The new Alzheimer's drugs are not perfect, but...

Cartoon by Megan Stewart

Many things go wrong in Alzheimer’s dementia. It’s the 50-car pileup on I-90 last month – ice, high winds, the decision to drive in bad weather. Today, we might have a cure for one of these conditions.

We have three treatment approaches.

1. Traditionally, we use drugs like donepezil, (brand name Aricept), rivastigmine (Exelon), memantine (Namenda), etc. They adjust chemicals that promote neuron communication. For some, they temporarily improve memory, thinking, behavior. Like taking ibuprofen during a cold, we may get relief from fever and aches, but the cold will run its course, regardless.

2. For behavioral issues, we use medications – antipsychotics, antidepressants, etc. – to help with sleeping, agitation, delusion.

3. New drugs. For the first time, we may be able to slow Alzheimer’s progression.

Amyloid is a natural occurring protein. When our brains make too much or fail to clear it, amyloid forms clumps in the brain. Neurons die.

The new drugs are antibodies that specifically target and remove amyloid – like a garbage collector.

In 2021, FDA approved aducanumab (Aduhelm), developed by Biogen (Cambridge, MA) and Eisai (Tokyo, Japan). It dramatically reduces amyloid clumps but doesn’t demonstrably improve memory or reasoning.

Normally at this stage, experts would say: “Do more studies. We’ll know more in 5 to 10 years.” But the FDA’s accelerated approval raised eyebrows – several FDA advisors quit in protest. An 18-month congressional investigation found the process “rife with irregularities.”   

Last December, the FDA approved a second drug by Biogen and Eisai, lecanemab (Leqembi). Based on a study of 1,800 people, lecanemab reduces amyloid clumps and improves cognition – albeit modestly.

First, let’s ignore the price tags on these drugs ($26,500 to $28,000 per year) and look at the science.

Because the study only lasted 18 months, experts must estimate long-term benefits. Best case scenario: lecanemab might delay progression from mild/moderate to severe dementia by 2.5 years. It’s progress but not a cure.

But they have some alarming side effects. I especially worry about brain swelling and bleeding.

During the study, test subjects developed temporary brain swelling (13%) and micro-bleeding (17%). But later, three subjects died of brain bleeding while taking blood thinners.

That's a problem. Blood thinners are used widely in heart diseases, strokes, and blood clots. Lecanemab now carries a black box warning about combining them. What bugs me more: Eisai has been less than forthcoming with information.

The limited success of these antibodies reinforces an important lesson: Alzheimer’s disease is a hodgepodge – heredity, injuries, lifestyle choices, heart diseases, depression, pollution, aging.

For example, many have significant amyloid clumps but don’t have dementia. By age 70, a third of the population with normal cognition have amyloid clumps on scan. We have more question marks than periods.

But in the next few years, I expect to see more studies that can identify who – and when they – benefit from anti-amyloid drugs.

A funny thing. Days ago, I went wild looking for my fat and fluffy slippers. My husband found them on top of the onions in the cupboard. (I’m convinced he was a bloodhound in a previous life.) Me? I’ve got excuses.

For my fellow If-I-remember-where-I-saw-it-last-I-wouldn’t-be-asking-you-ers, if I could offer one piece of brainy advice: Get enough sleep. During sleep, specialized brain cells clean up toxins and debris while happy neurons socialize and connect. It works. And it costs us – and Medicare – nothing.

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Volume 15, Issue 1, Posted 9:59 AM, 01.17.2023