Which means, the more things change, the more they stay the same. The big change in the Alzheimer’s disease world – which you’ve all heard about, no doubt – is that the FDA granted emergency use authorization to aducanumab, now to be named Aduhelm. That happened on the 6th of June. The FDA’s decision elicited a wide range of boldly-stated reactions, ranging from “at long last there’s hope for a treatment that might really work” all the way to “the FDA is failing the American people.”

My personal view is that the situation will stay pretty much unchanged. At best, the progression of dementia in patients who already show signs may be slightly slowed.

The history of aducanumab goes back a considerable way. It was most recently in the news back in March of 2019, when Biogen and Eisai announced that they were ending the Phase 3 ENGAGE and EMERGE trials of aducanumab in early AD, because an early analysis had demonstrated that the two trials had no chance at all of meeting their primary endpoints. These endpoints were the slowing of cognitive decline as measured by a widely used test called the Clinical Dementia Rating Scale – Sum of Boxes.

This was bad news indeed, not only for Alzheimer’s patients (and their loved ones, of course), but also for Biogen in particular.

Prior to that flop, the Alzheimer’s treatment community had had pretty high hopes for aducanumab. This was based on its mechanism of action, which was that it reduced accumulation of amyloid beta (Aβ) in the brain. And amyloid beta is one of the potential causes of Alzheimer’s, since it is thought to interfere with the transfer of information across synapses in the brain.

Both the ENGAGE and EMERGE studies found that aducanumab was effective in removing Aβ from the brains of the subjects in the studies. In formulating aducanumab, Biogen had ratcheted up the potency, and on average, the subjects had about a 30% reduction in Aβ as measured by PET scans. Likely in consequence of the increased potency, about 40% of the study subjects also experienced painful brain swelling.

Then, in October of 2019, Biogen announced a new analysis based on previously unavailable data. This analysis showed that subjects in the EMERGE study taking aducanumab experienced somewhat slower cognitive decline than placebo subjects. The difference attained statistical significance, but the difference between aducanumab and placebo subjects was quite small – a fraction of a point on an 18 point scale.

Biogen performed the same analysis on the ENGAGE study, but on this analysis aducanumab demonstrated no benefit at all in terms of cognitive decline.

The FDA’s authorization of aducanumab was based on the evidence of its capacity to reduce the Aβ burden in the brain, but it was clearly influenced by the hopeful (although slim) data supporting the clinical benefit of the drug. The FDA’s authorization was conditional; in order to continue the marketing of aducanumab/Aduhelm, Biogen will need to complete a large clinical trial confirming that removing the plaque has real cognitive benefits. If that trial fails, the FDA retains the authority to rescind the authorization.

The FDA’s authorization of aducanumab was in direct contradiction to the conclusion of its relevant advisory committee. In November of 2020, the FDA’s Peripheral and Central Nervous System (PCNS) Drug Advisory Committee had voted 10-0 against granting approval to aducanumab based on the data presented. The Committee noted that the positive results seen in one of two identical phase III studies of the Biogen anti-amyloid drug cannot be considered alone, but must be taken together with the twin study, which was clearly negative.

“This analysis seems to be subject to the Texas sharpshooter fallacy, where someone first fires a shot at a barn then paints a target around the bullet hole,” said panelist and biostatistician Scott Emerson, MD, PhD, of the University of Washington in Seattle.
A major concern about aducanumab’s approval is its price. The drug would be given monthly by infusion, and the estimated price is about $56,000 per year. It has been estimated that if just one-third of the eligible patients with Alzheimer’s disease were prescribed aducanumab/Aduhelm, the cost to Medicare would be about $112 billion per year, which is far more than Medicare spends on any other medication. If all 5.8 million Medicare-eligible adults with Alzheimer’s took the drug, it would cost $334.5 billion — or nearly half the budget of the entire Department of Defense.

The cost to Medicare is of considerable concern. Healthcare professionals have expressed worries that Medicare would seek to compensate for the huge price tag for a dubious treatment for a fraction of Alzheimer’s patients by cutting back on the approved coverage on a range of other treatments for patients with other conditions. Medicare’s purse is not infinite.
FDA watchers also point out that even if aducanumab’s Phase 3 studies, required by the FDA, fail to show meaningful clinical benefit in persons with Alzheimer’s disease, the likelihood that the FDA would really pull back their approval is not very high. Once there is a body of physicians who have been routinely prescribing aducanumab/Aduhelm, and a body of patients who have routinely been taking the drug, it will be very difficult for the FDA to pull back the approval.

