We’ve talked about this before, but I was reminded of the risk during my recent MPI training. If you are a 4/4 male with a personal or male family history of stroke, use supplements (like fish oil) that thin the blood very cautiously. If you have a male relative who suffered a stroke, be suspicious that it may have been Cerebral Amyloid Angiopathy (CAA.) There's a link between ApoE4 and CAA primarily in males. This is a very rare sucesptibility, but important to be aware of if you are taking ANY medication or supplement that thins the blood.
Unfortunately, there is no way to predict who will develop CAA. There's actually no test to diagnose CAA with 100% certainty during a patient's lifetime, but there are several ways to know if this disorder is a strong possibility in a patient with a bleeding stroke. Imaging tests like CT scans or MRI scans can show whether the bleeding occurred in the outer part of the brain (the cortex) where CAA is usually most severe. For those "at-risk" because of family history, similar imaging may reveal micro-bleeds in the cortex that might be a tip-off.
To learn more: http://www.angiopathy.org/faq.html
Caution for 4/4 men: CAA
Re: Caution for 4/4 men: CAA
Here’s an interesting new paper that links CAA to both ApoE4 males and females; males being more severely affected. The interaction appears to be dose dependent with homozygotes being more susceptible. Also interesting was the possible association between CAA and abeta. Perhaps all of us need to be aware of the CAA propensity?
Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer's disease.
https://www.ncbi.nlm.nih.gov/pubmed/27179972
Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer's disease.
https://www.ncbi.nlm.nih.gov/pubmed/27179972
Abstract
Cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease (AD). APOE4 is a strong genetic risk factor for both AD and CAA. Sex-dependent differences have been shown in AD as well as in cerebrovascular diseases. Therefore, we examined the effects of APOE4, sex, and pathological components on CAA in AD subjects. A total of 428 autopsied brain samples from pathologically confirmed AD cases were analyzed. CAA severity was histologically scored in inferior parietal, middle frontal, motor, superior temporal and visual cortexes. In addition, subgroups with severe CAA (n = 60) or without CAA (n = 39) were subjected to biochemical analysis of amyloid-β (Aβ) and apolipoprotein E (apoE) by ELISA in the temporal cortex. After adjusting for age, Braak neurofibrillary tangle stage and Thal amyloid phase, we found that overall CAA scores were higher in males than females. Furthermore, carrying one or more APOE4 alleles was associated with higher overall CAA scores. Biochemical analysis revealed that the levels of detergent-soluble and detergent-insoluble Aβ40, and insoluble apoE were significantly elevated in individuals with severe CAA or APOE4. The ratio of Aβ40/Aβ42 in insoluble fractions was also increased in the presence of CAA or APOE4, although it was negatively associated with male sex. Levels of insoluble Aβ40 were positively associated with those of insoluble apoE, which were strongly influenced by CAA status. Pertaining to insoluble Aβ42, the levels of apoE correlated regardless of CAA status. Our results indicate that sex and APOE genotypes differentially influence the presence and severity of CAA in AD, likely by affecting interaction and aggregation of Aβ40 and apoE.
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Re: Caution for 4/4 men: CAA
I'm confused.
Wouldn't thinner blood help to prevent strokes?
Wouldn't thinner blood help to prevent strokes?
Re: Caution for 4/4 men: CAA
This is way beyond my expertise, but apparently if your blood is too thin it can put you at increased risk of hemorrhagic stroke and CAA. Dr. Bredesen has had a few 4/4 males experience this phenomenon. He believes that fish oil may have contributed to their events. He's asked me to share this caution with you all while the science is sorted out. My guess is that it may be MORE important for homozygote men (especially) especially to achieve their Omega-3 Index (RBC EPA+DHA) goal of >10% with real food to avoid this complication. As a homozygote woman, I'm also paying attention...
Re: Caution for 4/4 men: CAA
This recent 2015 paper also associates e2 with CAA:
'APOE and cerebral amyloid angiopathy in community-dwelling older persons.'
This article is cited by a more general 2016 review:
'The role of APOE in cerebrovascular dysfunction.'
'APOE and cerebral amyloid angiopathy in community-dwelling older persons.'
http://www.ncbi.nlm.nih.gov/pubmed/26341746We conclude that both APOE ε2 and ε4 alleles are associated with more severe cerebral amyloid angiopathy, and the direct effect of ε2 is masked by the allele's negative association with comorbid Alzheimer's pathology. APOE ε4, but not ε2, is associated with capillary amyloid angiopathy.
This article is cited by a more general 2016 review:
'The role of APOE in cerebrovascular dysfunction.'
http://www.ncbi.nlm.nih.gov/pubmed/26884068ApoE4-induced detrimental CV changes include reduced cerebral blood flow (CBF), modified neuron-CBF coupling, increased blood-brain barrier leakiness, cerebral amyloid angiopathy, hemorrhages and disrupted transport of nutrients and toxins. The apoE4-induced detrimental changes may be linked to pericyte migration/activation, astrocyte activation, smooth muscle cell damage, basement membrane degradation and alterations in brain endothelial cells.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
Re: Caution for 4/4 men: CAA
It's true, not only for apoe 4/4 men, but for all people on vegan diet. That's why Dr. Fuhrman is especially cautious about salt consumption for vegans; he mentioned increased stroke risk, too.Juliegee wrote:This is way beyond my expertise, but apparently if your blood is too thin it can put you at increased risk of hemorrhagic stroke and CAA. ...
