I'm 45 and just got the news

Well, yes, a pretty lousy "club" that you have joined. Like Laura2020, I also started on Leqembi after my AD diagnosis (I just had my 21st infusion). My Dad had some form of dementia, and my Mom probably had AD, so my diagnosis shouldn't have been a surprise. But still, I was hoping it the problem was something else. After a few days of despondency about the news, like you, I devoted my energies to researching information about treatment options. I'm hopeful that in my situation, I've started the Leqembi treatment early enough such that I might have results similar to those in the no/low tau group in the Phase 3 Leqembi clinical trial. Within this subgroup, 76% of those on Leqembi at least maintained the same cognition level over the 18 month trial. The message seems to be that regarding Leqembi effectivity, the earlier the treatment starts in the disease process, the better the outcome. The same general trend also seems true for Kisunla, the other FDA-approved anti-amyloid drug now available.

The often-quoted 27% reduction in cognitive decline for Leqembi came from the Phase 3 trial. There were 875 on placebo, 853 on Leqembi, all for 18 months. At the start of the trial, everybody took a specific cognitive test: the Clinical Dementia Rating, and they summed the scores from the various portions of the test to form something called the CDR-SB score. The Clinical Dementia Rating is based on memory, orientation, judgment, community affairs, home hobbies, and personal care. A score of zero in a category means no impairment, a score of 3 means severe impairment. As an example, for home & hobbies, a score of 0 indicates life at home and hobbies are well maintained. A score of 0.5 in this category indicates these abilities are slightly impaired. For a score of 1 there is mild but definite impairment, very restricted interests for a score of 2, and the 3 score means no signification function in the home / hobbies. This test is administered in research settings and requires a trained clinician to administer, interpret, and score the test after interviews with both the patient and a care partner.

At the end of the 18 month trial, everybody repeated the test. They then compared the reduction in CDR-SB scores for those on placebo versus those on Leqembi, and that is the source of the famous 27% statistic. This is partly what drove the FDA to approve Leqembi as a treatment for AD, as the clinical trial demonstrated a slowing of the progression of the disease as measured by the CDR-SB.

Another way to look at the statistic is to inspect the plots of CDR-SB scores versus time for the clinical trial (available on the Leqembi website), for both those on placebo and those on Leqembi. If you draw a horizontal line, you can easily see how much "extra" you get at the same cognitive level, comparing when taking Leqembi versus those on placebo.

I'm not such a big fan of the 27% statistic, because, as the saying goes, "your mileage may vary." Eisai has published in the Phase 3 trial report on Leqembi the percent slowing for various subgroups. For example, for women the average slowing was 12%, and 43% for men. For those under 65, the average slowing was 6%, for those over 75 the average slowing was 40%. For APOE4 noncarriers, the average slowing was 41%, compared to 30% for heterzygotes and a -22% for homozygotes (i.e. for homozygotes, those on Leqembi had worse cognitive decline compared with those on placebo). Of course, if you happen to be an older female who is a heterozygote, you would like a prediction on how Leqembi might help your specific situation. Unfortunately, there apparently isn't enough data to generate such statistics. Hence, we are left with the overall 27% value, plus some knowledge about variations by gender / age / APOE4 status.