Another concern is that the makers of some of the other drugs that similarly reduce amyloid beta would press the FDA to approve their drugs, based on the same reasoning as the approval of aducanumab. For example, on June 22, Eli Lilly petitioned the FDA for approval of their drug donanemab, which had been demonstrated to reduce Aβ, but had no impact on Alzheimer’s symptoms. Other drug makers are sure to follow suit.

As we might expect, the Alzheimer’s Association has a somewhat different view. In an interview, the CEO of the association said the following:

“We came to the conclusion that the science was sound for what is a very large population of people who have not had treatment. Now, clearly, this is not a cure, and it is a marginal difference for people, but a marginal difference can make a real difference for people who have only the devastation of Alzheimer’s to look to. So looking at all the science, looking at all the impact, we chose to strongly endorse approval.

“We want people to understand that it can make a difference for them, but we don’t want them to think it is going to absolutely change their course. But it is the first treatment that targets the underlying disease, rather than just symptoms. So we’ll be working with people to have them understand that. The patient community — persons with dementia and their caregivers — are excited to have something that can make a difference in their lives.

“The successful trial — and there was a successful trial — showed 22% improvement in what is effectively the cognitive functional side of people’s lives. FDA ultimately approved on what is the amyloid clearance, but the trial showed that for people with mild cognitive impairment due to Alzheimer’s disease or first-stage Alzheimer’s dementia, that it can make a difference. And that difference for people who otherwise are going to decline is real.”

The controversy continues. Two committees in the US House of Representative are launching investigations into possible inappropriate connivance between Biogen and the FDA persons who were involved in the aducanumab/Aduhelm approval process. A joint statement by House members Carolyn Mahoney and Frank Pallone Jr said “We have serious concerns about the steep price of Biogen’s new Alzheimer’s drug Aduhelm and the process that led to its approval despite questions about the drug’s clinical benefit. We strongly support innovative treatments to help the millions of Americans who suffer from Alzheimer’s disease, but Aduhelm’s approval and its $56,000 annual price tag will have broader implications for seniors, providers, and taxpayers that warrant close examination.”
And, by the way, the Alzheimer’s Association has stated that Biogen’s proposed price for Aduhelm is “unacceptable.”

The most recent developments in the saga are that on Thursday, 8 July, the FDA updated the Aduhelm prescribing information narrowing who should receive the drug, stating that aducanumab should be initiated in Alzheimer’s patients with “mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.”

And then, on Friday, 9 July, the head of the FDA called for an investigation into the approval process. Acting Commissioner Janet Woodcock said “There continue to be concerns raised regarding contacts between representatives from Biogen and FDA during the review process, including some that may have occurred outside of the formal correspondence process. To the extent these concerns could undermine the public’s confidence in FDA’s decision, I believe it is critical that the events at issue be reviewed by an independent body such as the Office of Inspector General in order to determine whether any interactions that occurred between Biogen and FDA review staff were inconsistent with FDA policies and procedures.”

Implications of the aducanumab/Aduhelm approval

I should have said “qualified approval.” One implication is that it neither proves nor disproves the theory that the presence of amyloid beta is the chief causative factor in Alzheimer’s. Yes, the reduction in the accumulation of Aβ in trial subjects taking aducanumab was linked with slightly better cognitive scores than in the subjects whose Aβ accumulation was not diminished. The most one could say about the effectiveness of the drug was that it slowed cognitive decline just a bit. It would be fair to conclude that Aβ has something to do with Alzheimer’s dementia, but it’s evidently not the single cause.

A major hope for the aducanumab trials is that it would give a boost to research on other agents that target Aβ. The most prominent agents in that space are the BACE inhibitors. Aducanumab is a BACE inhibitor, and might be said to be the last survivor of that group of drugs, most of which so far have turned out to be duds.

It’s worth a couple of paragraphs to look into the mechanism of these BACE inhibitors and how they might help to clear our brains of this Aβ clutter.

We now know that our brains normally contain considerable quantities of a substance called amyloid precursor protein (APP). It is not inside the neurons, nor yet in the dendrites extending from the neuron, but in the spaces between the dendrites, across which the signal from one neuron is transmitted to another neuron. The signal is in the form of a neurotransmitter, usually a chemical that passes through the dendrite, across the synapse, is received by another dendrite, and travels to a receptor neuron. Our brains contain billions of neurons; each neuron can have as many as hundreds of thousands of dendrites, and the total number of synapses in our brains is thought to be in the neighborhood of a hundred trillion.

