Flash suggestion: An annual flu shot seems to be protective against cognitive decline. https://www.webmd.com/vaccines/news/20220630/flu-vaccine-older-minds-sharp-study

Flash suggestion: Research from Brazil suggests that eating processed food leads to a 25% faster cognitive decline compared to a diet without much processed food. https://www.nbcnews.com/health/health-news/highly-processed-food-linked-faster-cognitive-decline-rcna40999

Flash suggestion: Instead of the using the “Boston Criteria” to evaluate CAA, it may be worth applying “the simplified Edinburgh criteria” which are: -“high probability of CAA with lobar intracerebral hemorrhage with a subarachnoid hemorrhage on CT and finger-like projections from the intracerebral hemorrhage on CT;
–intermediate probability of CAA with intracerebral hemorrhage showing subarachnoid hemorrhage on CT in isolation;
– low probability of CAA with lobar intracerebral hemorrhage showing no subarachnoid hemorrhage.” https://radiopaedia.org/articles/edinburgh-criteria-for-lobar-intracerebral-haemorrhage-associated-with-cerebral-amyloid-angiopathy

Flash suggestion: Fasting, or intermittent fasting, can be a powerful means of slowing cognitive decline according to impressive research at USC. To facilitate fasting, however, the authors are promoting a product called ProLon, which–unfortunately–would be difficult for our site to evaluate. https://pubmed.ncbi.nlm.nih.gov/36170815/

Flash Suggestion. The CAA Forum has created an important new website with three separate sections oriented toward patients, clinicians, and researchers. It is being developed jointly by some of the best experts in the field, and it is definitely worth following. https://caaforum.org

Contents

• Cerebral Amyloid Angiopathy (CAA): Overview
• About this site:
• What you can do to get better–the importance of blood pressure, sleep, stress, exercise, a mediterranean diet
  • Things that are also worth considering:
• Some things to avoid: salt, aspirin, fish oil, blood thinners
• useful references (some are quite technical):
  • General references (non-technical)
  • Driving with Hemianopsia (Partial Visual Field Loss After Stroke)
  • Professional Discussions of CAA and Approaches to Treatment
  • Ongoing Research Efforts on CAA:
• Related Videos:

Cerebral Amyloid Angiopathy (CAA): Overview

If you have been diagnosed with CAA, it may be because you suffered a bleeding stroke and a brain MRI subsequently showed a pattern of microbleeds characteristic of CAA. At some point, the doctor or neurologist will explain that a certain kind of proteins, called “amyloids,” have built up in the walls of blood vessels in your brain, and weakened the walls, leading to a stroke. You will probably be told that the causes of CAA are not well-understood and there is no known medical treatment that has proven to be successful. You should definitely not let yourself be discouraged, however, since CAA affects millions of people and massive research efforts are underway at top universities and research centers.

Perhaps you wonder, “how can this possibly happen to me?” The surprising fact is that the chances of your having CAA may be as much as 25% at age 75 and as high as 50% at age 90. Until you have a stroke, you would not be aware of your CAA since there are few symptoms other than possible small memory lapses — for which there would be many other possible explanations.

Although heredity is a possible cause of CAA, such cases are fairly rare. The principal risk factor is age, with CAA being uncommon before the age of 60 or 65. Moreover, there is not even a definitive test for CAA other than a brain biopsy, which would rarely be recommended. Instead of a definitive diagnosis, you may be told that your have “possible CAA” or “probable” CAA. This diagnosis would likely be based on the Boston Criteria or Modified Boston criteria, which take account of the size and location of your brain bleed(s) and micro-bleeds as shown on an MRI. Since so little is known about the causes of CAA, the guidance you receive from your doctor may be limited, but it may possibly include:

• Take your blood pressure regularly and — if you possibly can — try to make sure that the systolic pressure stays under 120. (Systolic pressure is the top number on your blood pressure result, diastolic is the bottom number). You may be given medication to take if your blood pressure goes over 120. Don’t worry if your blood pressure sometimes spikes above this level, because it is your average blood pressure that matters. (Note: Lisinopril is one of the blood-pressure lowering drugs that may be prescribed. Blurred vision is one of its possible side-effects, although it may affect only a few percent. Other blood-pressure lowering drugs tend to have side-effects, too.)
• Adopt a so-called Mediterranean diet (a rather general concept) or another type of heart-healthy diet. A Mediterranean diet is traditionally based on fruits, vegetables, whole-grain bread, potatoes, beans, nuts, fish, poultry, olive oil, and dairy products.

