Newly diagnosed with MCI

My DW was finally diagnosed with EOAD about 2.5 years ago. It was quite the journey to get there though. 4 years ago my DW, whose business was medical billing. She had 10 doctors who contracted with her business. She started complaining to me that she was having a hard time doing her job, which she had done for the past 20 years, figuring out how to do it. We started with our PCP and was told it was just brain fog from menopause. I didn’t buy that and had her order an MRI. It came back unremarkable showing some brain matter shifting ( which was normal for her age 52). We then went to a Neurol psych and had the grueling 5 hour neuro psych test ( which was as out of network for our insurance) The test came back showing signs that she had primary progressive aphasia and guessing that was it. We we further and contacted Mayo Clinic ( all treatment was out of pocket since once again not in our network). After a week of intensive testing, she was finally given the diagnosis of early onset Alzheimer’s disease. We finally had a diagnosis and were now able to get SSDI and after 2 years Medicare. It really depends on how far you want to take to get a diagnosis. By the time we finally got the diagnosis, she was already past the early stages where medication might have helped to slow the progression. She is now in stages 5/6 and we are living each day to the fullest.

To elaborate on my prior reply, today's "official" confirmation tests for amyloid are either an amyloid PET scan or via cerebrospinal fluid (i.e. lumbar puncture). Blood-based biomarkers are currently used for prescreening for those with AD, not for a definitive diagnosis. Eisai, one of the two drug companies that jointly manufacture and distribute Leqembi (the other is Biogen), has published information on their website regarding wider usage of blood-based biomarker (BBM) as "next generation confirmatory diagnostic technology." They see us in a transition from the amyloid PET scan or lumbar puncture as the current two methods for confirmation of AD to three choices, with the addition of blood based biomarkers. There are several steps in this transition, including the Alzheimer's Association (the sponsor of this forum) publishing clinical practice guidelines for blood-based biomarkers (the guidelines are apparently currently under development), and the companies developing the blood-based tools to receive FDA approval and approval from the Centers for Medicare & Medicaid Services.

The standard pathway nowadays for AD diagnosis / treatment often starts with a visit to a family Doctor, where an quick & easy cognitive test is performed (i.e. MoCA). In my case, my nurse practitioner conducted a test even simpler than MoCA, which I easily passed. But I pushed the point, so my NP referred me to the Cleveland Clinic Lou Ruvo Center for Brain Health. There a more detailed memory test was performed, and I scored low in short-term memory. This lead to a baseline MRI, APOE4 genetic testing, a more detailed neuropsychological exam, blood work and other tests to rule out other possible causes. All of this showed probable MCI, the final test for AD was the confirmatory lumbar puncture.

I might have expected your Doctor to treat your blood-based biomarker prescreening test results as a possible indicator for AD, triggering the above standard process for a definitive diagnosis.

It is easy to see how in the future, when blood-based biomarker testing becomes fully FDA approved and also approved by Medicare, and if this testing becomes a standard part of regular blood work performed by primary care doctors (i.e. similar to the routine checking of cholesterol levels in blood work performed for an annual physical), then this has the potential for opening up a huge demand for drugs like Kisunla & Leqembi.

The other piece of this is the key role Neurologists play in the current pathway for AD diagnosis & treatment. I saw in a Youtube video a Neurologist in a conference sponsored by the Alzheimer's Association answer a question about the role of Neurologists versus primary care doctors in future diagnosis and treatment of patients with MCI or mild AD. The Neurologists noted there were not enough Neurologists in the U.S. to diagnose and treat all of the people with MCI / mild AD. Further, the Neurologist noted that in "simpler" cases (i.e. those without complications like having both AD and other significant brain issues), it is perfectly fine for primary care doctors to diagnose and treat AD with Kisunla & Leqembi. The primary care doctors would need to be linked up with a network to coordinate the detailed cognitive testing, MRIs, genetic testing, etc. But they don't necessarily need a Neurologist to orchestrate the show, again referring specifically to the "simpler" cases of MCI / mild AD.

