CAA, Microbleeds and Dementia: An Update

Summary:  New research has increased our understanding of brain microbleeds and cerebral amyloid angiopathy (CAA).  However, we still don’t know how to prevent or treat these related conditions. 

Blood-thinning medications increase the risk of hemorrhagic strokes in people with microbleeds.  Unfortunately, there’s not yet enough data to develop guidelines for the use of blood thinners when microbleeds are present.

When my father died more than three years ago, his neurologist suspected that cerebral amyloid angiopathy (CAA) caused the microbleeds visible on his MRI as well as his dementia and hemorrhagic stroke.  Analyzing his brain tissue, researchers at Massachusetts General Hospital confirmed that he had “extensive” CAA.

This was fairly easy for me to understand: CAA deposits on the blood vessels in Dad’s brain caused the vessel walls to harden and crack, leading to bleeding, which caused damage to the brain, which caused dementia.  But new imaging technologies and recent research show the story was probably a bit more complicated.

Microbleeds and CAA:  More Common Than We Thought

The use of more sophisticated MRI scans has increased since Dad died, and these new scans have revealed that microbleeds are fairly common in older people.   An estimated 18 percent of 60-69 year olds have microbleeds, and that increases to 38% for those over 80.  But not all people with microbleeds have dementia.

Dad’s autopsy showed “moderate” Alzheimer’s pathology as well as CAA, and it now seems that’s very common.  According to one new study, more than 90 % of people diagnosed with Alzheimer’s have cerebral amyloid angiopathy.  CAA is also very common in people with Parkinson’s and dementia with Lewy bodies, and is strongly linked to cognitive decline in those disorders.

This new research has increased questions about the contribution of CAA to memory problems, and about its relationship to other pathologies.  Because CAA and Alzheimer’s often co-exist, and both involve beta amyloid protein, some researchers speculate they might share a common cause.  Scientists at the University of Southhampton in the UK, for example, have proposed that age-related hardening of blood vessels reduces the normal drainage of beta amyloid from the brain, and the protein then builds up as both CAA and Alzheimer’s plaques.

If You Have Microbleeds

So far, I don’t seem to have any of the microbleeds Dad had.  If I did, it’s not entirely clear what that would mean, especially since I don’t have significant memory loss.  “It’s true we don’t really know how to interpret the finding of a microbleed,” says Dr. Steve Greenberg, a neurologist and CAA specialist at Massachusetts General.  “Microbleeds don't perfectly correlate with cognitive impairment.”

If you have microbleeds, though, it’s important to know there are concerns about blood-thinners.  These medicines, used to treat high blood pressure and prevent ischemic strokes, may cause hemorrhagic strokes in people with microbleeds (the most well-known instance of this is Ariel Sharon, the former prime minister of Israel).

So should people with microbleeds take blood thinners?  “It's a really complicated decision for doctors,” says Dr. Greenberg, “with potential risks either way – that is, we might not give blood-thinning agents to people who will benefit from them, or we might prescribe them and cause a hemorrhage. This question is still in flux, awaiting more data.”

CAA Research Advances in the Lab

New research is improving our understanding of microbleeds and CAA.   It now looks like the microbleeds Dad had may not be the only mechanism by which CAA can cause problems.  A study by Dr. Greenberg and his colleagues at Massachusetts General suggests that CAA damages the structure of the small blood vessels in the brain, and this may independently contribute to dementia.

Work in other labs is adding to our knowledge.  A new University of Rochester study links increases in two proteins to CAA deposits, as well as to other pathologies associated with Alzheimer’s.  The authors of the Nature Cell Biology article about the study speculate that higher levels of the proteins might be triggered by insufficient oxygen to cells.  Researchers at the University of Toronto recently reported that certain immune cells may clear CAA deposits from blood vessels, at least in some genetically engineered mice.

Prevention and Treatment of CAA, Microbleeds and Hemorrhagic Stroke

Despite this progress, there are currently no treatments for CAA or for microbleeds, and any treatments based on this new research are years away.

