White Matter Disease
by Mind Over Matter V 13:
Take Steps to Protect the Small Vessels in Your Brain
As people age, it is common for abnormalities to appear in the white matter of their brains, and for those changes to get progressively worse over time, particularly after midlife. These abnormalities appear on different types of brain scans and are referred to by a variety of terms, including white matter hyperintensities, leukoaraiosis, white matter lesions, and white matter disease.
White matter hyperintensities (WMHs) are present to some degree in the brains of most individuals aged 60 and over, with prevalence increasing with age until an estimated 95% to 100% of those aged 80 and over show some degree of WMHs. Not only does the prevalence of WMHs increase with age, but so does the severity (i.e., the amount of WMHs present).
WHILE THE PRESENCE OF WHITE MATTER ABNORMALITIES IS COMMON AND WAS ONCE CONSIDERED A TYPICAL PART OF BRAIN AGING, THERE IS GROWING EVIDENCE THAT THESE ARE NOT BENIGN CHANGES.
For many people, WMHs appear in their brain scans yet they have no noticeable symptoms, at least initially. Over time, though, as the volume of WMHs grows, that often changes. WMHs have been linked to a variety of negative impacts, including:
· cognitive impairment and dementia;
· functional impairment – i.e., declining ability to perform activities of daily living (ADL) independently;
· walking and balance problems;
· increased risk of stroke, worse stroke severity, and worse short- and long-term post-stroke outcomes; and
· depression.
WHAT CAUSES THESE AGE-RELATED ABNORMALITIES IN WHITE MATTER?
Although a variety of conditions can potentially lead to abnormalities in the white matter of aging brains, a common cause is cerebral small vessel disease – an umbrella term used to describe various abnormalities related to the brain’s small blood vessels.
Deep white matter areas of the brain lie at the ends of the arterial circulation system, where the smallest of arteries are found. These small arteries are particularly susceptible to decreased blood flow and oxygenation, which is often caused by atherosclerosis (a buildup of plaque on the artery walls).
As plaque increases in the arteries, they become narrower, potentially leading to a stroke from blocked blood flow (ischemic stroke) or a burst artery (hemorrhagic stroke). Yet, white matter abnormalities are observed in the brains of people who have not had an ischemic or hemorrhagic stroke.
One possible explanation for this occurrence is multiple “silent” strokes (i.e., mini, symptomless strokes). Dr. Daniel Mandell and colleagues conducted a study investigating that possibility and shared their findings in Annals of Neurology in October 2014. The researchers looked at brain scans from five adults with leukoaraiosis, taken over a 16-week period.
The participants ranged in age from 57 to 79 and had moderate to severe abnormalities in their white matter and no evidence of previous strokes at the commencement of the study. A magnetic resonance imaging (MRI) scan of each participant’s brain was taken each week throughout the study, allowing the researchers to observe subtle changes over time.
The brain scans revealed evidence of tiny strokes appearing in the white matter of most participants over time, yet the participants did not experience any symptoms. When these tiny strokes were new, they were visible on the MRI scan, but ultimately became indistinguishable from the existing white matter disease. These findings suggest that repeated tiny silent strokes are a cause
of leukoaraiosis.
“By studying participants’ brains each week, we were able to identify the presence of tiny, symptomless strokes. If we had only conducted MRIs at the beginning and end of the study, instead of every week, we would not have been able to tell that these strokes had happened, because they are so small and eventually just blend in with the existing leukoaraiosis,” said Dr. Mandell, an Associate Professor at the University of Toronto.
“WE SUSPECT THAT EACH TINY STROKE IS SO SMALL IT ONLY HAS A MINOR IMPACT ON BRAIN FUNCTION, SO MINOR THAT IT IS NOT NOTICEABLE. BUT AS PEOPLE HAVE NUMEROUS TINY STROKES OVER TIME, THE DAMAGE ACCUMULATES UNTIL THERE IS SUFFICIENT QUANTITY FOR SYMPTOMS TO APPEAR, AT WHICH TIME THE PERSON MAY BE WELL ALONG THE PATH OF DEVELOPING DEMENTIA.”
Dr. Mandell and his team are currently engaged in phase two of this study – this time using a new technique known as a super-resolution MRI scan, which can detect much smaller silent strokes. The researchers will first identify which study participants are showing signs of active micro-strokes during ten consecutive weeks of scans, and then see whether those who experienced active injuries during that initial period go on to develop worsening white matter disease and declining cognitive performance (during follow-up scans one and two years later).
“So far we’ve worked with five participants in this phase two study, and we’re seeing smaller silent strokes than ever before,” said Dr. Mandell. “These early results are promising, suggesting a potential future screening tool. I believe it may be possible to use a single scan with this very high resolution to identify who has active disease in the small vessels of their brain, thereby helping with early identification of people at high risk of later cognitive decline.”
