Newbie ES

Tom Huff

Background and introduction.

I am a retired environmental chemistry professor who has experienced memory changes for the past couple years. This included headaches, dizziness and an inability to focus. It took 5 months to get an appointment with a neurologist. I finally got in in March 2025. (The waiting room was empty!) She ordered a w-w/o MRI, pTau & AB ratio test, and Neuropsyche evaluation..

The MRI took 12 weeks to schedule as the neurologist and the hospital radiologist battled over who was responsible for obtaining insurance authorization. It took 6 more weeks to get the MRI results which were only the radiologist’s report on my patient portal. There was a 1 year wait for the neuropsyche. Still haven had one. At that point the neurologist had walked away from her practice with no reason given.

The MRI showed cerebral atrophy in part from small vascular ischemia as well as other changes beyond what is expected for a 71 yo.

The NP saw my bloodwork & ordered a PET scan. Another 5 weeks. At that point, I found a new neurologist who is excellent. I have the neuropsyche scheduled for late March ‘26.

The APOE showed E3/E4. The pTau217 to AB42 ratio was 0.0133.

Meanwhile, my symptoms are getting worse, and I still haven’t had a diagnosis. So I’m looking forward to hearing from folks and any advice from those with the D word!

LBC83

As I like to say, welcome to the club you probably hoped you would never join :)

I'm also E3/E4, I scored 25/30 on a MoCA in Jan 2024. My MRI showed "Minimal white matter disease which is nonspecific but likely reflective of chronicmicrovascular ischemia." My lumbar puncture results confirmed the presence of amyloid plaque, and my detailed cognitive exam resulted in an MCI diagnosis (mild cognitive impairment). I started on Leqembi in August 2024. That was the only choice at the time, now people have the option of Kisunla or Leqembi for infusions. I recently had my 39th infusion. I'm fortunate as I have zero reactions to the infusions or to Leqembi, I walk out of the infusion center feeling the same as when I walked into the infusion center. I'm hoping to switch to a subcutaneous version of Leqembi for maintenance dosing in early 2026 (the device is referred to as IQLIK, it is a self-administered shot once-a-week). I had a second MoCA about 9 months after starting on Leqembi and I scored the same. I take that as a success - stable cognition isn't something often discussed within the context of Alzheimer's Disease.

I don't use the "D word", as technically, MCI is distinct from dementia. One popular cognitve test used in clinical trials is the Clinical Dementia Rating - Sum of Boxes (referred to as CDR-SB). A score of zero is for a person with normal cognition. People with MCI have low scores, next comes people with mild dementia, the moderate dementia, followed by the highest scores for people with severe dementia.

Tom Huff

https://alzconnected.org/discussion/comment/260595#Comment_260595

Thank you for your welcome note, as well as your candor. I am finding so much information here and many personal stories. One of my impairments is a hard time focusing, like reading the same page in a book over and over again and still not remembering what it said, so it will take a fair amount of time to get through a lot of it.

My neurologist and I discussed leqmbi and kisunla but decided against it for now. We’re waiting for more data as the usage increases, and I have other health factors that could increase the severity of adverse reactions. This may change after the detailed cognitive exam. The MoCA was easy for me, but after being a professor for 30 years, I need to detailed cognitive exam as a baseline and to see if my skill set is masking symptoms I have had for several years. But reading the stages, I suspect I’m in the MCI group. Time will tell!

Best wishes to you and hope to see you around!

LBC83

https://alzconnected.org/discussion/comment/260620#Comment_260620

I am usually not one to question the judgement of a Neurologist, but I wonder if your Neurologist is up-to-date on Leqembi / Kisunla? I attended the Alzheimer's Association International Conference (AAIC) in Toronto this past summer. Both Eisai (developer of Leqembi) and Eli Lilly (developer for Kisunla) presented updates on their respective drugs. Eisai presented preliminary results for a multicenter, real-world study with 15 health care providers across the U.S. where they plan to treat 320 patients. They presented preliminary results from 9 health care providers treating 178 patients, for an average treatment period of 375 days (i.e. a bit over one year). 87% had continued treatment, with 13% dropping out. Most of the dropouts were due to "other" reasons (i.e. not cost, or time commitment, or ARIA). In terms of cognitive changes, they reported that 84% of the patients remained stable or improved.

Eisai also reported on 4-year data from people who were enrolled in the Phase 3 trial and either continued on in the open-label extension period or they switched from placebo to receiving Leqembi at the start of the open-label extension. They found that among those who started on Leqembi with low tau tangle levels, 69% of this group experienced no cognitive decline over the 4 year period. The tau tangle level may perhaps be thought of as an indicator of the AD disease stage. In other words, the earlier people start on Leqembi (or Kisunla), the better the performance.

Eli Lilly presented their analyses of data with Kisunla after 76 weeks of treatment, they found a 31% risk of people on Kisunla progressing to the next clinical stage after 76 weeks of treatment.