It’s possible that proposed Alzheimer’s treatments aimed at clearing the beta amyloid associated with Alzheimer’s pathology could also be used to clear the beta amyloid involved in CAA.  So far, though, these treatments appear to increase, rather than decrease, the risk of microbleeds.   Research by Elan Pharmaceuticals shows that low doses of their proposed Alzheimer’s vaccine might reduce CAA in certain genetically engineered mice without the significant increase in microbleeds associated with higher doses.  It’s unclear how this might work in humans.

What about prevention?  Some scientists are convinced that improving diet and exercise, avoiding head injuries and reducing exposure to environmental toxins can reduce your risk of developing Alzheimer’s.  Could some of these factors also reduce the risk of CAA?  “I suspect the same measures that lower the risk for Alzheimer's may also lower the risk for CAA,” says Dr. Greenberg, “but we don't yet have evidence to support that.”

Brain imaging techniques continue to improve, making detection and tracking of microbleeds and even CAA deposits possible.  Dr. Wolff Kirsch and colleagues at Loma Linda University in California are testing “susceptibility weighted imaging” MRIs, which he believes are far more sensitive for detection of microbleeds than current techniques.  And Dr. Greenberg and his colleagues have shown that new imaging technology may allow researchers and doctors to detect and measure CAA in people’s brains.  Data gained from using more sophisticated imaging techniques, along with additional lab research, should move us closer to preventing and treating CAA, microbleeds and dementia.

Note:  This information is not a substitute for medical advice.  Please consult your doctors for information and treatment appropriate to your situation!

Comments

[Don Moyer]

I pointed a friend to one of your earlier posts. She said that you have a "very confortable style."

I agree: this post is an especially nice example of your "very comfortable style."

Your posts should be used as models in teaching science writing. Thanks. Don

[Mary Boomhower]

I was in an abusive marriage for thirteen years. We were divorced in 1981. I was diagnosed with dementia and a brain tumor three years ago!
I had brain surgery but the tumor was inaccesssible because it was buried under the massive are of dementia growth!!!

[Dolores Ferris]

My husband, aged 62, has been diagnosed with CAA following a seizure and collapse. This article has explained more to me in simple language than any other. Still trying to get my head around it all! Thank you.

[Deanna Galkiewicz]

My husband was recently diagnosed with probable CAA by way of incidental findings while preparing for an aortic aneurysm repair.(Cleveland Clinic) Because he is not symptomatic,i am having a difficult time finding any info on how quickly this disease can progress. I am understandably very upset. He has not grasped the potential seriousness of this diagnosis. He read a little the night before surgery, but has not mentioned it since. This did prove to be a wonderful opportunity to change his mechanical valve to a bovine. No more coumadin. Considering I can not find any info to substantiate a "glass half full" approach, I am not sure he necessarily needs to know. But I do!I am a nurse, have done extensive reading, compared his scans, MRI's to case studies on the web, all in an effort to find out when he will have a stroke or begin a slow downward road with dementia. He is 56 yrs old, we have an 11 yr old son.He has approx 20 microbleeds as of last week. I don't understand how he is not symptomatic. I know no one can give me a definitive answer, but I would like to know if 20 microbleeds at 56 yrs old is substantial. I know the neurologist will not discuss this with me unless my husband is present. I feel very alone. Thanks D

[Mona Johnson]

Deanna, I'm sorry to read about your husband, and I know how scary this must be for you. I'm not a healthcare professional, so can't really address what it means to have 20 microbleeds at 56 years old. I'm not sure that anyone can predict with certainty whether he'll develop symptoms.

I'm sure you want to address all the possibilities and take some action, and this must be incredibly frustrating for you.

I hope your husband is recovering nicely from surgery and that you are taking care of yourself.

[Roger Kulp]

This is indeed very scary.I'm just learning about this stuff.

My mother,age 80,has had several microbleeds,and may now be in the early stages of dementia.her sister, my aunt,died of an "alzheimer's like" diswase several years ago.

I have a lifelong history of anemia, a folate metabolism disorder,with multiple MTHFR nutations,as well as heart faiure,and "mysterious" cerebrovascular symtoms,starting in my teens,so there are all sorts of considerations here.