darylm44 mci is a biggining of the road don't worry as things progress. hopefully by then you will receive help with the progression of the alzheimers or what ever form you may be diagnosed with as there are 50 or so kinds of dementia by some one who has the needed education in this field. i have been under the care of a memory clinic, a fine group of specialists in my case for alzheimers. i am on doneprozol which is keeping me stable as stable can be for a degenerative desease. embrace your situation ,.learn lots.i know you are in a difficult situation , but change is your new word. and some times change you have no control over thank your own brain for that. all in good time you will understand…..you will do ok…

SSorry for last meantvv to say going to goodcBfridayb services

As a final comment for the day, below is one of my favorite plots from a paper titled "Accelerating Alzheimer's therapeutic development: the past and future of clinical trials" by Dr. Adam Boxer & Dr. Reisa Sperling. Box "A" shows the biomarker change for a typical person with AD. Soluble amyloid is detectable at levels above normal about 20 years prior to symptom onset (dashed red line). Two biomarkers trip next at about 15 years prior to symptom onset: amyloid plaque (solid red line), and soluble tau (such as ptau217, dashed blue line). Then comes the dreaded tau tangles (solid blue line), detectable at about 6 years prior to symptom onset. The theory seems to be that is the tau tangles that lead to the cognitive decline associated with AD. Finally, the black line is showing cognitive decline.

Box B is showing Boxer's theory on the impact of treatment with Leqembi / Kisunla when the drugs are introduce after cognitive decline is noticed. Boxer theorizes the soluble amyloid, amyloid plaque, and soluble tau are reduced greatly, but the cognitive decline isn't reduced very much.

Box C shows if a treatment with Leqembi or Kisunla is combined with an anti-tau drug (such as E2814). Eisai is sponsoring an ongoing trial to test E2814 with Leqembi, to see if Boxer's prediction is correct. Note that the black cognitive decline curve is significantly modified with this approach (again per theory, the trial will show whether or not this is truly the case).

Box D is labeled "Prevention" and refers to the AHEAD 3-45 trial. This trial is with Leqembi, where the drug is provided very early in the AD disease progression. The theory (again to be tested with the trial) is that this early application of Leqembi may reduce the amyloid to the extent that there is never a huge increase in soluble tau or tau tangles, and thus no big increase in cognitive decline. Some might call this a solution to AD.

What does all of this have to do with Darylm44's case? Let us return to plot B. Per the information provided by Darylm44 about their blood biomarker readings and, most importantly, how the readings relate to the minimum threshold for AD, it seems Darylm44 might be closer to the -6 year point on Box B (i.e. 6 years before a significant cognitive decline is detectable). I should note that I'm just guessing as, they didn't provide their MoCA score (which is fine, data privacy and all), and I'm not a medical professional.

One more important point - in the Phase 3 trial for Leqembi, they formed a small special group referred to as the low-tau group. This group (which had both people on Leqembi as well as people on placebo) had regular testing performed during the trial to determine their tau levels. This allowed Eisai to determine that for those in this group with low tau who were taking Leqembi, 79% had no cognitive decline at 18 months and 59% had no cognitive decline at 36 months. The subgroup population was small, so it is dangerous to extrapolate these results to larger populations. But still, this seems to imply that starting on Leqembi early, when tau levels are low, might be a key to Leqembi working at its best in scrubbing out the amyloid in the brain, perhaps to the extent that the cognitive decline typically associated with AD is much delayed or maybe even mitigated. As the tau levels provided by Darylm44 in their blood work seem to be very low, it appears Darylm44 might be considered to be similar to a low tau person in the Phase 3 trial for Leqembi, and thus Leqembi might be very beneficial for Darylm44. Lots of speculation in the last sentence, but it seems a Dr familiar with the details of the Leqembi Phase 3 trial should be able to provide an educated opinion for Darylm44's case.