Pinpointing Causes, Cautiously
Silent strokes can happen when there is a blockage or when a blood vessel bursts. Factors we cannot control, such as old age and genetics, as well as many we can, such as smoking, high blood pressure, high cholesterol, obesity, diabetes, and heart attacks, increase the risk of blocking the blood supply by narrowing the blood vessels to the brain or creating clots. Bleeding into the brain can happen if someone has an inherited bleeding disorder, is taking blood thinners, such as aspirin, or has a weakness in the vessel wall, such as an aneurysm, that bursts.
In one study conducted in the Netherlands, middle-aged adults who had aortic calcifications on abdominal x-rays (a sign of vascular disease) were more likely to suffer a silent stroke 20 years later. Another study of identical elderly male twins showed the most significant determinants for silent stroke were: higher levels of blood sugar, HDL cholesterol (typically considered the “good” cholesterol), and systolic blood pressure. These studies suggest that midlife (40s–60s) cardiovascular risk factors play an important role in determining risk for silent stroke in older ages. Thus, what’s good for your heart is good also for reducing the risk for silent strokes.
Good Genes, Bad Genes
Occasionally, inherited genetic mutations can lead to silent strokes. The most common such condition is CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy), where a gene mutation leads to a weakening of the blood-vessel wall and mini-strokes in a person’s 40s and 50s. These are usually diagnosed using MRI scans. People with this condition also have migraine headaches. Another chemical system, called the renin-angiotensin system, regulates the body’s blood pressure and water balance. Variations of the genes coding for the angiotensin receptors have also been related to progression of silent strokes.
Thus, there are probably dozens — and perhaps thousands — of different genes that might raise one’s risk for strokes. Likewise, there are also dozens of genes that affect risk for depression or memory impairment. Scientists are trying to study the interaction between all of these genes to identify the ones that raise the risk for vascular depression.
Not only are there risk genes, but there are also genes that protect us from strokes — people who have these are the genetic lottery winners. One example is a variant of a gene that causes the brain to produce more brain-derived neurotrophic factor (BDNF), which protects nerve cells. Rodent studies suggest that BDNF prevents brain damage when there is a reduction of blood flow in the brain, which is what typically occurs during a silent stroke. BDNF does not prevent the stroke itself, but acts as a shield.
In contrast, people who have another variant of the same gene (the lottery losers) called Val66Met are much more vulnerable to the effects of a stroke and suffer greater brain damage. This shows that variations of a single gene, called polymorphisms, can have opposite effects.
Thus, genetics may influence not only one’s risk but also how much damage one’s brain suffers during a stroke. Scientists are conducting large-scale studies (termed Genome Wide Association Studies) to determine which genetic patterns are most closely related to the risk for stroke. Such studies might help us better screen individuals at risk in the future and intervene before they suffer a stroke.
From UBOs to Prevention
On the low-resolution brain scans available before the 1980s, researchers referred to what we now call silent strokes as “unidentified bright objects” (UBOs) — because they did not know what they represented. Science has advanced rapidly, and, with newer MRI scans, doctors can quickly spot when someone has had a silent stroke. We do not recommend that all people over 65 have a routine MRI to determine whether or not they have had a silent stroke, because it would not be cost-effective.
But clearly, if you have had recent changes in your mood or memory, and have risk factors such as diabetes or high blood pressure, then you should consult a doctor. Only a doctor can determine if you need a brain MRI or not, and there are many different types of tests and scans (for example, carotid ultrasound, Doppler, MR angiography, diffusion MRI) that can each be useful for evaluating silent strokes.
Also, it should be noted that vascular depression is still a research diagnosis that many general doctors may not have even heard of. There are still many things we need to learn about it. But now that we know the telltale signs of silent strokes, doctors are hoping we can identify people at risk sooner.
Silent strokes can be prevented if such individuals better control their risk factors. Watching one’s numbers (such as blood pressure, blood sugar, weight and blood cholesterol) to make sure they are in normal range, eating a heart-healthy diet, getting regular exercise, staying socially connected and involved, and getting annual physical exams to check on vascular risk factors, are the best ways one can reduce one’s risk for silent strokes and vascular depression.
K. Ranga Rama Krishnan is dean of the Duke-NUS Graduate School of Medicine in Singapore and director of the Conte Center for the Study of Late-Life Depression at Duke University. P. Murali Doraiswamy is director of the Mental Fitness Lab and professor in the department of psychiatry at Duke University and is co-author of “The Alzheimer’s Action Plan: The Experts’ Guide to the Best Diagnosis and Treatment for Memory Problems.”
This article was first published in Brain World Magazine’s Winter 2010 issue.
