A graphic depicting a synapse, a connection between brain cells. Image: Christine Daniloff |
A
clinical trial of an Alzheimer’s disease treatment developed at Massachusetts
Institute of Technology (MIT) has found that the nutrient cocktail can improve
memory in patients with early Alzheimer’s. The results confirm and expand the
findings of an earlier trial of the nutritional supplement, which is designed
to promote new connections between brain cells.
Alzheimer’s
patients gradually lose those connections, known as synapses, leading to memory
loss and other cognitive impairments. The supplement mixture, known as
Souvenaid, appears to stimulate growth of new synapses, says Richard Wurtman, a
professor emeritus of brain and cognitive sciences at MIT who invented the
nutrient mixture.
“You
want to improve the numbers of synapses, not by slowing their degradation—though
of course you’d love to do that too—but rather by increasing the formation of
the synapses,” Wurtman says.
To
do that, Wurtman came up with a mixture of three naturally occurring dietary
compounds: choline, uridine, and the omega-3 fatty acid DHA. Choline can be
found in meats, nuts, and eggs, and omega-3 fatty acids are found in a variety
of sources, including fish, eggs, flaxseed, and meat from grass-fed animals.
Uridine is produced by the liver and kidney, and is present in some foods as a
component of RNA.
These
nutrients are precursors to the lipid molecules that, along with specific
proteins, make up brain-cell membranes, which form synapses. To be effective,
all three precursors must be administered together.
Results
of the clinical trial, conducted in Europe,
appear in an online edition of the Journal of Alzheimer’s Disease. The
new findings are encouraging because very few clinical trials have produced
consistent improvement in Alzheimer’s patients, says Jeffrey Cummings, director
of the Cleveland Clinic’s Lou
Ruvo Center
for Brain Health.
“Memory
loss is the central characteristic of Alzheimer’s, so something that improves
memory would be of great interest,” says Cummings, who was not part of the
research team.
Plans
for commercial release of the supplement are not finalized, according to
Nutricia, the company testing and marketing Souvenaid, but it will likely be
available in Europe first. Nutricia is the
specialized health care division of the food company Danone, known as Dannon in
the United States.
Making connections
Wurtman first came up with the idea of targeting synapse loss to combat
Alzheimer’s about 10 years ago. In animal studies, he showed that his dietary
cocktail boosted the number of dendritic spines, or small outcroppings of
neural membranes, found in brain cells. These spines are necessary to form new
synapses between neurons.
Following
the successful animal studies, Philip Scheltens, director of the Alzheimer Center
at VU University Medical Center in Amsterdam,
led a clinical trial in Europe involving 225
patients with mild Alzheimer’s. The patients drank Souvenaid or a control beverage
daily for three months.
That
study, first reported in 2008, found that 40% of patients who consumed the
drink improved in a test of verbal memory, while 24% of patients who received
the control drink improved their performance.
The
new study, performed in several European countries and overseen by Scheltens as
principal investigator, followed 259 patients for six months. Patients, whether
taking Souvenaid or a placebo, improved their verbal-memory performance for the
first three months, but the placebo patients deteriorated during the following
three months, while the Souvenaid patients continued to improve. For this
trial, the researchers used more comprehensive memory tests taken from the
neuropsychological test battery, often used to assess Alzheimer’s patients in
clinical research.
Patients
showed a very high compliance rate: About 97% of the patients followed the
regimen throughout the study, and no serious side effects were seen.
Both
clinical trials were sponsored by Nutricia. MIT has patented the mixture of
nutrients used in the study, and Nutricia holds the exclusive license on the
patent.
Brain patterns
In the new study, the researchers used electroencephalography (EEG) to measure
how patients’ brain-activity patterns changed throughout the study. They found
that as the trial went on, the brains of patients receiving the supplements
started to shift from patterns typical of dementia to more normal patterns.
Because EEG patterns reflect synaptic activity, this suggests that synaptic
function increased following treatment, the researchers say.
Patients
entering this study were in the early stages of Alzheimer’s disease, averaging
around 25 on a scale of dementia that ranges from 1 to 30, with 30 being
normal. A previous trial found that the supplement cocktail does not work in
patients with Alzheimer’s at a more advanced stage. This makes sense, Wurtman
says, because patients with more advanced dementia have probably already lost
many neurons, so they can’t form new synapses.
A
two-year trial involving patients who don’t have Alzheimer’s, but who are
starting to show mild cognitive impairment, is now underway. If the drink seems
to help, it could be used in people who test positive for very early signs of
Alzheimer’s, before symptoms appear, Wurtman says. Such tests, which include PET
scanning of the hippocampus, are now rarely done because there are no good
Alzheimer’s treatments available.
