jenwin wrote: ↑Wed Jun 07, 2023 7:41 pm
Thank you so much. I dove deep last night. Can you tell me if APOE4/4 is the same as just APOE4? I see both everywhere. I will definitely read those links (bedtime reading!), but have you seen anything on Lecanemab for people with one variant vs 2? The dr said with 2 copies she is not a good candidate, but with one she should be fine.
Hi again,
This is confusing, isn't it! I'll answer your question about ApoE 4/4 vs ApoE4 first and then give you some real data from the CLARITY trial with about 1800 people taking either Lecanemab or a placebo.
ApoE 4 or ApoE4 (it can be written both ways) and refers to people who carry one or two copies of the ApoE 4 gene, sometimes called the ApoE4 allele
- When articles say "people with ApoE4 have an increased risk of late-life Alzheimer's" or "people with ApoE4 should avoid high levels of saturated fats", they are referring to about 25 % of the population in the U.S. and Europe, with slightly different percentages in other areas of the world, whether or not they have one or two copies of ApoE4.
About 90% of that whole group are like you and your mom, with one copy of ApoE 4 and one copy of ApoE 3 and would be called ApoE3/4.
- That's still about 22% of everyone in the U.S. and Europe and includes you and my three adult children. You and my kids have more of a risk than someone who has two copies of ApoE 3 (called ApoE3/3)--and decades to greatly reduce that risk with a healthy lifestyle.
Only about 2% (2 in every 100 people) in the U.S. carry two copies of ApoE4 and they are referred to as ApoE 4/4. - I am one of them and I am still healthy, with no cognitive or heart disease at age 71. So even with two copies, it is not my destiny or yours to get this disease. I might get Alzheimer's, or heart disease or colon cancer, since they all have occurred in my family, but I have avoided all of them for 71 years even with "high" risk. That tells me that how we live our lives is more important than our DNA.
Below is data from the CLARITY trial of lecanemab. Your mom's doctor is referring to this data when he says she would have less risk with ApoE 3/4. On the chart, ApoE3/4 is "heterozygotes". I circled some key figures in blue and orange for ApoE 3/4, and in red for ApoE 4/4 )"homozygotes".
ARIA-E stands for edema, or fluid seen on MRI scans; ARIA-H stands for micro-hemorrhages (1-5mm), macrohemorhrages (>1cm) or intracranial hemorrhages (what we think of as a stroke) seen on MRIs. Most of these are asymptomatic in both ApOE 3/4 and ApoE 4/4, which is why an MRI is done BEFORE starting on lecanemab and then a few times during the first 6 months or at any time when symptoms are either severe or mild but persistent for several days.
It's hard to see the numbers, but the risk of any kind of temporary brain swelling (ARIA-E) was about 2% for people on placebo, about 11% for people with ApoE3/4 and about 33% for people with ApoE 4/4. Less than 1 in 200 people (0.4%) with ApoE 3/4 had serious ARIA-E (which is treated with IV steroids), while four times as many people, but still only 2% of people with ApoE4/4 had serious ARIA-E. or brain fluid swelling.
Any time there is either a concern about serious effects before an MRI, or evidence of a mild ARIA-E or mild ARIA-H with symptoms, IV infusions are "paused" until the symptoms and signs resolve.
The risk of a serious brain bleed was about 1 in 170 (0.6%) of people with ApoE 3/4 on lecanemab and one in every 500 people who DIDN'T take the drug (on placebo). The risk for people with ApoE 4/4 was about 2% for a serious brain bleed.
That's why your mother's doctor says the risk would be significantly less for her with one copy of Apoe4. It's not no risk and she and you (or her Study Partner) need to discuss how they would monitor her, and how you would report any symptoms. My study site spent LOTS of time with me discussing just that; they welcome questions from family members.
ARIA rates reported for the Phase 3 (CLARITY AD).png
You know so much more already about how to stay healthy. Focus on what you love today, tomorrow and next year, and on enjoying the special times with your mom. She sounds like someone who raised a great adult. You get to write your own future with simple steps you take today.
Nancy
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