Researchers from six universities have developed an experimental blood test that may be able to be used to predict whether someone will develop dementia or Alzheimer disease (AD). The results of a study conducted by the researchers were published online on March 9 in a research letter in Nature Medicine.
Alzheimer disease is an irreversible form of dementia characterized by memory loss, a progressive decline in intellectual ability, deteriorating language and speech skills, and personality and behavioral changes. More than 5 million Americans are currently living with this disease and it is the 6th leading cause of death in the U.S., according to the Alzheimer's Association. The risk of having AD increases greatly with age.
Alzheimer disease has three stages: preclinical AD characterized by measurable changes in biomarkers but no outward symptoms; mild cognitive impairment (MCI) defined as mild changes in memory and thinking abilities that do not compromise day to day activities; and dementia due to AD with memory, thinking, and behavioral symptoms that impair a person's ability to function in daily life.
There is no known prevention or cure for Alzheimer disease and currently there are no laboratory tests available that will positively diagnose AD during life. The only way to definitively diagnose AD is to microscopically examine a section of the person's brain tissue at autopsy to look for senile plaques and neurofibrillary tangles characteristic of AD. Laboratory tests for the current biomarkers tau protein and amyloid beta 42 can suggest the diagnosis but can only be performed on cerebrospinal fluid (CSF), which is hard to obtain compared to a blood sample. A reliable test for the condition could help development of new treatments and possible preventive measures against the disease.
The experimental test measures the levels of 10 substances called phospholipids in blood. The researchers say that the breakdown of nerve cell membranes results in these phospholipids circulating in the blood. Two of the 10 metabolites have strong links to the disease process in AD. The test can detect alterations in the level of these substances that may be indicators (biomarkers) of the changes that occur during the development of Alzheimer disease, but before symptoms appear.
The scientists conducted their research among 525 healthy adults age 70 and older who were given the blood test every year for 5 years to measure the biomarkers. During those years, 74 were found to have or developed mild cognitive impairment or Alzheimer disease. Their blood test results were compared with the tests of the study participants who did not develop cognitive impairment. The researchers found that the dementia group had consistently lower levels of the lipid biomarkers than the healthy group and that the test had 90% accuracy in identifying persons with evidence of dementia. The test was abnormal even before the dementia began.
"Our novel blood test offers the potential to identify people at risk for progressive cognitive decline and can change how patients, their families and treating physicians plan for and manage the disorder," said the study's corresponding author, Dr. Howard J. Federoff, executive vice president of health sciences at Georgetown University Medical Center, in a press release.
Dr. Federoff said that the researchers plan to "design a clinical trial where we’ll use this panel to identify people at high risk for Alzheimer's to test a therapeutic agent that might delay or prevent the emergence of the disease."
But other scientists caution that the results must be replicated in other laboratories and that the researchers may be overly optimistic about the clinical benefit of the test, at least so far. In an article in MedPage Today, deputy managing editor John Gever wrote, "If the study cohort's 5% rate of conversion from normal cognition to mild impairment or Alzheimer's disease is representative of a real-world screening population, then the test would have a positive predictive value of just 35%. That is, nearly two-thirds of positive screening results would be false…In general, a positive predictive value of 90% is considered the minimum for any kind of screening test in normal-risk individuals."
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Mapstone M, et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nature Medicine. Published online 9 March 2014; doi:10.1038/nm.3466.
Mar 9, 2014. Gever, John. Researchers Claim Blood Test Predicts Alzheimer's. Medpage Today Neurology. Available online through http://www.medpagetoday.com. Accessed March 16, 2014.
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March 10, 2014. Young, Kelly. Blood Test Shows Early Promise in Identifying People at Risk for Alzheimer Disease. JournalWatch. Available online at http://www.jwatch.org/fw108575/2014/03/10/blood-test-shows-early-promise-identifying-people-risk?query=pfw through http://www.jwatch.org. Accessed March 16, 2014.
March 10, 2014. Bahrampour, Tara. Blood test may predict onset of Alzheimer's and related disease, new study finds. Washington Post. Available online through http://www.washingtonpost.com. Accessed March 16, 2014.
March 9, 2014. New Blood Test Can Predict Alzheimer's, Mild Dementia. Georgetown University. Available online at http://www.georgetown.edu/research/news/howard-federoff-alzheimers-blood-test.html through http://www.georgetown.edu. Accessed March 18, 2014.
(©2014) Alzheimer's Disease. Alzheimer's Association. Available online at http://www.alz.org/alzheimers_disease_1973.asp through http://www.alz.org. Accessed March 18, 2014.