You may receive an estimate of your chance of a recurrent stroke, which may be high–as much as 10% a year in one case that we are familiar with. However, there are many things that you can do that may help.

About this site:

Important notice: The team developing this site has hundreds of hours of personal experience in learning about and in dealing with CAA, and we have graduate degrees from MIT, Stanford, and Oxford. We want to share what we have learned and are still learning with others–and we eventually hope to learn even more from you and other visitors to this site. However, we do not have medical degrees or backgrounds, so this site should only be used as a guide or reference tool.

What you can do to get better–the importance of blood pressure, sleep, stress, exercise, a Mediterranean diet

Keep your (systolic) blood pressure under 120. As you can see from the graph below, the risk of a recurrent stroke stays almost as low as possible if the systolic blood pressure is below 120–or even 130.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737594/

Get better sleep. Amyloids are cleared out of the brain during the deep sleep phase (phase three) that comes just before the REM (rapid eye movement) phase. Therefore, getting an adequate amount of deep, restful sleep may be important in reducing the risk of stroke recurrence. Since the length of deep sleep tends to decline significantly with age, getting adequate deep sleep may require a special efforts (avoid caffeine in the late afternoon or evening, avoid stressful activities close to bedtime, sleep in a dark room). You may want to improve your sleeping arrangements (installing curtains that keep your bedroom as dark as possible, or making sure that your blankets don’t keep you too warm). Since amyloids seem to be cleared during hard-to-achieve deep sleep, it might be useful to have your sleep monitored by a professional sleep lab, or you could investigate sleep monitoring devises such as the OURA ring or many others. (Some find that the results are not always accurate.)
https://www.nih.gov/news-events/nih-research-matters/how-sleep-clears-brain

Reduce your stress. There may be evidence that heavy, prolonged stress can raise your blood pressure. This is important to consider since management of your blood pressure may be the single most important thing you can do to reduce the risk of another stroke.

To control your stress, meditation may be very helpful, and–depending or your interests or resources–perhaps you could consider acupressure, biofeedback or listening to music. Taking walks in nature may be one of the best things you can do. If you are interested in learning about meditation, a starting point might be Matthieu Ricard’s “The Art of Meditation.”

Exercise. Although exercise does not directly protect against CAA, aerobic exercise in particular may be effective in lowering blood pressure, which is perhaps the single most important thing you can do to avoid the recurrence of a stroke. Exercise may also be important in order to regain weight and muscle mass that has been lost during a stroke.https://pubmed.ncbi.nlm.nih.gov/11926784/In addition, exercise seems to have anti-inflammatory effects in the brain while also having motor, temperament, and sociability benefits.
https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-019-1534-0.pdf
Finally, some studies show that aerobic exercise can increase the clearance of amyloids from the brain.
https://www.peertechzpublications.com/articles/AADC-4-113.php#:~:text=One%20of%20the%20most%20important,final%20removal%20from%20the%20periphery.

Adopt a Mediterranean diet. A Mediterranean diet is traditionally based on fruits, vegetables, bread, potatoes, beans, nuts, fish, poultry, olive oil, and dairy products. Lamb and other meats can be consumed in moderate amounts. Wine, also in moderate amounts. Sugary beverages and highly processed foods are limited. A DASH diet might be an acceptable alternative since it is designed to help lower blood pressure, which seems to be so very important with CAA. Of course, the best diet might be a vegetarian one–or as close to that as is practicable.

Use extra virgin olive oil with oliocanthal. Some “extra virgin cold press” olive oils contain oliocanthal, which appears to be helpful in reducing amyloids. Few brands of olive oil list the oliocanthal content on their labels, but you can recognize its presence by a slight or strong stinging aftertaste in the back of your throat. Auburn University’s Pharmacy School is currently conducting a study. (And studies on mice seem to demonstrate a strong positive effect.) Without the results of the Auburn study, however, it is difficult to know how much olive to consume in order to reduce CAA risks.
https://www.sciencedirect.com/science/article/abs/pii/S0955286315001898

Use turmeric (curcumin) as a spice. Turmeric is well known for its anti-inflamatory benefits, and appears to have considerable potential for treating caa. In order to have a noticeable benefit, however, turmeric might need to be incorporated into meals almost on a daily basis.
https://www.researchgate.net/publication/281147029_Chronic_administration_of_Curcuma_longa_extract_improves_spatial_memory-related_learning_ability_in_aged_and_Alzheimer’s_disease_Model_rats

Vitamin D and Omega 3. They seem to have some potential to reduce the risk of CAA, or other conditions such as cancer or heart attacks. While the benefits for CAA in particular seem to be unproven, both vitamin D and Omega 3 are important elements of a healthy diet and are worthy of attention.