That's probably even more risky for me personally, with my low platelets count (they were low even before the diet, when I ate lots of meat and saturated fat). One more reason to avoid added salt and be careful with Omega 3 fish oils.
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Re: Caution for 4/4 men: CAA
This is all so interesting... I am female, 3/4 and my grandfather died of a heart attack in his low 40s. I know I have at least a couple markers with variants for caa. Should I be worried and watch my fish oil supplementation? Is 1000 DHA daily too much to thin the blood if this condition is a concern? Thank you!
Re: Caution for 4/4 men: CAA
For what it's worth, I saw a reference to the following paper this morning:
Omega-3 Therapy Is Associated With Reduced Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Device
https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.118.005082
Referenced via the following tweets (from latest to earliest, in the twitter way):
Thomas Dayspring @Drlipid
Hopefully this helps put to rest that erroneously accepted belief that bleeding is a side effect of N3FA
Dariush Mozaffarian @Dmozaffarian
Yes, our new in press findings based on a randomized controlled trial of fish oil, suggest that omega-3’s actually reduce bleeding during surgery
Emmanuel @eakintoyeMD
Interesting! In our upcoming secondary analysis of the OPERA trial, we found similar trend towards lower bleeding risk with omega-3 in cardiac surgery patients. Could this be a novel indication for omega-3?
Nir Uriel, MD @NirUrielMD
New work by our group in @CircHF spearheaded by Dr. Teruhiko Imamura re: attenuation of GI bleeding events in pts with LVADs on Omega-3 FA, possibly from reduction in TNF-alpha/ Angiopoetin-2 [and then a reference to the paper cited above]
Of course, this doesn't necessarily have anything to do with hemorrhagic strokes.
Omega-3 Therapy Is Associated With Reduced Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Device
https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.118.005082
Referenced via the following tweets (from latest to earliest, in the twitter way):
Thomas Dayspring @Drlipid
Hopefully this helps put to rest that erroneously accepted belief that bleeding is a side effect of N3FA
Dariush Mozaffarian @Dmozaffarian
Yes, our new in press findings based on a randomized controlled trial of fish oil, suggest that omega-3’s actually reduce bleeding during surgery
Emmanuel @eakintoyeMD
Interesting! In our upcoming secondary analysis of the OPERA trial, we found similar trend towards lower bleeding risk with omega-3 in cardiac surgery patients. Could this be a novel indication for omega-3?
Nir Uriel, MD @NirUrielMD
New work by our group in @CircHF spearheaded by Dr. Teruhiko Imamura re: attenuation of GI bleeding events in pts with LVADs on Omega-3 FA, possibly from reduction in TNF-alpha/ Angiopoetin-2 [and then a reference to the paper cited above]
Of course, this doesn't necessarily have anything to do with hemorrhagic strokes.
Re: Caution for 4/4 men: CAA
Welcome Newtoapoe4!Newtoapoe4 wrote:This is all so interesting... I am female, 3/4 and my grandfather died of a heart attack in his low 40s. I know I have at least a couple markers with variants for caa. Should I be worried and watch my fish oil supplementation? Is 1000 DHA daily too much to thin the blood if this condition is a concern? Thank you!
Yes this is an interesting subject, I think the ApoE risk is more with 4/4 carriers who have a family history, and higher in men than women. That said, you wrote that you have a couple of variants for CAA, so my best advice would be to discuss this with your health care practitioner; if you don't have one here are some great tips for searching for a practitioner . It gets a bit convoluted as Omega 3's are recommended by Dr. Bredesen (1 gm/day DHA) and many others for brain health, but when CAA may be a factor care should be taken. I'm sorry I'm not more help on this topic for you. Here are the posts I found here on ApoE4.info pertaining to CAA if you want to check them out for further information.
As you will find as you explore this site, you are surrounded by like-minded, caring and courageous people who are determined to reverse, prevent and stop dementia, AD and cognitive decline in its tracks! As you will also find there is a huge amount of information in these amazing pages. Here are a few highly recommended pages that will give you great places to start taking a deeper dive into the site: the Wiki Page, where you will find some more in depth topics; "How-To" get the most out of the APoE4.info website page, is very easy to use and will allow you to spend your time on the site more efficiently. I also highly recommend the Primer it's a great place to start and to learn more about AD, it was written by Stavia, one of our most active members who is also a doctor, and is E4/E4 herself.
We would love to hear more of your story and what has brought you to ApoE4.info, feel free to post on the Our Stories forum anytime.
We are excited to have you with us on this journey, please feel free to reach out to me and others as questions and concerns arise, we are in this together and are here to support, uplift, and encourage each other along the way.
Find your joy and hope in each new day and each new discovery along your path,
Deb
Deb
Functional Medicine Certified Health Coach
Enrolled in Reversing Cognitive Decline for Coaches
Choose Hope
Functional Medicine Certified Health Coach
Enrolled in Reversing Cognitive Decline for Coaches
Choose Hope
Re: Caution for 4/4 men: CAA
A recent study found that LOW LDL (<70mg/dL) is correlated with intracerebral bleeds. This caution may be particularly relevant for our 4/4 men already at an increased risk of CAA.