And in all of those synapses there is amyloid precursor protein, a portion of which contains the amyloid beta peptide sequence. This is true of all normal, well-functioning synapses. What happens in the formation of the particular toxic plaques that (perhaps) result in Alzheimer’s is that enzymes cleave APP, leaving the amyloid beta (Aβ) segments. Two protease enzymes take part in this process – beta (β) secretase and gamma (γ) secretase. β-secretase (BACE) does the bulk of the work, and γ-secretase applies the finishing touches.

It now appears that there are two versions of Aβ. One is a sequence of 40 amino acids; the other one is just two amino acids longer. These are now labeled Aβ 40 and Aβ 42. The ratio of Aβ 40 to Aβ 42 in plaque is usually about 9 to 1, but there is evidence suggesting that when the proportion of Aβ 42 increases, the toxicity of the plaque increases. Increased quantities of the Aβ 42 peptide appear to shift the behavior of the entire Aβ pool towards obstruction the transmission of information across synapses – in other words, towards dementia.

A class of agents that showed early promise, but has since been disappointing, targets BACE, the enzyme that cleaves amyloid precursor protein (APP), thus resulting in Aβ accumulation in the synaptic space between neurons, and inhibiting the transmittal of neurotransmitters across this space. Since the transmittal of neurotransmitters from one neuron to another essentially constitutes brain activity, Aβ accumulation preventing this activity has been considered to be, if not the, at least an, essential cause of AD. Several agents inhibiting the action of that enzyme have been in various stages of development for a number of years.

Most of these agents are in a class called monoclonal antibodies (mAbs), and they are derived from various sources. Researchers identify antibodies that have emerged in response to various challenges, some in mice (murine) or other animals, some in humans. These antibodies are then cloned and produced in the laboratory. The process of creating mAbs is basically the same whether the antibodies are in response to an immune process, as in rheumatoid arthritis, to a cancer, or, in the case of AD, to the enzyme that does most of the work of cleaving Aβ from the precursor protein.

However, there is a problem with the entire mAb class: the difficulty these molecules have in passing the blood-brain barrier. For example, the crenezumab molecule is huge – it consists of about 20,000 atomic units, with a weight of 144.88 kiloDaltons. As a result, the concentration of the antibodies within the brain is only about 0.1% of the concentration in the serum – or, to put it another way, to get enough concentration in the brain, the serum concentration has to be about 1000 times higher. This invariably entails a risk of adverse effects, so researchers are understandably highly reluctant to escalate the dose. No one at this point can be certain that beta-secretase does not play significant roles elsewhere in the body, so huge doses of any BACE inhibitor may be chancy.

The failure of the Aβ-targeted therapies by itself does not mean that the amyloid hypothesis is null and void. However, it is by now clear that reducing the formation of more Aβ plaque, once the disease process is underway, will have only a limited clinical effect.

What is the current status and impact of Alzheimer’s disease?

Here’s an overview as of mid-2021:

• 6.2 million persons in the US are currently diagnosed with AD. That’s diagnosed with AD; an equal number are thought to have undiagnosed AD, perhaps in the early stages.
• This includes nearly a quarter of a million persons under 65 years of age.
• One in nine people 65 years old or older has Alzheimer’s dementia. That percentage increases with age; 36.4% of people 85 years old or older have AD.
• Almost two-thirds of Americans with AD – 3.6 million – are women. The chief reason for this large imbalance is that women’s life expectancy is about 5 years greater than men’s life expectancy, and it’s in those 5 years that the incidence of AD increases steeply.
• AD prevalence is expected to increase as our population ages. By 2030, 8.5 million Americans are predicted to have AD, and by 2050, the number is predicted to be 16 million.
• The prevalence of AD and other dementias is about twice as high in African Americans and about one-and-one half times as high in Hispanic Americans as it is in non-Hispanic whites. The reasons for this are not entirely clear. The disparity is not thought to be due to genetic differences, rather to higher prevalence of conditions and circumstances which contribute to AD and dementia.
• According to the Alzheimer’s Association, the 2021 costs to the nation associated with AD will be about $355 billion. About half of this cost will be paid by Medicare, and another significant chunk by Medicaid. Unless there is a treatment breakthrough, total costs may reach $1.1 trillion by 2050.
• Annual Medicare costs per patient with AD are estimated to be $26,358. Out-of-pocket costs are $11,571. For patients without AD the cost estimate is about $7,500.
• These costs don’t figure in the huge economic impact of AD on caregivers, who are often the immediate family members of the person with AD.
• AD is the 6th leading cause of death in the US.
• The death rate in the 5 other leading causes of death in the US – breast cancer, prostate cancer, HIV, and especially heart disease and stroke,– have declined since the year 2000, while the death rate from AD has increased by 145.2%. At present, there is no cure, and the most effective treatments do nothing to stop the progress of the disease. At best, they slow it. This, may I note, is not unlike some cancer treatments that have been deemed moderately successful.

