The Brain and Aging
One of the troubling by-products of growing old is dementia — an estimated 44 million around the world now suffer
from it. Some estimates say 160 million people worldwide
could be afflicted by 2050, with more than 7. 7 million
new cases reported globally each year (that’s about one
new case every four seconds). The numbers are daunting, as is the image of Julianne Moore in the movie Still
Alice. Billions have been spent on research and clinical
trials, but many unanswered questions remain. One
thing we know for sure: aging causes dementia and cognitive decline. And Alzheimer’s is on the rise; 5. 3 million
Americans now have the disease.
“The reality is that 15 percent of us in America will get
Alzheimer’s,” says Dr. Dale Bredesen, an internationally
recognized expert in neurodegenerative diseases and
founding CEO of the Buck Institute. So of the 300 million
living in the U. S., 45 million will develop Alzheimer’s disease (AD) — it’s just that most people are simply too young
to know it yet, Bredesen says.
So what do we know about this progressive brain dis-
order that slowly destroys memory and thinking skills
and has historically been irreversible?
Scientists are discovering that age-related changes in
the brain such as atrophy, synapse loss and free radicals
may contribute to AD, as does genetics. Apolipoprotein E
(ApoE), a cholesterol-carrying protein that transfers fat,
is also involved in AD. It’s encoded by the gene of the same
name. “This gene has several forms but it’s ApoE4 that’s
troublesome,” says Bredesen’s colleague Ram Rao, a Ph. D.
and associate research professor at the Buck.
Apparently, about two-thirds of people with AD carry
ApoE4, and women who carry the gene are more likely to
get AD than men are. The gene is also linked to formation of
the amyloid-beta peptide associated with sticky plaque, one
of the supposed hallmarks of the disease, but how ApoE4
actually brings or heightens risk for the disease is unclear.
Even though ApoE4 is considered a major genetic risk fac-
tor for AD, Rao doesn’t recommend rushing out to get tested
for it: “Having one or t wo copies of the ApoE4 gene does not
mean that an individual will develop Alzheimer’s disease.
Similarly, not having the ApoE4 gene does not guarantee
that the individual will not have the disease.” That’s the case
even with a family history of Alzheimer’s disease, he says.
“Furthermore, testing for this gene would be more prob-
lematic,” he adds. “It could cause unwarranted fear, worry
and anxiety about getting the disease. Genetic tests are of
value only in a research setting. Instead, I would advocate
for anyone above 50 to do all the (recommended) lifestyle
interventions irrespective of their ApoE4 status” — everyday regimen changes
that can help prevent cognitive decline (see sidebar).
What’s more, says Bredesen, studies he’s involved in through the
UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the
Buck Institute suggest cognitive decline can be reversed. That will take
a broader-based treatment rather than searching for a single drug with
a single target, the research suggests. Tackling or preventing cognitive
decline requires changes in factors like diet, exercise, stress exposure,
sleep, brain stimulation and vitamin intake. AD sufferers commonly have
insulin resistance, vitamin D abnormalities, inflammation issues, and hor-
monal imbalance, Bredesen says. “I tell people, ‘Now that you are having
problems with your memory, we are going to treat you like a competitive
athlete.’ We want people to be optimal, not just normal.”
One of the first recommendations for patients with cognitive decline
is exercise, which can slow the progression, alleviate depression,
improve quality of life and even help prevent AD itself. Diet also plays
a big role. In fact, Bredesen says, the fastest track to Alzheimer’s would
be eating a ton of sugar to spike your insulin; gobbling up trans fats,
simple carbs, processed foods and beef with hormones; and avoiding
vegetables and fruits — and to drive the nail in the coffin, be sure to
drive everywhere and get no exercise. Other risk factors include poor
hygiene, high stress and lack of sleep.
“There’s also a window of 10 years from first symptoms until we can
no longer reverse it,” he adds. If AD is detected early on, there’s still time
to counteract detrimental effects. But most people arrive at a clinic with
symptoms when they’re beyond that 10-year window.
Meanwhile, researchers at the Queensland Brain Institute have shown
that noninvasive ultrasound can restore memory in mice with AD, by
breaking apart the neurotoxic beta-amyloid plaques in the brain they
think cause cognitive decline. Sound waves opened the mice’s blood-brain
barrier and stimulated microglial (waste-removal) cells to eradicate the
beta-amyloid clumps. Memory function was fully restored in 75 percent of
the mice without damaging brain tissue. The study’s co-author, Professor
Jürgen Götz, believes this method could “revolutionize Alzheimer’s treatment.” The Australian team hopes to scale the treatment to higher animal
models such as sheep and then conduct human clinical trials.
But Rao questions whether such technology can be replicated in more
complex animals or people. “Until now, nearly all of the rodent findings
could not successfully be translated in humans,” he notes. “When it comes
to exposing the human brain to ultrasound waves (even at low intensity),
there are safety concerns. There is always a danger of triggering a massive
immune reaction or causing brain hemorrhage. Besides, AD researchers
are still unsure whether eliminating beta-amyloid deposits (by any type
of intervention) is the key to treating or stopping Alzheimer’s.”
Of the 300 million living in the
U.S., 45 million will develop