Second Opinion | Remembering forgetting could be a good sign


Hello and happy Saturday! Here’s this week’s round-up of eclectic and under-the-radar health and medical science news.


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Forgetting where you put the keys? Can’t remember names? Is it the first sign of dementia?

That might depend on whether you remember that you’re forgetting things. And whether your caregivers are more worried about your memory loss than you are.

“It seems that when caregivers see it as more problematic than patients then it’s predictive of whether or not people go on to develop dementia,” said Dr. Philip Gerretsen, a clinician scientist at the Centre for Addiction and Mental Health in Toronto.

Using brain imaging data and other clinical information from more than 1,000 patients with early cognitive decline, his new study suggests there’s a relationship between a person’s level of awareness of memory issues, and their risk of future disease.

Some of the people studied thought they were having memory issues, but their caregivers weren’t convinced. And those people didn’t end up developing dementia.

“Most intriguingly it’s the patients that seem to be hyper-aware of having some cognitive problems relative to their caregivers that actually don’t go on to develop dementia,” Gerretsen said, adding that those people might be suffering memory loss for other reasons, including anxiety or depression.

Gerretsen believes there might be clues to dementia in the region of the brain that controls disease awareness, a condition called “anosognosia” — a neurological term for not knowing that you’re sick.

“The most interesting thing is anosognosia, or illness awareness, is really under-studied and what we’re seeing is that it’s an independent predictor of going on to develop dementia when people complain of memory issues.”

Gerretsen says there’s a suggestion that Alzheimer’s disease might be affecting the brain regions involved in illness awareness. His next study will investigate whether brain stimulation methods can improve those underlying brain structures, which in turn might help slow down the progression to dementia.

Death of a ‘good cholesterol’ idea

The theory was beautiful. If lowering bad cholesterol reduces heart attack risk, (and it does, as the statin drugs have shown) then raising good cholesterol should do the same thing.

Scientists even knew how to do it by interfering with a blood protein called CETP (cholesteryl ester transfer protein.) Because the CETP is involved in turning good cholesterol (HDL) into bad, (LDL) then a drug that blocked the protein should cause good cholesterol to rise.


The demise of a promising hypothesis about ‘good’ cholesterol. (Shutterstock)

It worked, setting off a pharmaceutical race that had industry analysts predicting the next blockbuster drugs.

But optimism faded when the first CETP inhibitor had unintended off-target effects that actually increased heart attacks. Pfizer immediately abandoned the drug. That was 2006.

By 2015, two more companies had dropped their CETP programs after the drug failed to improve cardiovascular outcomes.

Analysts finally called the hypothesis officially dead this week when Merck announced it would not be submitting its CETP drug for market approval.

So what went wrong? Human physiology once again proved to be devilishly complicated. It’s more proof that using drugs to change surrogate biomarkers (indicators that doctors measure with lab tests) doesn’t always translate into better health. In this case, it turns out that simply raising good cholesterol, by itself, does not prevent heart attacks, strokes or death.

It’s no surprise to Dr. Dennis Ko at the Institute for Clinical Evaluative Sciences in Toronto. After studying data on more than 500,000 Ontario residents, Ko showed that high levels of good cholesterol alone didn’t predict good health.

The data revealed that people who have low levels of good cholesterol also have other problems, including low income and unhealthy lifestyles. Ko concluded that simply increasing the HDL without addressing those other factors will not by itself improve heart health.

“I think most people have changed their minds about HDL cholesterol in terms of whether we can change the levels to dramatically improve cardiovascular outcomes,” Ko said.

So what’s the message for people obsessed with their cholesterol levels?

“I would probably worry less about the HDL levels,” Ko said, adding if it’s very low, it might be a marker of poor health and efforts to improve lifestyle would be the most beneficial thing.”

‘Life finds a way’ as malaria mosquitoes win 1st round in gene drive battle

A “gene drive” is a tool scientists are developing to spread new genetic traits rapidly through a population.

Ever since the CRISPR gene editing system made it possible to easily and cheaply manipulate DNA, scientists have been tinkering with gene drives as a way of controlling disease-carrying mosquitoes.

The idea is to genetically alter the mosquito genome to weaken its reproductive system and then spread that change as fast as possible through new generations of insects.

Malaria mosquito

Nature fought back when scientists attempted to manipulate the DNA of malaria mosquitoes. (James Gathany/CDC)

But as usual, nature has a way of deflecting human interventions. And it seems mosquitoes won the first round in the gene drive battle, according to a new paper published in PLOS Genetics.

Scientists at Imperial College London used CRISPR to engineer a weakness in the female malaria mosquito’s reproductive system so there would be fewer offspring. They then introduced that genetic weakness to a caged population of mosquitoes.

The gene drive spread rapidly in just four generations of insects. But after 25 generations the scientists noticed that it slowed down as new mosquitoes developed a genetic mutation that fixed the flaw and restored their reproductive rate.

Despite the resistance, lead scientist Tony Nolan called the experiment a success, saying it’s the first ever proof in principle for a gene drive designed to reduce mosquito populations.

Now they’re going back to the lab to tweak the gene drive and come up with ways to overcome the resistance problem, presumably not at all deterred by the prophetic words of Dr. Ian Malcolm (actor Jeff Goldblum) from the movie Jurassic Park:

“Life..uh..finds a way.”

Currently there are no gene drive programs being used outside the lab.

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