WHITE MATTER DISEASE CAN HAVE WIDESPREAD COGNITIVE EFFECTS
Dr. Brandon Vasquez and a colleague conducted a meta-analysis to examine the impacts of white matter disease on various cognitive functions. They reviewed cognitive performance scores for more than 2,500 people across 27 research studies. Nearly 800 of these individuals had been diagnosed with cognitive impairment due to a vascular cause (i.e., white matter disease) but not serious enough to compromise daily life function, and the rest were healthy controls. Their findings were published in the Journal of Neuropsychology in March 2015.
Compared to the healthy controls, the participants with vascular cognitive impairment showed weaknesses in all eight cognitive domains that were measured: namely, executive functioning, thinking speed, general functioning, language, immediate memory, delayed memory, working memory, and visuo-spatial construction. Thinking speed showed the greatest impairment, followed by immediate and delayed memory. Working memory and visuo-spatial abilities were the least affected.
“Our findings expand on the growing body of evidence about the impacts of white matter disease on cognitive function by showing that a large number of areas are affected, more than previously thought,” said Dr. Vasquez, a Clinical Neuropsychologist at Baycrest Health Sciences in Toronto.
“WHITE MATTER DISEASE APPEARS TO BE A DISCREET SABOTEUR IN THE BRAIN WITH WIDESPREAD NEGATIVE IMPACT ON COGNITIVE FUNCTION.”
THE ROLE OF WHITE MATTER CHANGES IN ALZHEIMER’S DISEASE
Accumulating evidence from brain scan studies suggests that cerebral small vessel disease (appearing as higher WMH volume on MRI scans) is linked with the risk and progression of Alzheimer’s disease (AD). Researchers previously believed that WMHs played an additive role in AD, contributing to the symptoms experienced but not being a core feature of the disease.
More recently, however, researchers are considering the possibility that WMHs (along with AD's hallmark plaques and tangles in the brain) may play a key role in the clinical manifestation of the disease. Plaques and tangles rarely exist in isolation (i.e., without evidence of cerebrovascular disease being present as well).
An estimated 30% of older adults have elevated amyloid-beta levels without any symptoms of AD. Additionally, the amount of amyloid-beta present in the brain is only weakly correlated with the severity of AD symptoms. In other words, having higher levels of amyloid-beta does not always mean that a person will have worse symptoms. Dr. Adam Brickman, a Professor of Neuropsychology at Columbia University in New York, noted that
“ALZHEIMER’S DISEASE HAS LONG BEEN ASSOCIATED WITH AMYLOID-BETA PLAQUES AND TAU TANGLES. HOWEVER, RESEARCH CONDUCTED BY MY TEAM AND OTHERS SUGGESTS THAT WHITE MATTER ABNORMALITIES LIKELY PLAY A KEY ROLE IN ALZHEIMER’S DISEASE, TOO.”
“While amyloid-beta is a defining pathological feature of Alzheimer’s disease, it is not enough on its own to cause Alzheimer’s-related symptoms. The presence of white matter hyperintensities, likely caused by cerebral small vessel disease, may contribute to clinical symptoms of Alzheimer’s disease in a synergistic way to the effects of amyloid-beta," he continued.
"Or, it may be a primary factor, all on its own, in the development of the Alzheimer’s disease clinical syndrome. This area of research is exciting because much is already known about how to treat and prevent vascular disease, including cerebral small vessel disease. So, perhaps by taking steps to intervene on vascular disease, we could mitigate the symptoms of Alzheimer’s disease.”
TREATMENT & PREVENTION OF CEREBRAL SMALL VESSEL DISEASE
The general approach to preventing or treating cerebral small vessel disease is to address any underlying vascular risk factors, such as high blood pressure, high cholesterol, high blood sugar, and smoking. This can mean making lifestyle changes like quitting smoking, engaging in regular exercise, adopting a healthy diet, getting enough sleep, and taking steps to reduce stress. It might also involve taking medications prescribed by your doctor to address high blood pressure, high cholesterol, or diabetes.
WHAT’S HEALTHY FOR YOUR HEART IS WHAT’S HEALTHY FOR YOUR BRAIN.
By taking proactive measures to help prevent heart attack and stroke, you may also help prevent, delay, or slow cognitive decline, Alzheimer’s disease, and more. And, the sooner you do so, the better. “White matter hyperintensities tend to accumulate in the brain gradually over time. This suggests that preventative steps will likely be most effective if they are taken starting in midlife or earlier,” said Dr. Brickman.