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March 17, 2014
Study Points to Possible Blood Test For Memory Decline, Alzheimer’s
A new study identified a set of 10 compounds in the blood that might be used to identify older adults at risk for developing memory deficits or Alzheimer’s disease. More research is needed to confirm the findings, but the study suggests one possible approach for the early identification and treatment of cognitive decline.
Alzheimer’s disease is a progressive brain disorder that affects older adults. It gradually destroys their ability to think and remember. Estimates vary, but Alzheimer’s disease may affect as many as 5 million people over age 65 in the U.S. That number is expected to more than triple by 2050.
Despite extensive research, there are no effective therapies for preventing Alzheimer’s disease or slowing its progression. Many experts believe that successful treatment will depend on early intervention before symptoms appear. However, there’s no sure way to identify pre-symptomatic Alzheimer’s disease. Brain scans and spinal fluid tests are now being evaluated to identify certain at-risk individuals. Scientists have been intensely searching for simpler ways to predict memory decline and Alzheimer’s disease well before signs of memory loss appear.
Dr. Howard Federoff of Georgetown University Medical Center and his colleagues decided to search for biomarkers of early-stage Alzheimer’s disease in circulating blood. They enrolled 525 healthy adults, ages 70 and older, in a 5-year observational study. The research was funded in part by NIH’s National Institute on Aging (NIA). Results appeared online on March 9, 2014, in Nature Medicine.
Cognitive tests at enrollment showed that 46 participants had previously undiagnosed mild Alzheimer’s disease or mild cognitive impairment that mostly affected memory. This type of memory loss is sometimes an early sign of Alzheimer’s disease. Over the course of the study, 28 people with normal memory eventually developed either mild Alzheimer’s disease or impaired memory. The researchers classified this group as “converters.”
In the study’s third year, the scientists used advanced technologies to analyze the blood of 53 participants (including 18 converters) who had either impaired memory or Alzheimer’s disease. The researchers also studied 53 cognitively normal age- and sex-matched participants for comparison. In an approach known as metabolomics, the scientists used mass spectrometry to sort through hundreds of blood-based chemicals, called metabolites, produced during the body’s everyday activities.
A series of analyses pinpointed 10 lipids, or fats, that differed between those who were cognitively impaired, healthy people who later “converted,” and participants who remained healthy. These lipid metabolites might represent the weakening of nerve cell membranes in the early stages of Alzheimer’s disease.
To validate their findings, the scientists tested the 10-lipid panel in a blinded analysis. The team evaluated blood from 40 separate participants, including 10 converters. The test could distinguish with 90% accuracy between cognitively normal participants who remained healthy and those who became impaired within 2 to 3 years.
“The preclinical state of the disease offers a window of opportunity for timely disease-modifying intervention,” Federoff says. “Biomarkers such as ours that define this asymptomatic period are critical for successful development and application of these therapeutics.” The researchers note that the biomarker panel would require further validation in larger, diverse populations before it could be used clinically.
—by Vicki Contie
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References: Plasma phospholipids identify antecedent memory impairment in older adults. Mapstone M, Cheema AK, Fiandaca MS, Zhong X, Mhyre TR, Macarthur LH, Hall WJ, Fisher SG, Peterson DR, Haley JM, Nazar MD, Rich SA, Berlau DJ, Peltz CB, Tan MT, Kawas CH, Federoff HJ. Nat Med. 2014 Mar 9. doi: 10.1038/nm.3466. [Epub ahead of print]. PMID: 24608097.
Funding: NIH’s National Institute on Aging (NIA) and U.S. Department of Defense.