A problem with the "waiting for more data" paradigm is that these drugs do not make up for lost time. Once neurons are damaged due to the progression of AD, they cannot be repaired or replaced. Both Kisunla & Leqembi are anti-amyloid drugs, meaning that they removing amyloid plaques from the brain. This is a good thing to do, but amyloid plaques are not the primary cause of cognitive decline associated with AD. Rather, tau tangles, which are found within neurons, are the key driving factor in destroying neurons. Researchers theorize that high levels of amyloid plaque trigger the formation of tau tangles. Hence the desire to quickly remove as much amyloid plaque as can be done safely and effectively.

Another way to say this is that the longer a person waits to start on Leqembi / Kisunla, then the less effective the drug will be. That is due to the nature of AD and how these drugs work in removing amyloid plaque.

As with other areas of life, there is a risk-reward calculation with Leqembi / Kisunla. The rewards are clear - removal of amyloid plaque and slowing of cognitive decline. The risks are also clear from the Phase 3 trials for these drugs: brain swelling / bleeding (referred to as ARIA), and infusion-related reactions. These reactions need to be taken seriously, but again, the cognitive decline associated with AD is also a serious problem. I like to compare the risk of Leqembi / Kisunla to driving a car on the highway. Clearly, driving at high (legal) speeds gets you to your destination faster, but if you happen to get into an accident, the odds of significant damage to your body are much higher than if you drove on side streets at 25 mph to get to your destination. We often don't think about this risk/reward calculation when driving, but it is there nonetheless. With Kisunla/Leqembi, patients are trading off more quality time at a higher cognitive level versus the risk of ARIA and/or infusion-related reactions. This is a personal decision, as there is no "one size fits all" solution to this risk / reward balance for anti-amyloid medications.

GEH

Hi Tom,

You have joined the club no one wants to belong to but we welcome you none the less. I have found this group a great source of information, support and a safe place to blow off steam. If I may be so bold, I would highly recommend you NOT hold off on the decision to take the infusions of either Leqembi or Kisunla. Theses are drugs us Alzys have never had available to us before. I am not familiar with the Kisunla but I did some research on Leqembi before I started treatments 8 weeks ago. It is my understanding that Leqembi has the ability to help remove plaque from the brain and also help prevent buildup of more plaque by removing the protofibriles(?) that are the precursors to placque. Amazing!! The sooner treatment is started the less damage is done to healthy brain cells. I am a person that has been allergic to everything my whole life and I was quite apprehensive with my first infusion. But I have had absolutely no adverse reactions. The worst thing I could say about the infusions is that they are boring..lol .. so I bring things with me to help pass the time. I just had my first MRI since starting infusions and MRI was good showing no signs of any bad reactions etc. 😊

Dorse

Thanks for sharing.

Tom Huff

https://alzconnected.org/discussion/comment/260624#Comment_260624

Thanks again for your reply and insight. It is appreciated. As to my neurologist, she is a top neurologist at UVA hospital system in high-tech Northern Virginia. She is highly capable of reading current peer-reviewed research papers performed on these drugs independent of the claims by pharmaceutical companies. She is very current on the research and aware of the actual approval process with the FDA. I am also a published research scientist for 33 years with studies on a wide variety of topics ranging from biomedical, bioengineering, biopharmaceutical and environmental.

This is not to brag, but to dispel the notion that this is advice from an uniformed "antivaxer type" with little knowledge of the subject. We discussed all this valuable information in your reply and determined that a near 25% risk of side effects for a person (me) with a long history of serious cardiovascular illness is too high of a risk for me. It would also require a 1 hour drive each way the Charlottesville for the infusions which is risky for someone who gets confused easily when driving distances.

Again, I appreciate your insight and don't wish to be argumantative in any way, I simply wanted to asssure folks that care and consideration was taken in my decision to forgo these drugs until I actually have a diagnosis that rules out vascular dementia (which matches some of my MRI results) or any other form of demantion.

Best to you and your family during the holidays.

Tom Huff

Thank you for your insight. It is much appreciated, and I ake it to heart,

Please see my comment to LBC83. At this point, I don't have a definitive diagnosis as indications are it could also be dementia caused by other illnesses. I am have high-risk cardiovascular disease, so adverse side-effects could be worse for me.

And great respect for fellow dementia sufferes, I need to consider the advice of a highly respected neurologist who has examined me rather that pharmaceutical companies' sponsored research.

Again, thanks! Best wishes to you and yours for the holidays!

GEH

https://alzconnected.org/discussion/comment/260744#Comment_260744

Happiest of Holidays to you and yours Tom...All the Best in the Coming New Year! 💖 GE

Michele P

https://alzconnected.org/discussion/74816/newbie-es

If you are near a Mayo Clinic, get a referral from your doctor for The HABIT Program. My husband has MCI, and this program gave him back executive function and focus. They will train you on the Brain HQ online games program. These games build new connections in your brain. At the least, go online and sign up for Brain HQ. Look at Dr. Dean Ornish’s Lifestyle Program. He has clinical trials that showed slowed progression in early stage Alzheimer’s, and in cases, restored loss cognitive function. Your diet, exercise, and stress reduction is critical. Look at foods that break the brain barrier. These foods help cognitive function as well. Keep mTOR enzyme protein levels low in your body. This enzyme, when low, repairs cells and creates new connections in the brain. Look at foods that keep this low. My husband’s scans are showing that this advice is working!