Good months, bad months

When people are interested in my story, and when they ask me how I'm doing, I say that people in memory care tend to have good days and bad days.  I, on the other hand, have good months and bad months.  Fortunately, I'll have a string of good months before encountering a single bad month.

What's a bad month like?  Well, the worst part about one is how scary it is.  I'm afraid of returning to the dark days of 2015 and early 2016.  I begin having brain hiccups of the type I was having back then, such as an inability to remember to lock my car.  I may be reminding myself to lock the car as I pull into a parking stall, but when I come back out of the store it's unlocked.  This could have unfortunate results with car prowls on the rise.

I may also have a return of the episodes of depression I described in Beating the Dementia Monster.  These are relatively mild, and they only last into the evening.  They may be a very mild form of "sundown syndrome," but I'm not sure.  This usually appears in people with more advanced disease, and I don't display all of the symptoms.  But, who knows?  The feelings were strongest and most disruptive back when I had the most serious cognition and memory problems.

I speak in Spanish with friends in Latin America over the Internet a couple of times a week.  I began learning Spanish 13 years ago, so I'm still learning.  Or trying to learn.  During good months I can speak both fluently and fluidly, and I feel well about it.  During bad months, I'll struggle with the simplest conversation.

During bad months I'll slur my speech more than usual.  This is frustrating and a bit embarrassing to me.  But, like the other traits, this will largely pass with time.

So far, I've had no indication of the return of the phenomenon I fear the most -- impaired vision.  I had to stop driving for more than six months when I couldn't reliably see pedestrians.  For now, my driving is free of close calls, and I feel completely safe.  But I am risk averse and will stop immediately if the vision problems return.  As we found out in 2015-16, Amy can drive me, and I can take the bus.  After all, the bus is reliable and free for seniors.

Something I've noticed is that any or all of these can occur during a bad month, but they don't all come and go in unison.  I'm guessing that's because these different changes arise from changes within different parts of the brain.  The disease affects different parts of the brain differently.  I also believe that the different lifestyle changes I've made in different domains have different healing effects on different parts of the brain.  As we said in Beating the Dementia Monster, the BDNF protein does much of its work by prompting stem cells in the hippocampus to form new neurons there.  That's certainly good for memory and space-time orientation.  But what about the rest of the brain?

What prompted my to write this today?  I seem to be coming off of a "bad month."  It wasn't terribly bad, but I was slurring my speech more than usual.  I also had periods when I had trouble putting the words together for a coherent conversation.  But, as in the past, these problems seem to  be on the wane.  Interestingly, I've had no issues with memory or cognition during this period, although I usually notice them during a bad month.

The worst thing about this month has been my balance deteriorating more rapidly, but that doesn't seem to get better.  I'm not finding any doctors with great ideas about what to do about it.  Physical therapy helps a little, but its power seems to be waning.

But things are looking up.  When I wake up in the morning, I remember what happened yesterday, and I know what's on the agenda for today.  Life is good.

Biogen struggles, but there may be a bright spot

In a recent press release, Biogen noted some write-offs and other budget perturbations due to the unwillingness of Medicare to fully cover Aduhelm.  We discussed what's happening with the FDA previously, and Biogen is finding they need to begin dismantling some of the infrastructure they were building to support a larger scale operation to provide Aduhelm to patients with Alzheimer's disease.  This has hurt them financially, and they're looking for other ways to cut costs and placate stockholders.

But all is not lost.  In Beating the Dementia Monster, we discussed another Biogen monoclonal antibody treatment called BAN2401 -- also known as lecanemab.  We've also discussed it on this blog.  Biogen has received fast track authorization from the FDA to continue with the phase 3 trials of lecanemab.  If they go as well as earlier results promised, Biogen says “lecanemab has the opportunity to become the first anti-amyloid antibody to obtain full approval for Alzheimer’s disease in the U.S..”  Some of its trial results displayed better performance than aducanumab (Aduhelm), so Biogen is quite optimistic.  On the assumption that lecanemab lives up to its promise, Biogen will submit their application for full approval in early 2023.  Hopefully it will not be under a cloud as with aducanumab.

"What's good for the heart is good for the brain." So is "good cholesterol" good for the brain?

Most of us get our cholesterol levels checked every year or so.  We hope that our "bad cholesterol" (low-density lipoprotein, or LDL) values will be low and our "good cholesterol" (small high-density lipoprotein, or HDL) will be higher.  The right numbers should favor a lower likelihood of stroke or heart attack.  Great.  But what does that mean for our brains -- our cognition and memory?  What does that mean for our susceptibility to Alzheimer's disease?

Remember that the ApoE4 gene variant is the gene most strongly correlated with the "sporadic," or older onset form of Alzheimer's disease.  (The ApoE2 variant seems to be neutral, and ApoE3 actually seems to be protective for Alzheimer's.)  The purpose of the ApoE gene, regardless of the variant, is to provide for a protein that aids in the transport of cholesterol in the blood.  So there's a connection between blood cholesterol and Alzheimer's disease.

That connection may or may not be relevant to new findings reported in the journal Alzheimer's and Dementia by researchers at the USC Keck School of Medicine.  The journal article was entitled "The small HDL particle hypothesis of Alzheimer's disease."  (The research was discussed in this press release.)  The article proposed a new hypothesis regarding Alzheimer's disease, that "small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions."

