Hi Julie,Julie G wrote: ↑Tue Oct 25, 2022 5:37 am ...Perhaps because of the media storm proclaiming "historical" results with Lecanemab, I don't see a discussion about its efficacy.
1) Lecanemab does not improve cognition and does not stabilize Alzheimer’s. It simply slows decline in the early stages.
2) The slowing of decline was in between that of aducanumab (22% slowing in its best trial, none in another trial) and donanemab (32% slowing).
3) As mentioned by other posters, the side effects include brain microhemorrhage and brain edema. Thus some people may actually get worse instead of slowing their decline.
Detailed results on lecanemab's CLARITY trial in about 1800 participants with confirmed clinical diagnoses of MCI/Mild AD with elevated amyloid on PET scans will be presented at the CTAD conference on 11/29 and may address the issues you raise
The comment below by Dave Morgan from Michigan State in the Comments section of the 9/28 issue of AlzForum https://www.alzforum.org/news/research- ... ne-results puts the clinical slowing in perspective as expected from a single focus on amyloid and may support the need to address elevated levels in some ApoE 4 individuals, in addition to insulin resistance, mold, inflammation, etc. :
.The 25-40 percent reduced rate of decline is similar to the contribution of amyloid to cognitive decline variation in the pathology studies from the ROSMAP cohorts.
NOTE: Additional of information on the source of the data mentioned in AlzForum:
The ROSMAP study is a combined cohort from the Religious Orders Study (ROS) started in 1994 and the Rush [Chicago] Memory and Aging Project (MAP), started in 1997. They have often been combined as one cohort to identify resilience and risk factors for cognitive decline, dementia, and other health outcomes. Religious Orders Study and Rush Memory and Aging Project.
Below is an excerpt from a 2018 analysis of the autopsied neuropathology findings from the ROSMAP study. ApoE 4 status is not addressed in this analysis; possibly because recruitment occurred in the 1990's The AD/Alzheimer's pathology referred to below included "neuritic plaques, diffuse plaques and neurofibrillary tangles" based on autopsies. Bolded sections are added by me Person-specific contribution of neuropathologies to cognitive loss in old age
This does seem to show that while focus on AD pathology may account for 50% of cognitive impairment on average, other factors may well help individuals to either be resilient or to show continued cognitive decline.Characteristics of study participants
Participants [N=1079] were followed annually for up to 22 years (mean=8.3, Standard deviation (SD)=4.8) and died at a mean age of 89.7 years (SD=6.5). All had undergone brain autopsies...Considerable decline in cognition was observed over the course of follow up; this was evident from the difference between the starting level of cognition (mean=−0.10, SD=0.62) and the level proximate to death (mean=−0.84, SD=1.11). By the time of death, 459 participants (43.2%) were diagnosed with the clinical syndrome of AD dementia, 18 (1.7%) with another primary cause of dementia, 261 (24.6%) with mild cognitive impairment, and 324 (30.5%) had no cognitive impairment ...
Neuropathology was ubiquitous, with 94% of participants having 1+, 78% having 2+, 58% having 3+, and 35% having 4+. AD was most frequent (65%) but rarely occurred in isolation (9%). Although AD accounted for an average of about 50% of the observed cognitive loss [across the cohort], the proportion accounted for at the individual level ranged widely from 22% to 100%...the fact that considerable variability remains unexplained suggests that the true impact of any specific neuropathology is actually much less than what was observed here.... An increased focus on resilience may facilitate the identification of novel therapeutic targets that can be applied much more broadly and may have an even greater impact on cognitive outcomes than interventions targeting specific disease mechanisms.
I have seen no data to date that shows that trial participants who received lecanemab showed a greater rate of cognitive decline as a result of ARIA-E or ARIA-H greater than those taking lecanemab who did not experience ARIA. This of course will be important to see in detail at CTAD and will presumably be of great importance to the FDA in looking at risk/benefit analyses. To date, no reports of deaths due to lecanemab have been reported.
Below is an excerpt of the data posted by Biogen on 9/27. [emphasis added]:
LECANEMABThe incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. The incidence of symptomatic ARIA-E was 2.8% in the lecanemab group and 0.0% in the placebo group. The ARIA-H (ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) rate was 17.0% in the lecanemab group and 8.7% in the placebo group. The incidence of symptomatic ARIA-H was 0.7% in the lecanemab group and 0.2% in the placebo group.
From what Chicagogirl has posted and materials presented at AAIC and CTAD presentations, the AHEAD prevention trial informed consent, approved by each study site Institutional Review Board (IRB) presents risks in detail. Titration to full dosing takes 8 weeks and dosing is paused and an additional MRI done if someone experiences suspected symptoms of ARIA-E or ARIA-H. The trial doesn't require that someones stop taking supplements that would be consistent with the Bredesen protocol or change their diet, exercise and social and intellectual engagement.
To paraphrase a comment from one neurologist, not speaking specifically of any treatment, said at AAIC that stuck with me: "Patients with mild dementia and their families don't ask what the CDR score will be, or what the P-value is: they ask how long they will be able to play with their grandchildren or keep driving or do other things of meaning in their lives. An extra 6-12 months is very meaningful to them."