Findings suggest the test can reduce the need
for PET imaging in some patients with mild cognitive decline to
enable therapeutic focus on non-Alzheimer's disease causes,
broadening access to quality evaluation and lowering healthcare
costs
SECAUCUS, N.J., March 26,
2024 /PRNewswire/ -- A blood test that analyzes
levels of amyloid proteins by highly sensitive mass spectrometry
could help physicians establish that Alzheimer's disease (AD) is
likely not the cause of patients' mild cognitive impairment, finds
a new study published in Frontiers in Neurology by
researchers from Quest Diagnostics (NYSE: DGX), the University of Florida and Mount Sinai Medical
Center in Miami Beach.
According to the analysis, up to 99% of patients with a negative
result for amyloid proteins in the brain using an imaging procedure
called positron emission tomography (PET) would likely be negative
using a blood test that evaluates a ratio of amyloid beta 42 and 40
proteins (Aβ42/40), which are found in the brain and also circulate
in the blood stream. With this level of prediction, the
investigators determined the test could help reduce PET brain scan
evaluations by about 40%, with potentially substantial savings in
healthcare costs for these patients.
While amyloid PET imaging is an established method for aiding
diagnosis of AD, it is significantly more expensive, invasive and
specialist-dependent than blood tests.
"The findings of this analysis in a large cohort have
significant implications for AD care management, because they
potentially mean many patients could benefit from this type of
blood-based assay that has advantages relative to current
approaches," said co-author David E.
Vaillancourt, PhD, Orchid Professor and Chair Applied
Physiology and Kinesiology, College of Health and Human
Performance, Fixel Institute of Neurological Disorders and
Director, 1Florida ADRC Biomarker Core.
The study, Clinical utility of plasma Aβ42/40 ratio by
LC-MS/MS in Alzheimer's disease assessment, is believed to be
one of the largest published studies to evaluate amyloid blood
testing for AD assessment. The investigators analyzed 6,192
deidentified laboratory test results from patients whose physicians
submitted specimens for testing by Quest's Aβ42/40 ratio test
(brand name Quest AD-Detect® Beta-amyloid ratio testAΒ42/40).
Clinical performance of the Quest test was established using 250
specimens from participants with amyloid PET imaging and
demographic data from the 1Florida Alzheimer's Disease Research
Center. Quest introduced the AD-Detect™ test to physicians in early
2022.
The investigators also evaluated the performance of the blood
test by different interpretative ranges based on different cutoffs,
or amyloid levels in the blood. Proposed guidelines from the
National Institutes of Aging recommend blood biomarker testing
account for different ranges by cutoff levels, including an
intermediate range, to support clinical decision making.
Key findings:
High NPV across populations: The test's negative
predictive value (NPV) was 99% (at the highest cutoff of 0.170) in
a population with moderate prevalence of AD (40%) as determined by
PET-positivity. NPV represents the likelihood a disease is not
present in a given population. The investigators then applied the
NPV of 99% to the population of 6,192 deidentified specimens tested
by Quest for Aβ42/40. They determined that 40% of that population
could reliably forgo additional evaluation by PET, which costs
about $5,000 per scan.
High sensitivity for AD PET-positivity at lower cut off:
The test was 91% sensitive for detecting AD, as determined by PET
scan at a cutoff of 0.160 in a population with moderate prevalence
of PET-positivity of 40%.
In the same population and cutoff, the specificity was 76%. The
same investigative team recently published results of a study in
Alzheimer's & Dementia that showed the "novel and
important" finding that abnormal Aβ42/40 blood testing
"associates with quantifiable changes in the tissue and
extracellular microstructural environments" of the brain, even in
PET-negative patients.
"These findings show Aβ42/40 testing is very helpful in
identifying amyloid pathology in populations with a high prevalence
of AD, particularly older individuals," said study co-author
Michael Racke, MD, Medical Director
of Neurology at Quest Diagnostics. "We believe the comparatively
low specificity reflects the limits of PET scans to identify the
earliest stages of AD pathology and that many of these patients
will progress to be PET-positive as the disease worsens."
APOE4 did not influence accuracy, possibly due to population
diversity: APOE4 alleles did not substantially improve accuracy
of the Aβ42/40 test, in contrast to other research. Investigators
theorize this was due to a higher than typical percentage of
patients of Hispanic heritage in the study population. APOE4 is a
genetic trait that raises risk of AD and is more likely to
correlate with PET-positive results in patients who are White than
Hispanic.
"Our findings are a cautionary note that algorithms
incorporating Aβ42/40 and APOE4 allele status may not be generally
applicable for all races and ethnicities," wrote the authors.
Nearly 7 million Americans have Alzheimer's, the most prevalent
dementia, a number projected to reach 14 million by 2060. New blood
tests offer the potential for primary care physicians as well as
specialists to identify people at risk for Alzheimer's disease even
before symptoms manifest.
To access the complete study, including methodology, strengths
and limitations: Frontiers | Clinical utility of plasma Aβ42/40
ratio by LC-MS/MS in Alzheimer's disease assessment
(frontiersin.org)
About Quest Diagnostics
Quest Diagnostics works across
the healthcare ecosystem to create a healthier world, one life at a
time. We provide diagnostic insights from the results of our
laboratory testing to empower people, physicians and organizations
to take action to improve health outcomes. Derived from one of the
world's largest databases of de-identifiable clinical lab results,
Quest's diagnostic insights reveal new avenues to identify and
treat disease, inspire healthy behaviors and improve healthcare
management. Quest Diagnostics annually serves one in three adult
Americans and half the physicians and hospitals in the United States, and our nearly 50,000
employees understand that, in the right hands and with the right
context, our diagnostic insights can inspire actions that transform
lives and create a healthier world. www.QuestDiagnostics.com.
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