Previous studies had found that the experimental drug was generally well tolerated and resulted in a dose-dependent reduction of CSF beta-amyloid in healthy participants.
Dr. Forman’s research group conducted a randomized, double-blind, placebo-controlled Phase Ib trial of MK-8931 in persons with mild to moderate Alzheimer’s disease. The drug inhibits BACE1, one of two enzymes that produce beta-amyloid by breaking down amyloid precursor protein.
Participants received 12, 40, or 60 mg of MK-8931 or placebo (n = 8 per dose; n = 6 for placebo) daily for seven days. The investigators measured CSF beta-amyloid levels for 36 hours following the final dose using samples collected from lumbar catheterization.
In subjects who received placebo, mean CSF concentrations increased relative to baseline. In participants who received MK-8931, however, “multiple doses of 12 to 60 mg resulted in a dose-dependent reduction in CSF beta-amyloid, similar to that observed in healthy volunteers, and have enabled robust dose-response modeling,” stated Dr. Forman.
“Dose-response profiles predict that 12- and 40-mg MK-8931 will inhibit beta-amyloid production by greater than 50% and greater than 75%, respectively, in the majority of Alzheimer’s disease patients,” Dr. Forman concluded.
Population Screening for Dementia May Not Lead to Better Clinical Outcomes
Population screening for dementia may not necessarily improve patient outcomes, researchers reported.
“The pressure for faster diagnosis and for population screening is increasing despite the lack of effective early treatment,” said Carol Brayne, MD, PhD, Professor at the Cambridge Institute of Public Health in the United Kingdom. “Yet we found no evidence that, if rolled out, population screening would lead to better clinical or psychosocial outcomes, no evidence furthering our understanding of the risks it entails, and no indication of its added value compared to current practice.”
The researchers reviewed studies that involve population screening and the clinical, psychosocial, and economic outcomes related to dementia. Eligible studies included those that examined population screening on its own or as a component of dementia intervention. The studies also compared outcomes with a routine pattern of care in the general population, among patients in general medical practice, and among patients in community care. Relevant papers through May 2012 were identified by database searches.
“Not one of these papers revealed evidence of benefit,” said Dr. Brayne. However, she added, “Absence of evidence is not evidence of absence.”
The investigators did not identify any studies that examined potential negative consequences caused by the screening results, such as the risk of depression, anxiety, or stigma. Regarding economic outcomes, three primary studies reported on the direct cost per patient diagnosed, two related studies compared a population screening scenario with other models of dementia care, and one study analyzed screening in older drivers.
“This suggests that substantial resources are required to screen for dementia,” noted Dr. Brayne. Cost factors include the age of the screened population, the properties of the screening instrument, and the extent to which general practitioners are involved in follow-up assessments, she added.
“Policymakers should be cautious about the adoption of population screening for dementia without any evidence of benefits or risks,” concluded Dr. Brayne.
“There appears to be no persuasive evidence to support the role of early detection by screening a general population with a single, brief interview,” commented moderator Ralph Nixon, MD, PhD, Director of Research at the Center for Dementia Research, New York University Langone Medical Center, in New York City. “There is no substitute for a rigorous, multidisciplinary approach to evaluation of memory impairment by a professional experienced with the symptomatology and evaluation of dementia.”
—Colby Stong
Editor