One would think that with a huge and growing threat like Alzheimer’s, there would be a great deal of research to attempt to find effective treatment options. But, comparatively speaking, there isn’t. Currently (according to PubMed, which is part of NIH and tracks clinical trials) there are 9,795 clinical trials going on about Alzheimer’s disease treatment. Sounds like a lot? In contrast, there are 100,228 clinical trials in progress about cancer treatment. In case you didn’t pay attention to those confusing numbers, that’s ten times as many trials in cancer treatment than in Alzheimer’s.
Why might this be?

Perhaps it’s because Alzheimer’s mostly affects older folks. It’s intuitively okay to accept AD as a natural consequence of aging, whether or not it’s an accurate assessment. As I see it, the prevailing view of AD separates the symptoms, primarily dementia, from the underlying causes, whether those might be the notorious amyloid beta (Aβ) or tau protein tangles, also called neurofibrillary tangles, or something entirely different. Essentially, the people working on Alzheimer’s have come to realize that those underlying causes can appear many years before any symptoms of dementia manifest themselves. Another complication emerges, notably that many elderly people (and many not so elderly!) exhibit traits of forgetfulness entirely unrelated to AD.

The result is that by the time a diagnosis of AD based on symptoms is firmly established and other forms of dementia are ruled out, it appears that Alzheimer’s dementia may be irreversible. The brain is already severely clogged with amyloid beta or tau protein tangles, or possibly both, and there are no handy brain-clearing instruments or substances.

The situation is further complicated by the reluctance of people to undergo procedures that might lead to a diagnosis of Alzheimer’s, whatever these procedures might be. Indeed, if a diagnosis of AD does not lead to a course of treatment that significantly improves the symptoms, why would anyone be willing to be subjected to diagnosis? The outcome of the diagnostic procedure is certain to be bad news. In the case of a positive diagnosis, it’s “Yes, you have Alzheimer’s disease, but we can’t do anything to stop it.” And if the diagnosis is negative, it’s “No, you don’t have Alzheimer’s disease. You’re just an old-timer who is losing his marbles.” A lousy verdict either way.

In contrast, diagnostic procedures to detect many of the most common deadly diseases or conditions are downright attractive. Women don’t regard mammograms as pleasant experiences, but since mammograms have become widely accepted procedures (at least in most of the developed world) breast cancer mortality has plummeted. The same relationship holds true for many diseases. Most people accept these diagnostic procedures with a relatively optimistic frame of mind: if the outcome is positive – for example, the patient really does have breast cancer – effective treatment is available. And if the outcome is negative – no sign of breast cancer – it is received as good news. That is not the case with attempts to diagnose Alzheimer’s disease once it has taken hold, since at this point there are no clear treatment options that will prevent disease progression.

Are there factors linked with Alzheimer’s and dementia that could be modified?

There definitely appear to be. A few years ago a lengthy Lancet paper appeared that assessed what they termed “Population Attributable Factors” (PAFs) which they thought were responsible for a significant fraction of the incidence of dementia. The study was based in part on observation of about 10,000 adults in the UK. According to the authors, an important concept in slowing down dementia is a factor that they call “cognitive reserve.” This sounds fairly obvious – if you have more reserve of any faculty, including cognition, you can afford to spare more of that faculty than a person that has less of it to start out with.

The factors that they identified included poor education (i.e., no schooling beyond 11th grade), hearing loss, hypertension, obesity, smoking, depression, physical inactivity, social isolation, and diabetes. It’s highly likely that a number of those risk factors overlap; for example, high-school dropouts are far more likely to be smokers than are college graduates, and hypertension, obesity, physical inactivity, and diabetes certainly do tend to go together. Other data, by the way, tend to corroborate the Lancet conclusions, e.g., a 19% increase in midlife obesity in China was accompanied by a similar increase in the incidence of dementia. Cause and effect? Coincidence?