Other things worth considering: less saturated fat, intermittent fasting

Eat less saturated fat. While there may be no obvious direct link between consumption of saturated fat and CAA, there does seem to be good evidence that it significantly increases the risk of cognitive impairment and dementia which are among the possible outcomes of CAA.
https://pubmed.ncbi.nlm.nih.gov/29701155/

Intermittent fasting. It has become popular as a means of weight loss. It may involve alternate day fasting, periodic fasting, or fasting daily for 14-16 hours (a period that is often arranged to include sleep hours). The potential benefit for CAA is that intermittent fasting might destroy senescent (aging) brain cells, including microglia, since senescent cells may interfere with recovery from a stroke.
According to a Harvard report, intermittent fasting offers has possibvle life extension benefits.
https://news.harvard.edu/gazette/story/2017/11/intermittent-fasting-may-be-center-of-increasing-lifespan/

Notice: If you have lost significant weight as a result of your stroke, it may be difficult to incorporate intermittent fasting into your recovery program until your weight is back to normal.

Sleeping on your side. While the importance of sleep is strongly emphasized above, it may also be worth considering that sleeping on your side may make it easier for waste products (presumably including amyloids) to be removed from your brain.
https://www.sciencedaily.com/releases/2015/08/150804203440.htm

Pay attention to copper. There is evidence that copper (which may accumulate overnight in water in copper pipes) may increase the severity of Alzheimer’s disease. Since copper also has important benefits, it is hard to make any firm recommendation.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3767519/

Some things to avoid: salt, aspirin, fish oil, blood thinners

Salt. Sadly, it may need be limited in order to keep blood pressure as low as possible. A Harvard newsletter (link below), suggests that systolic blood pressure can be lowered by as much a 9 points (9mmHg) when daily salt consumption is limited to 1100mg of sodium. Keep in mind that for most people, the vast majority of salt comes from processed foods which, in any case, you should strive to eliminate from your diet. Also note, however, that too little salt can lead to headaches, balance problems, and possible long term health issues. Finally, keep in mind that people differ considerably in their sensitivity to salt.
https://www.health.harvard.edu/heart-health/take-it-with-a-grain-of-salt

Aspirin, fish oil, and blood thinner medicine. Aspirin and fish oil should be avoided since they are blood thinners that will increase the risk of stroke. Important note on Aspirin. It is often prescribed by doctors when there is a risk of stroke caused by a clot. Aspirin is to be avoided in cases like CAA, where there is a risk of a bleeding stroke.

Alcohol. While moderate alcohol consumption may involve little risk, heavy use may significantly increase the risk of cognitive impairment or dementia.

Calcium supplements. There is some evidence that calcium supplements can increase the risk of dementia in older women who have cardiovascular disease or have already suffered a stroke. Older women who feel they need calcium supplements to reduce the risk of a bone fracture during a fall, may wish to consult a doctor for advice. Here is a link to the research, which is based on a small sample size, but is widely cited nonetheless.
https://pubmed.ncbi.nlm.nih.gov/27534711/

Foie gras. Although the food you eat is unlikely to have any effect on the level of amyloids in your brain, the amyloid content of fois gras can be so exceptionally high that it should be avoided. (Since these results were based on studies of mice that were fed large amounts, they may not matter to humans consuming foie gras a few times per year).

Aducanumab. There is no evidence that the monoclonal antibody Aducanumab, which is a new and very costly treatment for Alzheimer’s Disease is useful in treating CAA.
https://www.massgeneral.org/news/press-release/Doctors-warn-against-off-label-use-of-new-alzheimers-drug-for-cerebral-amyloid-angiopathy

Useful references (some are quite technical):

Many of the citations below refer to experiments that, while promising, are conducted on mice rather than on humans, or research that is only in the clinical trial stage, or for which clinical trials have not yet begun.

