Diagnostic Tests

What Physicians Need to Know

PrecivityAD for Diagnosis of Alzheimer Disease

 

Am Fam Physician. 2022 Jan ;105(1):79-81.

PrecivityAD is a blood test marketed to aid in the diagnosis of Alzheimer disease in patients 60 years or older with cognitive impairment. It is currently available in 47 states, the District of Columbia, and Puerto Rico. PrecivityAD is not approved by the U.S. Food and Drug Administration (FDA) but received breakthrough device designation from the FDA in 2019.

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TestIndicationPopulationCost*

PrecivityAD

Evaluation for Alzheimer disease

Patients 60 years and older with mild cognitive impairment

$1,250


*—Payment rate according to Scientific American.10

TestIndicationPopulationCost*

PrecivityAD

Evaluation for Alzheimer disease

Patients 60 years and older with mild cognitive impairment

$1,250


*—Payment rate according to Scientific American.10

Using mass spectrometry, the PrecivityAD test quantifies the concentration ratio of two amyloid-beta (Abeta) peptides, Abeta 42 and 20, and detects apolipoprotein E (apoE) genotype. These markers help determine the diagnostic probability of Alzheimer disease.1,2 These values, along with the patient's age, are used in a proprietary algorithm to provide an Amyloid Probability Score (APS). The APS is stratified as low (0 to 35) or high (58 to 100); a score of 36 to 57 is considered intermediate and requires further evaluation. A high APS indicates a higher likelihood that the patient will have amyloid plaques on amyloid positron emission tomography (PET).3

Accuracy

The APS produced by PrecivityAD testing predicts the likelihood of an amyloid-positive PET result, with its accuracy having been evaluated in low-quality studies. Amyloid PET is highly sensitive (91%) and specific (92%) for distinguishing autopsy-confirmed Alzheimer disease from non–Alzheimer disease dementia.4 In those with mild cognitive impairment, amyloid PET imaging may also help with prognostication because positive imaging findings suggest a higher chance of conversion to Alzheimer disease.5

Table 1 shows the results of two studies evaluating the diagnostic accuracy of the APS and its components.1,6,7 In a prospective cohort study, 210 samples from 158 patients with normal cognition who underwent amyloid PET within the previous 18 months were analyzed for the Abeta42/Abeta20 ratio and apoE genotype. Using a ratio cutoff of less than 0.1218 to define positivity, a positive result was predictive of positive amyloid PET results. Combining the plasma Abeta42/Abeta40 ratio, patient age, and apoE genotype improved concordance with amyloid PET findings.1 A subgroup analysis of 74 patients with negative amyloid PET findings initially showed that those with a positive plasma Abeta42/Abeta20 ratio had a 15-fold higher risk of developing brain amyloidosis seen on amyloid PET compared with those who had a negative ratio (mean duration after baseline serologic testing and last amyloid PET scan was 3.9 ± 1.4 years, with a range of 1.9 years to 9.0 years).1

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TABLE 1.

Prediction of Positive Amyloid PET Findings

Patient groupTestAUROC*Sensitivity, specificityLR+, LR−Posttest probability of brain amyloidosis†

PositiveNegative

Asymptomatic, 46 to 86 years of age

Abeta42/Abeta40 ratio‡

0.88

88%, 76%

3.67, 0.16

79%

14%

Age plus Abeta42/Abeta40 ratio‡ plus apolipoprotein E genotype

0.94

Data not available

Cognitive impairment, 60 to 91 years of age

Abeta42/Abeta40 ratio‡

0.84

84%, 73%

3.11, 0.22

76%

18%

Amyloid probability score

0.88

92%, 77%

4.00, 0.10

80%

9%


Abeta = amyloid beta; AUROC = area under the receiver operating characteristic curve; LR– = negative likelihood ratio; LR+ = positive likelihood ratio; PET = positron emission tomography.

*—In general, an AUROC above 0.85 means high agreement or accuracy, 0.75 to 0.85 means moderate accuracy, and less than 0.75 means low accuracy.