The Lancet authors estimated that a bit more than one-third of all dementia cases were caused by these Population Attributable Factors and thus were theoretically preventable. Of course, some of the changes would have to be instituted fairly early in life, such as education past 11th grade and smoking cessation. And, ideally, cognitive reserve should be acquired from the start.

You will have noticed that most of those factors are closely linked with overall lifestyle – a healthy diet and exercise should help prevent dementia, including Alzheimer’s dementia. (The one exception might be hearing loss, although some of that might be attributable to listening to pounding rock music.)

In terms of diet, perhaps the strongest evidence relates to some antioxidant nutrients, including in particular vitamin E and vitamin C, which have been shown, at least in animal studies, to protect the brain from damage due to inflammatory and oxidative mechanisms. Three prospective human studies assessed the relationship between those nutrients and the risk of Alzheimer’s disease – one in Chicago, one in Rotterdam, and one in New York City. The Chicago and Rotterdam studies found a significantly lower risk of Alzheimer’s in individuals with a higher intake of vitamin E; the New York study did not find that association, but it happened that the vitamin E intake in subjects in the New York study was very much lower than in the Chicago or Rotterdam cohorts, so that may have accounted for the difference. The relationship between vitamin C intake and Alzheimer’s was much less robust than with vitamin E; only the Rotterdam study found a link.

It needs to be emphasized that none of those studies found a link between vitamin E and vitamin C supplements and a reduced risk of Alzheimer’s. To the extent that a reduced risk was detected in relationship with vitamin E intake, it was only as a result of the presence in the diet of foods that were rich in vitamin E. A possible reason for the absence of beneficial effect with vitamin E supplements is that those supplements usually consist only of alpha-tocopherol; however, gamma-tocopherol is more abundant in the diet, and it has been suggested that the combined intake of all eight forms of tocopherol reduce oxidative stress and inflammation more than alpha-tocopherol alone. We are told that the foods richest in vitamin E are vegetable oils, nuts (especially almonds), seeds, and also whole grains, eggs, and some fruits and vegetable such as avocados, apples, and melons.

Dietary fats, especially transfats, may significantly increase the risk of Alzheimer’s, but the evidence concerning fats in general is somewhat contradictory. It’s intuitively apparent that cholesterol in the vascular system in the brain cannot be good for cognition, and a study in Japan showed a strong relationship between cholesterol levels and the deposition of amyloid plaques in the brain. The study followed 147 adults for up to 15 years before their deaths, and then performed autopsies on their brains. Those whose total cholesterol levels were more than 224 mg/dL were seven times more likely to have amyloid plaques than those whose total cholesterol was below 173 mg/dl. The link between elevated LDL-cholesterol, greater than 155 mg/dL and amyloid plaque was even more robust, by a factor of eight, over those whose LDL-C level was below 106 mg/dL.

Omega-3 (Ω-3 )fatty acids may also reduce the risk of AD-related dementia, in particular docosahexaenoic acid (DHA) which happens to be a major component of membrane phospholipids in the brain. Patients with established AD have been found to have lower levels of Ω-3 fatty acids than the general population, and one fish meal per week was associated with a 60% lower risk of developing AD in both the above-mentioned Rotterdam and Chicago studies. However, as with the vitamin E and C supplements, no studies to date have found an association between fish-oil capsules and a lower risk of developing AD. You actually have to eat the fish!

The findings regarding vitamin E, cholesterol, and fish, and their association with AD-related dementia certainly support the general recommendation of a Mediterranean diet, with its emphasis on fish, vegetables, fruit, grains, and olive oil, as per the Lancet paper’s conclusions.

Would detecting Alzheimer’s before dementia symptoms appear make a difference?

My answer would be yes. For one, there is definitely a possibility that treatment options will become available that, if initiated early enough can significantly slow the progression of dementia symptoms. Up to now, drugs have been evaluated in persons who are already showing Alzheimer’s symptoms. This was the case in the aducanumab trials. The subjects were already experiencing cognitive decline; the trial was to see whether the drug would slow the progression of cognitive decline, but the process was already underway. But what if a study population could be enrolled that was not experiencing cognitive decline, but was likely to do so in the relatively near future?