So what did they do?  The researchers measured the concentrations of small HDL particles in cerebrospinal fluid (CSF) and the blood of 180 individuals ≥60 years of age.  They found a positive association between small HDL concentrations in CSF and performance in three domains of cognitive function.  The researchers controlled for ApoE4 status, age, sex, and years of education.  They also found a significant correlation between levels of small HDLs in CSF and plasma.  They specifically found that higher HDL values correlated with greater synaptic plasticity, reduced inflammation, more efficient scavaging of oxidized lipids in cerebral blood vessels. Synaptic plasticity is foundational to memory, inflammation is part of the Alzheimer's disease process, and oxidized lipids promote Alzheimer's disease.

Apparently HDL particles come in different sizes, and the small size is most commonly found in the brain.  The researchers claimed credit for being the first to actually count HDL particles in the brain.

The takeaway seems to be that there's a correlation between higher levels of good cholesterol, better memory and cognition, and resistance to Alzheimer's disease.  So this appears to be another reason to track your cholesterol and keep it in recommended limits.  Of course, diet and exercise are your best strategies for this.  As always, more research is required, but the researchers hope this will lead to finding more biomarkers for Alzheimer's and targets for therapies.  

What's the ideal amount of sleep? Popular media is buzzing.

My Mom told me that I was supposed to get eight hours of sleep at night.  Didn't every Mom say that?  And I think we also heard that in health class and from the sleep experts.  But, older people have a harder time sleeping, and I've heard people say that older people don't really need as much sleep as younger people.  That's why they sleep less.  Is that true?  And sometimes people ask me, is it bad when older people get too much sleep?  (My Mom reads all of these posts, so I may hear from her about this.)

We've mentioned before Dr. Matthew Walker and his widely respected book Why We Sleep.  Dr. Walker contends that everyone needs 7-8 hours a night, although he strongly favors the 8-hour end of that spectrum.  We've also written before that atrophy of the different parts of the brain makes it harder for us to sleep and especially to stay asleep once we've begun.  Dr. Walker says we still need to do what it takes to get our seven or eight hours in.  So just because we sleep less doesn't mean we need less -- we still need the same amount.  And failing to sleep straight through seven or eight hours in one sleep cycle encourages the buildup of beta amyloid in the brain.  That's part of the Alzheimer's disease process.

You may have seen reports of a new study on hours of sleep in middle aged and older people.  It was published a few days ago in the journal Nature Ageing.  It's entitled "The brain structure and genetic mechanisms underlying the nonlinear association between sleep duration, cognition and mental health."  If you don't want to pay $32 to download the journal article, you can read more about it here in Science Daily.  

In popular media, the study is important for telling us that the optimal sleep period for middle aged and older people is seven hours, and getting too much sleep is bad for your memory and cognition.  But didn't we already know that?  We wrote about similar findings in another study last year.  (The new study does add that disrupting your nightly sleep schedule and accumulated hours of sleep can increase problems with cognition and mental health.)

But there's actually more.

The title refers to a "non-linear association."  What's that about?  Here is a set of graphs from their data.  They relate hours of sleep to performance on a set of cognitive tests.  I recognize these tests as those that I get periodically from my neurology care team in Seattle.  You'll note that all of the curves find their optimum point around seven hours, although some peak more at seven and a half or eight hours.

Particularly interesting was the association between optimal sleep and brain structure.  Variation in the thickness of layers of cortex and the size of structures were all associated with variation in hours of sleep.  The researchers specifically found variations in the volumes of the precentral cortex, the lateral orbitofrontal cortex and the hippocampus were all associated with variations in sleep.  They referred to "damage" to the hippocampus in people who don't get the optimal amount of sleep.  Given the role of the hippocampus in memory processes and in Alzheimer’s disease, the nonlinear association between sleep duration and this brain region is of particular importance to us.

The article is telling many people something about optimal sleep duration that they probably hadn't heard yet.  That's because they don't read this blog.  But it seems the article is attracting more interest in scientific circles because it provides new insights on why seven to eight hours would be optimal.  It looked at many parts of the brain involved in memory and cognition, and it addressed how these parts are affected by varying sleep habits.

What's up with Aduhelm?

Aduhelm continues to live under a cloud.  We wrote earlier that the Centers for Medicare and Medicaid (CMM) had decided they will only cover Aduhelm treatments in the context of participation in a controlled drug trial.  In other words, to get coverage, you must be accepted into an approved trial.  This would be what the FDA calls a phase 4 trial.  It's to check "real life" performance of an approved treatment.  If it fails the trial, the FDA's original approval may be withdrawn.  Of course, CMM and the FDA are requiring the phase 4 trial because there was so much ambiguity in the results of the phase 3 trial.  That ambiguity has led many to believe the FDA should never have approved the treatment in the first place.

How long will the trial take?  The data-gathering phase itself is four years.  It could be five years before results are published and accepted.

So if someone wants to try Aduhelm, are there any phase 4 trials available?  They're starting.  Biogen has developed a protocol and will begin recruiting participants in 10 centers across the US this month for a trial code named Envision.

In other news, Biogen has just applied to the Japanese regulatory agency for approval of Aduhelm in Japan.  Hopefully, things will go better in Japan than they have been going in Europe.  As we wrote previously, the European Committee for Medicinal Products for Human Use recommended against approval of Aduhelm for use in Europe.  Biogen went back to beef up their application, but they recently gave up.  They will need better data, data which might come from the phase 4 trial in the US.

If we hear anything else, we'll let you know.