General references (non-technical)

“My Stroke of Insight,” by Jill Bolte Taylor. The experience of a neuroscientist, who suffered a stroke and observed her mental processes shutting down, and then fought to recover.
https://www.penguinrandomhouse.com/books/304515/my-stroke-of-insight-by-jill-bolte-taylor/

“Hallucinations,” by Oliver Sachs. This book describes hallucinations similar to those that might occur after a bleeding stroke in the occipital lobe. Located in the posterior portion of the brain, it is responsible for visual processing.
https://www.barnesandnoble.com/w/hallucinations-oliver-sacks/1108022983

“The Angel and the Assassin,” by Donna Jackson Nakazawa. A science writers view of the role of microglia cells in healing, or actually doing harm, following a stroke.
https://www.barnesandnoble.com/w/the-angel-and-the-assassin-donna-jackson-nakazawa/1131300439

Driving with Hemianopsia (Partial Visual Field Loss After Stroke)

Driving with Hemianopsia. After a bleeding stroke, many patients will find that they have lost half of the visual field in each eye, which means that they will only see the left half or the right half of their normal visual field. This condition is called hemianopsia. In some states, patients with hemianopsia are not allowed to drive. In others (including California) the ability to drive with the condition depends on passing a driving test. According to many studies (and the reference below), the ability to return to driving depends much less on the size of the visual field as on such factors as “cognition, visual neglect, visual perception, alertness, and the ability to compensate.” (Visual neglect refers to a condition where the stroke victim may not be able to recognize a stimulus in a certain portion of his visual filed despite there being no apparent damage in that area.)
http://www.hemianopsia.net/driving-with-hemianopsia

Professional Discussions of CAA and Approaches to Treatment

Cerebral Amyloid Angiopathy: Overview. This article gives a very deep, professional discussion of almost every aspect of CAA, early symptoms, the forms in which in appears, and approaches to diagnosis (including MRI interpretations) and treatment. After each section, click “next” to proceed.
https://emedicine.medscape.com/article/1162720-overview

Cerebral Amyloid Angiopathy: A Different Kind of Stroke. This is a case study of an 81 year old man with CAA, with a comprehensive analysis of his diagnosis and treatment.
https://www.nursingcenter.com/ce_articleprint?an=01376517-201808000-00005

Cerebral Amyloid Angiopathy: A Critical Review
https://www.ahajournals.org/doi/pdf/10.1161/01.str.18.2.311

“A practical approach to the management of cerebral amyloid angiopathy” This article summarizes approaches to the treatment of CAA, while also providing useful images of brain scans following a CAA induced bleed, as well as potential treatments for CAA.
https://pubmed.ncbi.nlm.nih.https://journals.sagepub.com/doi/full/10.1177/1747493020974464

Some possible forms of CAA treatment might include “…(antibody-mediated) removal of aggregated or soluble forms of amyloid-β, reducing amyloid-β production, and nonpharmacological strategies to enhance amyloid-β clearance through perivascular drainage pathways.” The article also points out that amyloid clearance may occur during slow wave sleep.

Ongoing Research Efforts on CAA:

Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition. Promising research on mice, conducted at MIT by Dr. Li-Huei Tsai’s laboratory, showed that stimulation of the brain by 40-hz (40 cycles per second) light and sound drove desirable gamma waves, improved memory, and reduced amyloids in the auditory cortex and hippocampus.  It also produced activation responses in the microglia, astrocytes, and blood vessels. https://www.cell.com/cell/pdf/S0092-8674(19)30163-1.pdf

Oleocanthal-Rich Extra-Virgin Olive Oil Restores the Blood-Brain Barrier Function through NLRP3 Inflammasome Inhibition Simultaneously with Autophagy Induction in TgSwDI Mice.
https://pubmed.ncbi.nlm.nih.gov/31244050/

Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. The accumulation of Aβ (amyloid beta) in the brain seems to be slow with high consumption of “whole grains, fresh fruits, vegetables, legumes, fish, and low-fat dairy products (which provide higher intakes of vitamin B ₁₂ , vitamin D, and n-3 polyunsaturated fatty acids) and by low intakes of refined sugars, French fries, high-fat dairy products, butter, and processed meat.” Also important are “natural phenols present in plant-derived foods, such as green tea, red berries, spices, extra virgin olive oil, red wine, and aromatic herbs.”
https://academic.oup.com/nutritionreviews/article/74/10/624/2349955?login=false

“Current Management and Therapeutic Strategies for Cerebral Amyloid Angiopathy” This paper discuss the potential of CAA-associated molecules that have been identified by proteomic analyses (apolipoprotein E, clusterin, SRPX1 (sushi repeat-containing protein X-linked 1), TIMP3 (tissue inhibitor of metalloproteinases 3), and HTRA1 (HtrA serine peptidase 1)).
https://pubmed.ncbi.nlm.nih.gov/33918041/