A study published in Nature Magazine on 24 May 2021 described a simple blood test that, coupled with standard brief memory tests, predicted who would develop Alzheimer’s with a high degree of accuracy. The study subjects in this study had not developed cognition deficits but were exhibiting memory complaints similar to those experienced by many (if not most) seniors. The blood test assayed phosphorylated tau (p-tau), the APOE4 genotype, and scores from two ten-minute executive function and memory tests. The test was able to predict the onset of Alzheimer’s disease onset within the next 2 to 6 years with 91% accuracy. In comparison, when dementia experts examined the same subjects, they were able to predict Alzheimer’s with about 71% accuracy. (Palmqvist S. Nature Magazine 2021;27:1034-1042)

There have been previous attempts to design a test that would reliably identify persons at risk for developing Alzheimer’s. Doc Gumshoe described such a test in an epistle on October 2, 2019. That test was a bit less accurate than the one described above, but the principal difference is that it required highly precise measurement of the diameter of phosphorylated tau and insulin receptor substrate particles. It could not be described as a simple test, whereas the test described in Nature Magazine is simple enough that it could be quite widely administered.

Could that test be included as part of the annual physical examination that many of us regularly take as a way of preserving our health? I can’t imagine that many people would voluntarily seek out a test to predict their chances of developing Alzheimer’s, because of the perception that there’s not a whole lot they could do about it if the results of the test were that Alzheimer’s was on the way. On the other hand, if the tests for tau and the APOE4 genotype could be routinely included in the blood test, and if the examining physician could include just a few quick questions to test memory and cognition, this might lead to significant differences in the outcomes of individual patients.

Exactly how would this make a difference, if there are no drugs that have been demonstrated to make a real difference in the development of Alzheimer’s?

Here’s where those Population Attributable Factors come in to play. Supposing that our sample subject is a woman in her 50s who was predicted to be at risk for developing Alzheimer’s. What could she do?

Well, obviously at that time in her life, we can’t tell her she has to stay in school past 11th grade. But she might do the equivalent – engage in activities that require the use of her wits. She might be given even more reason to adopt the healthy life-style behaviors included in those PAFs. She should take care to preserve her hearing – turn the volume down when she listens to rock on her earbuds. Keep in touch with her friends, stay both physically and mentally active, don’t smoke, watch her weight …

That no doubt sounds like the bland recommendation that every conscientious MD makes to most patients. But if those recommendations are linked with pretty good evidence that a certain group of factors are strongly linked with a condition that everybody dreads, there’s a chance, at least, that those recommendations might be taken up.

A bit of good news

Researchers at the NYU Grossman School of Medicine investigated a technique that reduced levels both of Aβ and toxic tau by as much as 59% in the brains of monkeys. They were treated with CpG oligodeoxynucleotides, which prompted immune defense cells to attack those substances as well as misshapen proteins. The removal of Aβ and toxic tau was accompanied by improved cognition in elderly monkeys, who were able to perform on a series of puzzles just as well as younger monkeys and much better than elderly monkeys which had not received that treatment. (Wisniewski T. Aging Neurosci 2020 Mar 3;12:36)

That calls to mind the drug I mentioned in a previous piece: fasudil, which aids a process called autophagy, where our immune cells remove unnecessary or dysfunctional materials in our system, such as the stuff in our brains that leads to Alzheimer’s. Fasudil is currently in a clinical trial in patients with Alzheimer’s.

We’ll keep an eye on both of those, and whatever else is going on.

*****

This is the ninth Doc Gumshoe piece about Alzheimer’s. As much as I try to make each new piece different and, dare I say, interesting, they all more or less fall into the same pattern. There’s something about the current status of Alzheimer’s, some news about how some treatment options have fared in clinical trials, and a hint of something promising. All too often, the supposedly promising treatment options turn out to be disappointing. To put the Alzheimer’s situation in perspective, consider that cancer research has made huge advances, such that what’s in the news these days is that there are reasonably effective treatments for cancers for which there was no hope of treatment a few years ago. And as for heart disease, the fatality rates are way, way down.

Will we see similar successes with Alzheimer’s? Doc Gumshoe ventures a positive view: if we can intervene early enough in the disease process, we may be able to stop progression. I hope I am not being too optimistic. Best to all, and keep those comments coming! Michael Jorrin (aka Doc Gumshoe)

[ed. note: Michael Jorrin is a longtime medical writer (not a doctor), who I dubbed “Doc Gumshoe” many years ago — he writes health and medicine-focused columns for our readers a couple times a month, and though he does not generally cover investment ideas he has agreed to our trading restrictions. You can find his past columns here.]