a diabetic condition. Or, they have a poor heart and very high cholesterol and they are usually taking a lot of medications. And then, of course, in general, their health condition is just poor. These are the people who have the highest incidence of developing dementia. Most of the mouse models that are used have a very rare genetic form of the Alzheimer’s, so they’re not representative of a typical case of the disease. A pre-symptomatic dementia patient can have hypoperfusion [decreased blood flow] and it could be decades before they show any other pathology, like the build up of beta amyloid or tau.
My research is developing a mouse model for the study of small vessel disease. We have mice that display the most representative vascular risk factors, such as hypoperfusion [reduced blood flow in the blood vessels], and see how it can progress into dementia. Through studying these mice we could identify new targets for drugs for the treatment of dementia.
Being Patient: What developments have you seen in the field of research in response to this new evidence on the role of vascular disease in dementia?
Dr. Fang-Liao: We’re seeing the paradigm shifting in research in the dementia field. More attention is being paid to small vessel disease and scientists are shifting their attention to assessing the risk in middle-aged populations, aged 40 to 60. This is a group at the peak of their careers, who have family duties and a huge stress burden. Stress is an important factor in the development of disease and our genetic predisposition is also important. My whole family on my father’s side all got hypertension, including me, which reduces blood flow to the brain. So all of my research is driven by my own body. I’m racing against the advancement of my own medical condition.
Being Patient: What does this mean for people who are at risk of developing dementia or vascular disease?
Dr. Fang-Liao: The good news is that there are a lot of very effective drugs for regulating metabolic disorders and vascular disease risk factors like cholesterol and glucose levels and heart disease. If people get their blood glucose level and their cholesterol controlled, that should help to prevent or slow down the progression of dementia.
It’s also important to pay attention to lifestyle choices. There’s a lot of research on how eating a diet with good fats, omega-3 and -6, can help to soften blood vessels and prevent hardening, preserving good blood circulation. Combine that with ten thousand steps a day if that’s are feasible. That’s a very effective way for someone to control their entire metabolic profile. That’s the best thing to do instead of waiting for a new drug. When I turned 50, I started dancing Tango. Last year my triglyceride level was 700. [Triglycerides are fatty acids stored in the body. At high levels they may increase the risk of heart disease.] Three months after I went back to dancing, it dropped to a normal level of 100 and I’ve maintained that until now, so it’s never too late.