“Cerebral Amyloid Angiopathy — Adventures in Neuropathology” This paper presents images of brain tissue stained to show the presence of amyloid peptides in the walls of blood vessels. According to the author, the amyloids can stiffen the blood vessel walls, preventing the blood vessels from closing in case of a bleed.
https://www.youtube.com/watch?v=B7UKd-aSuxQ

APOE immunotherapy reduces cerebral amyloid angiopathy and amyloid plaques while improving cerebrovascular function
According to promising research by David Holzman’s group at the Washington University in St. Louis Medical Center, “HAE-4 not only reduced amyloid but also dampened reactive microglial, astrocytic, and proinflammatory-associated genes in the cortex.”
https://medicine.wustl.edu/news/protein-linked-to-alzheimers-strokes-cleared-from-brain-blood-vessels/
https://pubmed.ncbi.nlm.nih.gov/33597265/#affiliation-1

STAT3 inhibitor mitigates cerebral amyloid angiopathy and parenchymal amyloid plaques while improving cognitive functions and brain networks.
https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01293-5

Relationship between uric acid and cerebral amyloid angiopathy. According to this article, “uric acid in the blood protects the blood vessels from CAA damage to the blood vessel wall, and reduces the occurrence of cerebral hemorrhage.”
https://pubmed.ncbi.nlm.nih.gov/34913811/

Research on ALN-APP. Alnylam Pharmaceuticals has applied to begin clinical trials investigating an “RNAi therapeutic targeting amyloid precursor protein for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy.”
https://www.nasdaq.com/articles/alnylam-pharma-files-clinical-trial-authorization-application-for-aln-app-in-the-uk

Research on NOD2. NOD2 is a “receptor expressed by myeloid cells (including monocytes and microglia activation in mouse models of Alzheimer’s disease. It has a strong effect on the clearance of circulating beta amyloid via blood vessels of the brain.” The focus is on “removal of beta amyloid from the perivascular space, by modulating peripheral innate immunity, rather than targeting CNS plaque formation and clearance.”
ttps://www.biospace.com/article/releases/amorchem-invests-in-a-potential-treatment-for-cerebral-amyloid-angiopathy-and-alzheimer-s-disease/?fbclid=IwAR14AVX0HDLV8bt81mub1PDoAIB_Y_Vz43nLD1rXLKsYxBEC_F3gMpaZSCs

Research of EPPS. According to researchers at the Korea Institute of Science and Technology, a chemical knowa as 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (or EPPS) appears to break down amyloid plaques in the brain.
https://sciencebeta.com/epps-clears-alzheimers-protein/

SchragLab @LabSchrag. “Dramatic picture of an artery that reptured due to caa.” (It is best to see this image in 3D: go to SchragLab @LabSchrag and scroll down to 6 Dec 2021.)

Artificial intelligence and CAA. At Massachusetts General Hospital, researchers are using convolutional neural networks (CNNs) to identify tissue markers common in both AI and CAA. They explored six CNN models of the relationship between “histopathological markers” and AD or CNN including:
– “…Percentage of leptomeningeal CAA area, cortical and white matter CAA area, and cortical and white matter Aβ plaque area…
– Cortical density of iron-positive cells (indicative of hemorrhage and siderosis)…
– Cortical density of reactive astrocytes (indicative of neuroinflammation)
– Density of activated microglia in cortex and white matter (indicative of neuroinflammation)”
https://advances.massgeneral.org/neuro/journal.aspx?id=2119

Related Videos:

Cerebral Microbleeds, Cerebral Amyloid Angiopahthy and Their Clincial Relevance by Sheila Smith, MD
https://www.youtube.com/watch?v=oSb_xKGhytY

Research at MIT on using 40-Hz (40 cycles per second) sound and light to drive desirable gamma waves in the brain, improve memory, and reduce amyloids in the auditory cortex and hippocampus.  The findings are based on experiments with mice. The 40-Hz treatment also produced activation responses in the microglia, astrocytes, and blood vessels.
https://picower.mit.edu/faculty/li-huei-tsai

©Center for Strategic Decision Research 2022

This amyloidangiopathy.com site is not intended to offer medical advice and it cannot replace your physician. If you suspect that you have cerebral amyloid angiopathy (CAA) or any related condition, you should consult your doctor as soon as possible.

Much of the information in this site is based on the experience of single person in otherwise excellent heath, age 75, who was diagnosed as having possible or probable CAA after experiencing a single bleeding stroke in the left occipital lobe and after review of a brain MRI by a radiologist and a neurosurgeon. Since CAA and related diseases can manifest themselves in a wide variety ways, your condition may be quite different. So your physician’s advice and guidance will be particularly important and necessary.