AC-1202 Improves Cognition in APOE*E4-Negative Patients with AD. A medium chain triglyceride that converts to ketone bodies and counteracts reduced glucose metabolism improves cognitive scores in patients with mild to moderate Alzheimer disease (AD) who do not have the e4 allele of the apolipoprotein E (APOE*E4) gene.
The association between treatment response and the APOE*E4 genotype was initially observed in the first installment of a phase 2 clinical trial, the results of which were published in March 2004 (Reger MA, Henderson ST, Hale C, et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging. 2004;25:311-314). In that study, ketone body levels rose significantly 90 to 120 minutes after treatment with AC-1202 in patients with AD or mild cognitive impairment who were APOE*E4-negative, but remained constant in those patients who were APOE*E4-positive. Higher ketone values and APOE*E4-negative status were associated with improvement on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog).
In the current installment of the trial, reported during a Late-Breaking Science session by Lauren C. Costantini, PhD, vice president of clinical development for the agent's manufacturer, Accera, 152 patients with probable AD of mild to moderate severity were randomly selected to receive 20 g of either AC-1202 or a placebo once daily for 90 days. Change in mean ADAS-cog score from baseline was not statistically significant for the 38 patients who were APOE*E4-positive, but changed significantly (mean change, 3.36 points) in the 29 patients who were APOE*E4-negative.
Response to Famous Faces Linked to Gray Matter Atrophy. A patient's inability to recognize a famous person in a photograph may indicate that certain brain regions are affected by neurodegenerative disease, according to research from the University of California, San Francisco.
Voxel-based morphometry was used to correlate MRI-based gray matter volumes with performance on 3 face-association tests: choosing the famous face from a group of 4 similar photographs, naming the profession common to the famous persons shown in a set of photographs, and naming a single famous person based on a photograph. The study population included 48 patients with a range of neurodegenerative diseases and a control group of 9 clinically normal persons.
Familiarity judgment was positively correlated with gray matter volume in the right middle temporal gyrus; semantic association with the left fusiform and inferior temporal gyri; and naming with the left middle, inferior temporal, and fusiform gyri. All correlations were statistically significant.
Medication Affects Height, Weight in Tourette Syndrome. Marked differences in height and weight can be seen in children with Tourette syndrome depending on whether they are taking medication or are medication-naive, according to a team led by Debabrata Ghosh, MD, a pediatric neurologist at the Cleveland Clinic.
In a single-center review of about 2000 patients, the researchers identified 122 medication-naive patients (aged 12 ± 3.5 years). When parameters related to height, weight, and body mass index (BMI) in these patients were compared with the standard established by the CDC, it was revealed that the medication-naive young persons with Tourette syndrome were shorter and weighed less than the standard for their age but their BMIs were normal. Inhibition of prolactin associated with dopamine(Drug information on dopamine) excess in the hypothalamic-pituitary axis may play a role, according to Ghosh.
He noted that until recently, children with Tourette syndrome were thought to be larger—not smaller—that normal peers. The false observation was attributed to the fact that clinical practice and research primarily focused on patients with more severe disease who were receiving medication.
The respective citations for the meeting presentations that correspond with these news briefs are as follows:
- Costantini LC, Vogel JL, Barr LJ, Henderson ST. Clinical efficacy of AC-1202 (Ketasyn) in mild to moderate Alzheimer's disease. Presented at: 59th Annual Meeting of the American Academy of Neurology. Boston. April 28-May 5, 2007.
- Gorno-Tempini ML, Narvid J, Brambati S, et al. The neuroanatomy of famous face processing in neurodegenerative disease. Neurology. 2007;68(suppl 1):A98-A99.
- Ghosh D, Das D, Worley S, Erenberg G. Height and weight are decreased with normal BMI in children with Tourette syndrome—possible indicator for dopamine excess in the hypothalamico-pituitary axis. Neurology. 2007;69(suppl 1):A155.
