By Deborah Brauser
March 20, 2012 (Washington, DC) — AC-1202 (Axona, Accera Inc) may help improve practical cognitive tasks in patients with Alzheimer’s disease (AD), new research suggests.
In an analysis from a randomized controlled trial of elderly patients with mild to moderate AD, those who received AC-1202 for 90 days showed significantly higher performance improvement scores on constructional praxis/drawing tasks than the patients who received placebo.
In addition, the improvements persisted for 2 weeks after last administration.
“This suggests real-world benefit,” principal investigator David W. Crumpacker, MD, adult and geriatric psychiatrist in private practice in Plano, Texas, and former assistant chief of psychiatry at Baylor Medical Center in Dallas, told Medscape Medical News.
“And I would say the take-away for clinicians is that there are alternative treatments for Alzheimer’s disease based on metabolic strategies.”
Dr. Crumpacker presented the study results here at the American Association for Geriatric Psychiatry (AAGP) 2012 Annual Meeting.
Regional decline in cerebral metabolic rate of glucose metabolism (CMRglc) is a major feature of AD. However, “the systemic induction of ketosis has been shown to alleviate conditions of low CMRglc in a variety of neurological conditions, including AD,” write the investigators.
AC-1202 is a triglyceride composed of glycerine and caprylic acid. Its chemical name is 1,2,3-propanetriol trioctanoate.
As reported by Medscape Medical News, the US Food and Drug Administration (FDA) approved Axona in 2009 on the basis of initial findings from this study, which the investigators first presented at the 2007 Alzheimer’s Association International Conference on Prevention of Dementia.
The product, which is consumed as a beverage, is mixed in water and produces mild ketosis.
A total of 152 outpatients classified as having mild to moderate AD were randomly assigned to receive daily for 90 days either AC-1202 or placebo. The AD Assessment Scale–Cognition Subscale (ADAS-cog) was administered to all participants at baseline, at days 45 and 90, and after a 2-week wash-out period (day 104).
In the earlier analysis, the investigators found that the patients taking Axona, which was then called Ketasyn, had significant overall improvements on the ADAS-cog than those receiving placebo at days 45 and 90.
Potential Disease Modifier?
For this analysis, the researchers sought to assess improvements in constructional praxis (measured by a patient’s ability to copy 4 geometric forms in 2 attempts) in the subgroup of 53 participants who were apolipoprotein E4–negative [APOE4(-)]. Of these patients, 29 received AC-1202 and 24 received placebo.
“Constructional praxis is a broad concept which has been applied to a number of activities with the common characteristic that they require an individual to assemble, join, or articulate parts to form a single unitary structure,” explain the investigators.
“It’s the ability to draw, organize, and arrange things. People who can better do this are often better at recognizing things, participate more in conversations, and just do better executively,” added Dr. Crumpacker. “We wanted to focus on this, as opposed to word recall, because it shows a real practical application.”
Results showed that the APOE4(-) patients receiving AC-1202 had significantly better constructional praxis scores than the patients receiving placebo at days 45 (P = .015), 90 (P = .015), and 104 (P = .037).
“At each time point, the change from baseline for subjects receiving the medical food was -0.26 points and that for placebo was +0.33 points,” write the investigators.
Dr. Crumpacker reported that they hope to next examine whether AC-1202 is a possible disease modifier.
“Right now, we know that it can help these patients. But we aren’t sure just how long that lasts. Is it just while someone is taking the compound? Or can it be disease modifying if people stay on it? That’s the next step,” he said.
“I think this is intriguing and promising, but I’d like to see more. It would be nice to have a non-pharmaceutical-supported trial to look at this,” incoming AAGP president Paul Kirwin, MD, told Medscape Medical News.
Dr. Kirwin, who was not involved with this study, is also associate professor of psychiatry at the Yale School of Medicine in New Haven, Connecticut, and program director of Yale’s Geriatric Psychiatry Fellowship.
“I have concerns about what the long-term effects are of being on something that gives you mild ketosis. And as [the investigators] point out, there are concerns over whether or not someone can or would adhere to this diet,” he said.
“Also, we’d like to see what’s going on past 90 days. What’s going on at 6 months or a year? It would be interesting to see if there’s any lasting effect.”
Babak Azar, MD, geriatric psychiatrist at Southern New Hampshire Medical Center in Nashua, agreed with Dr. Kirwin’s assessment that more research is needed.
“A better score on a test doesn’t necessarily mean that a person can better do daily activities of life independently,” said Dr. Azar.
“Still, this was interesting and presents a new way of looking at a problem. But, as mentioned, it needs more research,” he said.
Dr. Kirwin noted that critical considerations include whether “something like this can delay functional decline” and if it can delay nursing home placement.
“There’s study after study that people who stay in their own home longer do better and have a much better quality of life. So something that can delay placement would be a big thing.”
Added Dr. Azar, “Even if you delay placement by 6 months, that would be a huge difference in a person’s life and in expense to the family.”
This study was supported by Accera, Inc. Dr. Crumpacker, Dr. Kirwin, and Dr. Azar have disclosed no relevant financial relationships.
American Association for Geriatric Psychiatry (AAGP) 2012 Annual Meeting. Abstract NR-11. Presented March 18, 2012.