†—Assuming a baseline prevalence of 50%.

‡—Abeta42/Abeta40 ratio positivity defined by a cutoff of less than 0.1218.

Information from references 1, 6, and 7.

TABLE 1.

Prediction of Positive Amyloid PET Findings

Patient groupTestAUROC*Sensitivity, specificityLR+, LR−Posttest probability of brain amyloidosis†

PositiveNegative

Asymptomatic, 46 to 86 years of age

Abeta42/Abeta40 ratio‡

0.88

88%, 76%

3.67, 0.16

79%

14%

Age plus Abeta42/Abeta40 ratio‡ plus apolipoprotein E genotype

0.94

Data not available

Cognitive impairment, 60 to 91 years of age

Abeta42/Abeta40 ratio‡

0.84

84%, 73%

3.11, 0.22

76%

18%

Amyloid probability score

0.88

92%, 77%

4.00, 0.10

80%

9%


Abeta = amyloid beta; AUROC = area under the receiver operating characteristic curve; LR– = negative likelihood ratio; LR+ = positive likelihood ratio; PET = positron emission tomography.

*—In general, an AUROC above 0.85 means high agreement or accuracy, 0.75 to 0.85 means moderate accuracy, and less than 0.75 means low accuracy.

†—Assuming a baseline prevalence of 50%.

‡—Abeta42/Abeta40 ratio

Address correspondence to Jacob Anderson, DO, at Jacob.Anderson@bannerhealth.com. Reprints are not available from the authors.

Author disclosure: No relevant financial relationships.

References

show all references

1. Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93(17):e1647–e1659....

2. Hauser PS, Ryan RO. Impact of apolipoprotein E on Alzheimer's disease. Curr Alzheimer Res. 2013;10(8):809–817.

3. Ballard C, Gauthier S, Corbett A, et al. Alzheimer's disease. Lancet. 2011;377(9770):1019–1031.

4. Fink HA, Hemmy LS, Linskens EJ, et al. Diagnosis and treatment of clinical Alzheimer's-type dementia: a systematic review. Comparative Effectiveness Review, no. 223. AHRQ publication no. 20-EHC003. Agency for Healthcare Research and Quality. April 2020.

5. Suppiah S, Didier M-A, Vinjamuri S. The who, when, why, and how of PET amyloid imaging in management of Alzheimer's disease—review of literature and interesting images. Diagnostics (Basel). 2019;9(2):65.

6. Tape TG. Interpreting diagnostic tests. The area under an ROC curve. The University of Nebraska. Accessed March 25, 2021. http://gim.unmc.edu/dxtests/roc3.htm

7. Precivity AD. Physicians: About PrecivityAD. Accessed March 10, 2021. http://precivityad.com/physicians

8. Precivity AD. Physicians: FAQs. Accessed November 23, 2021. https://precivityad.com/physician-faqs

9. Sperling RA, Donohue MC, Raman R, et al.; A4 Study Team. The anti-amyloid treatment in asymptomatic Alzheimer's disease (A4) study: report of screening data results. Alzheimers Dement. 2018;75(14 pt 3):P215–P216.

10. Landhuis E. Detecting Alzheimer's gets easier with a simple blood test. Scientific American. February 4, 2021. Accessed March 10, 2021. https://www.scientificamerican.com/article/detecting-alzheimers-gets-easier-with-a-simple-blood-test

11. George J. Alzheimer's diagnoses change with amyloid PET scans. MedPage Today. April 2, 2019. Accessed March 10, 2021. https://www.medpagetoday.com/neurology/alzheimersdisease/78974

12. PET (FDG) for Dementia and Neurocognitive Diseases. National Coverage Determination. Centers for Medicare & Medicaid Services. April 2005. Accessed November 23, 2021. https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=288&ncdver=2&bc=AAAAIAAAAQAA&=

This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

A collection of Diagnostic Tests published in AFP is available at https://www.aafp.org/afp/diagnostic.

 

 

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