Watching Alzheimer’s Take My Grandmother Changed Me! Now I Want to Build Something That Helps

rana

After losing my grandmother to Alzheimer’s, I’ve been thinking a lot about how difficult this journey is for families and caregivers.

I’m an engineer and want to use technology to make people’s lives more comfortable and better in this space, but I know I need to understand the real problems first.

If you’ve worked in dementia care or experienced it firsthand, I’d really appreciate any advice, mentorship, or even a quick conversation

LBC83

I am also an Engineer (BSME from Purdue University). I'm now retired, I was diagnosed with AD in April 2024 and soon started on Leqembi.

The advent of the two anti-amyloid medications (Leqembi & Kisunla) can be a game-changer for those like me fighting this disease. At this point in time, I'd suggest that your engineering skills might be better used on platforms like this website, helping newly diagnosed patients understand the risk/benefit equation for the new drugs. For starters, you could read the Phase 3 trial reports for Leqembi & Kisunla, then the Appropriate Use Recommendations for both drugs (these are all available for free online).

If you then do some simple internet searches, you will see lots of junk science on the web comparing these two drugs. For example, something as simple as the slowing of cognitive decline measured in the respective Phase 3 trials. The two drug companies responsible for Leqembi/Kisunla often compare the slowing in cognitive decline based on different cognitive tests. I'd guess you immediately get the issue, it is like comparing distances in km to those in miles. But more importantly, as noted in the Kisunla Appropriate Use Recommendations, the respective Phase 3 trials for these two drugs were composed of two different groups of people in terms of progression along the dementia degradation timeline. So to restate the problem, there are two drugs on the market to slow cognitive decline. The companies responsible like to report their results in terms of cognitive slowing comparing those on the active drug versus those on placebo. However, the companies frequently publish results using these different cognitive exams. Further, the two groups also are composed of people at different stages in the progression of the disease.

If you think about this problem from an Engineering standpoint, then you might find that the analyses of a group on anti-amyloid medication versus a group on placebo is necessary from the perspective of the FDA to show effectivity of the drug. However, this isn't so useful for patients like me. Rather, we want to know the impact on an individual, not on a group. Eli Lilly (developer of Kisunla) came up with the concept of meaningful within patient change in cognition. They define this as the threshold at which the well-being of a patient and/or their care partner is notably impacted. This seems to me something much more relevant to patients. They have developed plots reporting the risk of meaningful within patient change over 76 weeks for those not taking Kisunla versus those taking Kisunla. Eisai (lead for Leqembi) has taken a similar approach, they have generated curves predicting the delay in progression from MCI (mild cognitive impairment) to mild dementia. For example, they predict a patient who started Leqembi early in the progression of the disease might delay the progression from MCI to mild dementia by 6 years.

Finally, the University of Pennsylvania developed a model to predict changes in cognitition for those on an anti-amyloid medication as a function of the time from tau-onset. If you aren't versed in the AD lingo, simply put, there are two key proteins involved in AD: amyloid (formed outside neurons) and tau (formed inside neuros). By definition, the anti-amyloid medications currently approved by the FDA (Leqembi & Kisunla) only remove amyloid plaque. They seem to slow (but not stop) the increase in tau. The last piece of the puzzle is that tau seems to have a much higher impact on cognition than amyloid. Hence the basic fact that Leqembi/Kisunla only slow cognitive decline - this is because they are only treating a secondary problem related to cognitive decline (amyloid), and not removing tau. Returning to the University of Pennslyvania analysis, their model predicts slow decreases in cognition over 18 months of treatment with anti-amyloid medications for those starting near the time of tau onset. The longer the delay in starting treatment, the higher the slope of the cognitive decline line. This reinforces the concept of starting on these anti-amyloid medications early, rather than later in the disease progression. As if this isn't complicated enough, the University of Pennslyvania also includes three other variables. Namely, they categorize individuals as either resilient, canonical, or vulnerable. Resilient individuals have slower cognitive decline compared with the other two categories, and vulnerable individuals have the highest rate of cognitive decline. My understanding of the concept of resilience may be similar to cognitive reserve. Examples might be people who read lots of books, have an active social life, exercize regularly, etc, might develop high cognitive reserve and be resilient. Those with comorbidities (meaning they have other medical issues besides Alzheimer's) could be vulnerable. Canonical are the rest of the folks who are just you average Jane/Joe.

I'm always amazed that there aren't smart people (such as you) who might devote some time to studying this problem of developing simple explanations of Leqembi/Kisunla including the pros/cons, and publishing their assessment in a group such as this. I get you want to help people make their lives "more comfortable". But with the advent of these new drugs to treat AD, it really is a new world out there for people like me with AD. People newly diagnosed with AD need help understanding these new drugs in simple terms. With a degree in Engineering, you are well placed to perform such a function for the world!

jaycey

I'm a researcher in AI and I was diagnosed with a variety of Alzheimer's 18 months ago. I am prbably an example of "cognitive reserves - I have read in bed every evening since I was 5 years old, I manage a large research group, I do cardio to get blood circulating through my brain, I try to socialize (the toughest for me). However, despite all this, I find managing appointments (getting them into the calendar, and remembering the current day and time as well as the time to leave for the appointments. I find it complicated to manage the travel to get to my appointments (I travel long distances to get to my MRI and infusion. I use Google calendar, a note app, post-its, and everything else I can think of to help with this, but it's not enough. An app that allows entering appointments by voice, checking that they have all the details necessary (address, time, what needs to br brought), and transfering them to a calendar app, finding conflicts and pointing them out. Something like that would be great. Perhaps it could point out that there are no appointments with friends, no sport. Something like that?