Alleviating Alzheimer’s

Nutrient mixture promotes new synapse growth, improves memory

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CAMBRIDGE, Mass.—Researchers at the Massachusetts Instituteof Technology (MIT) have released results of a recent clinical trial of atreatment for Alzheimer's disease. The treatment in question is a nutrientmixture that has been shown to improve memory in patients with earlyAlzheimer's by promoting new connections between neurons. The results of thetrial appeared in the July 10 online edition of the Journal of Alzheimer's Disease.
Alzheimer's causes the loss of synapses, the connectionsbetween neurons. However, the new supplement mixture, Souvenaid, serves tostimulate new synapse growth, according to Dr. Richard Wurtman, a professoremeritus of brain and cognitive sciences at MIT and the inventor of Souvenaid.
The mixture consists of three naturally occurring dietarycompounds: choline, uridine and DHA, an omega-3 fatty acid. Choline is presentin meat, eggs and nuts, and omega-3 fatty acids can be found in foods such asfish, eggs, flaxseed and meat from grass-fed animals. As for uridine, thecompound is naturally produced by the liver and kidney and is also found insome foods as an element of RNA. The nutrients are the forerunners to the lipidmolecules that, in combination with certain proteins, comprise brain-cellmembranes, which form synapses.
Wurtman notes that synapses usually have a lifespan ofroughly six to 12 months, and the brain is constantly replacing them atessentially the same rate as they are lost. He likens the issue of synapse lossto that of a half-full bathtub, in which the drain is open and the faucet ison. Provided the output and input match, as with the loss and production ofsynapses in a healthy brain, the 'water' level remains the same. In seeking toraise the level, Wurtman notes that the options consist of plugging thedrain—stopping the loss of synapses—or turning the water on higher.
The former, he notes, is the avenue most Alzheimer's diseaseresearchers have pursued in the past, seeking to target amyloid a beta, whichis known to be associated with the disease. It could still hold promise, "butit's been kind of disappointing in the last few years because now there are atleast four different drugs that do lower amyloid, and they don't seem to helppatients," says Wurtman, which is why his research has run towards trying toincrease synapse formation in lieu of slowing synapse loss.
As for whether the use of Souvenaid can match or outpacethat rate of degradation, Wurtman notes that it such a thing cannot beprecisely measured, but it is possible to look at markers for numbers ofsynapses and see that after one week, two weeks or a month, the levels haveincreased.
He originally came up with the idea for targeting synapseloss roughly 10 years ago, and found that in animal studies, the cocktailserved to increase the number of dendritic spines, small outcroppings of neuralmembranes in brain cells which are necessary for forming synapses betweenneurons. After the animal studies, Philip Scheltens, director of the AlzheimerCenter at VU University Medical Center in Amsterdam, led a clinical trial inEurope in which Souvenaid was tested in 225 patients with mild Alzheimer's. Theparticipants drank either Souvenaid or a control beverage every day for threemonths, and the first study, covered in 2008, resulted in 40 percent ofpatients taking Souvenaid seeing improvement in a test of verbal memory, whileonly 24 percent of patients receiving the control beverage improved.
Scheltens also oversaw the new study, in which 259 patientswere followed for six months, as principal investigator. Patients in both theSouvenaid and placebo groups improved their verbal-memory performance for thefirst three months of the study, but while the placebo patients deteriorated inthe second three months, the Souvenaid patients saw continued improvement. Noserious side effects were seen. The use of EEG on patients showed that thebrains of patients receiving the supplements began shifting from dementiapatterns to those of more normal brain function, and since EEG patterns reflectsynapse activity, the researchers noted that the results suggest an increase insynaptic function after treatment.
The mixture is not effective in those with severe dementia,Wurtman notes, which was confirmed in a previous study at Rush Medical Schoolin Chicago. By the time dementia is particularly advanced, the brain is smalland patients have lost many neurons, and as such cannot create new synapses. Thosetaking part in the study had very early onset Alzheimer's, averaging about 25on a dementia scale from 1 to 30, with 30 being normal.
An additional study in prodromal patients—those who do nothave Alzheimer's but are starting to exhibit memory loss—is currently inprogress. Wurtman notes that there is a great deal of interest in looking atthe applications of Souvenaid in other conditions as well, such as Parkinson'sdisease and stroke.
 Nutricia, the specialized healthcare division of Danone(Dannon in the United States), sponsored both trials. While MIT has patentedthe nutrient mixture used in the study, Nutricia holds the exclusive licensefor the patent. Nutricia is currently testing and marketing Souvenaid, notedthat plans for commercial release of the mixture are not finalized, but it isexpected to be available in Europe first.

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