■ When the elderly decline mentally—they complain of slowing down or lose interest in their bridge club, for example—family, friends and even their doctors may blame it on the natural effects of aging. Indeed, many of the most common ailments of the elderly are written off as signs of getting old, including urinary incontinence, poor balance, depression, apathy and confusion. But new studies suggest that the true cause of some age-related changes in mood may be so-called silent strokes: tiny blockages of blood vessels deep inside the brain which cause real damage but don’t show obvious symptoms, such as muscle paralysis or garbled speech. In addition, imaging studies of people who have had silent strokes are giving us valuable new insights into the workings of the brain’s mood and memory circuits.
__ How can someone have a stroke and not notice? If you’ve never heard the term silent stroke, you aren’t alone; scientists are just beginning to realize their importance. Although the term silent is a bit of a misnomer, they are called silent because the regions of the brain that are most likely to suffer these kinds of strokes may not cause much change in a person’s motor functions, speech, pain, or sense of touch. They are involved more with thinking and mood regulation—and thus harder to detect. Hence, strokes in these regions of the brain are referred to as silent. Silent strokes mostly happen in parts of the brain that are dependent on single, tiny blood vessels for their supply of oxygen and nutrients.
__ These regions, such as the frontal cortex and the deep white-matter tracts crisscrossing inside, lack alternative supply lines, called collaterals, if the tiny vessel is blocked. People who are otherwise healthy don’t usually assume they may have had a little stroke while they were asleep or driving, even if they experience subtle emotional changes. As a result, millions of people are literally walking around without knowing they’ve have had a stroke. They usually attribute changes in their mood or memory to something else, such as age, fatigue, or a recent social event. Many elderly people live alone, suffer from multiple medical conditions, and have faced personal losses—so new signs of depression can often be mistaken as a normal reaction and dismissed.
__ Globally, about 10% of healthy middle-aged people are thought to have had silent strokes without being aware of it. And silent strokes are nearly five times more common than regular strokes. In the United States alone, each year some 11 million people are estimated to have endured a silent stroke—a shockingly large number. In a population study called the Cardiovascular Health Study, 3,660 adults, in their 60s and older, underwent MRI scans of their brains. Of these, 31% showed evidence of a stroke—yet most denied ever having had one. The symptoms, when present, were often vague; not even their doctors attributed them to a stroke. Are these a new phenomenon? Not at all. Doctors have long noted such findings postmortem. What is new is that, with the greater availability of higher-resolution brain MRI scans, more of these strokes are being detected in living individuals.
Silent but Hardly Benign
While these little strokes may not cause major paralysis, they do produce more subtle symptoms—ones we usually attribute to normal aging and may not link to brain damage due to a stroke. Impairment of a person’s balance leading to more falls, loss of bladder control causing urine leakage, changes in mood and personality, and the loss of cognitive abilities are some of the common symptoms associated with silent strokes. Silent strokes can also increase the probability of more serious strokes in the future, and eventually death. Depression is a telling example.
__ Studies conducted by our group at Duke University in the 1990s found that older adults who experienced depression for the first time in their older years were more likely to display evidence of silent strokes on brain MRI scans than an age-matched control group who did not have depression. The term vascular depression was coined to describe such individuals. At that time, depression in older adults was generally being attributed to life changes, such as loss of a loved one or retirement. Studies conducted at Duke and Cornell universities (among others) also found that such individuals are more likely to respond poorly to antidepressant medications and are at greater risk for having recurrent depressive episodes and functioning less well in daily activities. People with vascular depression also tend to be more impaired in their attention, information-processing speed and memory, all of which can put them at greater risk for developing dementia. Indeed, vascular causes are the second most common cause of dementia (vascular dementia) globally, which is a tragedy since many of these cases are probably preventable with early detection and risk-modification. (More on that below.)
Imaging studies of patients with vascular depression who have had silent strokes often reveal quite a lot about the brain circuits involved in such emotions as sadness, apathy and euphoria. Many initial studies suggested that strokes in the left side of the brain appeared to be more often linked with sadness, whereas those in the right side of the brain were linked with euphoria/mania. However, a systematic review of over 40 studies raised doubts about this laterality theory. More recently, silent strokes in a specific region in the front underside of the brain, the medial orbital prefrontal cortex, have been linked to depression, suggesting that this region might be a key relay station in the brain’s mood circuit. Other brain regions where silent strokes could result in depression include the basal ganglia, amygdala and frontal white matter. A study using functional MRI (a novel type of MRI that can take pictures of the brain in action) found that silent strokes can affect a specific brain network called the default network, which is involved in such cognitive processes as memory and attention.
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 (e.g., 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. bw
Dr. 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. Dr. Doraiswamy is Professor and Director of the Mental Fitness Lab in the department of psychiatry at Duke University, and is co-author of The Alzheimer’s Action Plan, an acclaimed consumer guide to memory problems.