Medical foods and supplements designed to support neural health and function may soon expand treatment options for common forms of dementia based on the results of two studies.

One study found that a cocktail of compounds designed to support synapse formation and function improved memory in patients with mild Alzheimer’s disease. The other found that oral citicoline, a substrate for acetylcholine synthesis that inhibits neurodegeneration, yielded better memory than no treatment in patients with mild cognitive impairment (MCI) due to vascular causes.

The findings may signal the start of an era in which Alzheimer’s disease and other dementias are managed with a multimodality approach involving a variety of pharmacologic and nonpharmacologic strategies, according to Maria Carrillo, Ph.D., senior director of medical and scientific relations for the Alzheimer’s Association. “We need to continue to be open to different therapeutic avenues and approaches,” she commented while moderating a press briefing at the Alzheimer’s Association International Conference 2012, where the data were first presented.

Souvenaid for Mild Alzheimer’s Disease

Susan London/IMNG Medical Media

Dr. Philip Scheltens

In the first trial, known as Souvenir II, researchers led by Dr. Philip Scheltens of the VU University Medical Center in Amsterdam studied 259 patients from multiple centers in Europe who had mild Alzheimer’s disease, with a Mini-Mental State Examination (MMSE) score of 25 or greater.

Patients were randomized evenly to receive Souvenaid (125 mL orally once a day) or a control drink for the first 24 weeks. Souvenaid contains a special formulation of omega-3 and -6 fatty acids, choline, phospholipids, B vitamins, and antioxidants designed to promote the formation and function of synapses, he explained.

“Synapse dysfunction is … critical to causing symptoms in Alzheimer’s disease. It’s not the amyloid load that causes memory problems – it’s the loss of synapses and the loss of neurons that do so,” he noted. In a subsequent 24-week extension period, all patients received Souvenaid.

Rates of serious adverse events did not differ between groups, and there were no new safety signals during the extension period, Dr. Scheltens reported.

Compliance was uniformly high in both groups during both periods, ranging from 93% to 97%. “People really liked [Souvenaid] and stayed on the product the whole time,” he said. “There are two flavors: strawberry and vanilla. It’s like a drinkable yogurt. … It tastes very, very good, and that’s why the compliance was so high. Although the amount of fish oil in it is equivalent to three or four herrings, you would be surprised that it doesn’t smell at all like fish or taste like fish.”

At 24 weeks, patients in the Souvenaid group had a significantly greater improvement from baseline in z scores for the Neuropsychological Test Battery memory domain (P = .023) and marginally better total composite scores (P = .053), as recently published (J. Alzheimers Dis. 2012;31:225-36).

In additional results, there was a significant improvement between 24 and 48 weeks in the z score for the memory domain of the Neuropsychological Test Battery among both patients who started and continued on Souvenaid (P = .025) and patients who started on the control drink and switched to Souvenaid (P = .009).

“The memory actually even improved further; there was no ceiling effect on memory,” Dr. Scheltens commented. “So the mild patients could even improve further.”

The effect size in the study was 0.21, “exactly on the order of the cholinesterase inhibitors,” he pointed out. “But the risk-benefit ratio is much better, because there are no side effects and people can take it as long as they want.”

“We think this may offer a new approach, a dietary management approach, if you like, in people with very early Alzheimer’s disease,” Dr. Scheltens concluded. “We are continuing the [research] program because we think it is worthwhile to pursue this in a rigorous, scientifically oriented way. The targeted patient population will be the mild to very mild Alzheimer’s disease patients.”

He said it’s unlikely that combining individual dietary supplements could achieve the benefit seen with Souvenaid. Studies of various individual components have shown “they basically don’t work. Only the particular combination of all these nutrients is needed and is necessary to build up the membrane of the synapse. So it’s just not something you can do at home – throw a little bit of this, a little bit of that in a tube. It is the specific combination and the ratio between the [components of the] combination that actually works.”

Assuming Souvenaid makes it to the market, it will be classified as a medical food. “That means it has to be prescribed by a doctor and it needs to be delivered by a pharmacist. It is not over the counter,” Dr. Scheltens noted. He expects that the product will first be launched in Europe, as the manufacturer is located there.

Citicoline for Vascular MCI

Susan London/IMNG Medical Media

Dr. Pietro Gareri

In the second trial, known as IDEALE, Dr. Pietro Gareri, a geriatrician with the Ambulatory Center for Dementia in Catanzaro, Italy, and his colleagues enrolled 349 patients in Italy at least 65 years of age who had evidence of vascular lesions on neuroradiologic imaging, and either an MMSE score of at least 21 or subjective memory complaints. (Those with probable Alzheimer’s disease were excluded.)

The patients were assigned in a 3:1 ratio to open-label treatment with citicoline (500 mg twice a day) or a control condition (no treatment).

“Citicoline has a number of different properties,” Dr. Gareri explained. “For example, it inhibits apoptosis associated with cerebral ischemia. And it’s able to inhibit several models of neurodegeneration. It’s able to potentiate neuroplasticity. And it is a natural precursor of phospholipid synthesis.”

Trial results showed a nonsignificant increase in MMSE scores over 6 months in the citicoline group (from 22.4 to 22.9), compared with a decrease in scores in the control group (from 21.5 to 19.6). Scores differed significantly between groups at 3 months and at 6 months.

Both groups had improvements in functional dependence, as assessed from activities of daily living and instrumental activities of daily living, with no significant between-group difference.

There was a trend toward better Geriatric Depression Scale scores with citicoline (P = .06). “This was not a surprise, because citicoline increases noradrenaline and dopamine levels in the central nervous system,” Dr. Gareri commented. None of the patients experienced adverse events.

“Definitively, this study shows that citicoline is effective and safe. Therefore it can be recommended in vascular mild cognitive impairment,” he concluded.

Neither Dr. Scheltens nor Dr. Gareri disclosed any relevant conflicts of interest.