CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Biomarker testing for Alzheimer disease (CSF, blood, urine)

Defines coverage and medical necessity for cerebrospinal fluid, blood, and urinary biomarker testing for Alzheimer disease and mild cognitive impairment for BCBSRI Medicare Advantage and Commercial products.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyBiomarker testing for Alzheimer disease (CSF, blood, urine)

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateJan 1, 2024

Next Review DateN/A

Key ActionOnly the ordering physician may handle authorization and appeals; laboratories must not obtain prior authorization on behalf of the ordering physician.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Not coveredCoverage stance

4Named tests

52References

CLIALab certification

ListedNamed CPTs not covered

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Coverage Determinations

Coverage stance for CSF, blood, and urine biomarkers

Coverage determination for Medicare Advantage Plans and Commercial Products

Main coverage decision: Cerebrospinal fluid (CSF) biomarker testing (including but not limited to amyloid beta peptides, tau protein, or neural thread proteins) is not covered for Medicare Advantage Plans and is considered not medically necessary for Commercial Products.

Evidence is insufficient to determine effects on health outcomes for diagnosis, prognosis, or management decisions.

Adjunct to clinical diagnosis — CSF: Use of CSF biomarker testing as an adjunct to clinical diagnosis in individuals with mild cognitive impairment (MCI) is not covered for Medicare Advantage Plans and is not medically necessary for Commercial Products.

Relevant evidence includes systematic reviews and observational studies with uncertain generalizability; clinical utility for improving net health outcomes is not established.

Adjunct to clinical diagnosis — mild dementia due to AD: Use of CSF biomarker testing as an adjunct to clinical diagnosis in individuals with mild dementia due to Alzheimer disease is not covered for Medicare Advantage Plans and is not medically necessary for Commercial Products.

Evidence insufficient to demonstrate improved net health outcomes.

Evaluation for initiation/continuation of amyloid-targeting therapy: Use of CSF biomarker testing as part of an evaluation for initiation or continuation of amyloid beta–targeting therapy in individuals with MCI or mild dementia due to Alzheimer disease is not covered for Medicare Advantage Plans and is not medically necessary for Commercial Products.

Insufficient evidence that testing affects treatment decisions that improve health outcomes.

Blood and urine biomarkers: Measurement of blood and urinary biomarkers as an adjunct to clinical diagnosis in individuals with MCI or mild dementia due to Alzheimer disease is not covered for Medicare Advantage Plans and is not medically necessary for Commercial Products.

Systematic reviews and cohort studies for plasma biomarkers (eg, plasma p-tau) and urinary biomarkers show uncertain clinical validity and insufficient evidence of net health benefit.

Authorization process note: Only the ordering physician shall be involved in the authorization, appeal, or other administrative processes related to prior authorization/medical necessity; laboratories are not allowed to obtain authorization on behalf of the ordering physician.

Operational requirement; laboratories and their representatives must not participate in obtaining clinical authorization for the ordering provider.

For self-funded groups, coverage for certain genetic testing services and expanded biomarker testing may be limited by the employer contract. Providers and billing staff should refer to the member's Benefit Booklet and the related Genetic Testing Services or Proprietary Laboratory Analyses policies to determine whether a specific test is covered, not medically necessary, or excluded by contract.

Services that the policy identifies as not medically necessary or that are classified as non-covered benefits may be excluded from payment. Providers must verify member-specific benefits and eligibility prior to ordering; if a service is determined to be not medically necessary or a non-covered benefit, the provider may not bill the member unless the member has expressly agreed in writing in advance. This policy is informational and not a guarantee of payment; the member's subscriber agreement or employer agreement governs benefits.

Cerebrospinal fluid (CSF), urinary, and blood biomarker testing are considered adjuncts to clinical diagnosis in the policy context. The evidence is judged insufficient to demonstrate improved net health outcomes when these biomarker tests are used as adjuncts for individuals with mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease, or to guide initiation or continuation of amyloid-targeting therapy. Accordingly, CSF, urinary, and blood biomarker testing used in these adjunctive roles are not supported by this policy.

Covered Indications and Evidence Summary

None specified as covered — assays with FDA Breakthrough/marketing authorization

None of the following assays or platforms are designated as covered in this policy.

Assays with regulatory milestones: Some assays have received FDA Breakthrough Device designation or FDA marketing authorization (for example, the Lumipulse G ß-Amyloid Ratio CSF immunoassay and certain plasma assays such as Precivity), and some laboratories hold CLIA certification for specific plasma assays.

Despite regulatory designations and CLIA certification, the policy does not designate these tests as covered.

Regulatory status examples: Examples include: Lumipulse G ß-Amyloid Ratio immunoassay (FDA De Novo marketing authorization; intended for adults ≥55 years), Elecsys Amyloid Plasma Panel (FDA Breakthrough Device designation), and Precivity mass-spec plasma amyloid assay (CLIA certified; FDA breakthrough designation).

These assays are discussed for informational/regulatory context only; coverage is not established by this policy.

Diagnostic evaluation of AD and MCI using CSF and blood biomarkers — evidence and guidance

Diagnostic evaluation context and supporting evidence for CSF and blood biomarkers in AD and MCI.

Clinical application: CSF and blood biomarkers (eg, amyloid beta peptides, total tau, phosphorylated tau, Aβ42/40 ratio, plasma p-tau181/p-tau217) have been studied to support diagnosis and prognosis in individuals with Alzheimer disease (AD) or mild cognitive impairment (MCI).

Studies include systematic reviews, cohort studies, and validation research comparing biomarkers to neuropathology or amyloid PET.

Evidence limitations — CSF: Clinical validity studies of CSF biomarkers often derive from selected patient samples with defined optimal cutoffs lacking external validation; generalizability is uncertain and evidence is insufficient to conclude improved net health outcomes.

References include meta-analyses and consensus guidance on preanalytical standardization.

Evidence limitations — blood and urine: Blood biomarker studies (notably plasma p-tau) show promise for screening and diagnosis, but whether earlier diagnosis leads to improved health outcomes (eg, delayed onset, improved quality of life) is unknown; urinary biomarker evidence is limited with uncertain clinical validity.

Systematic reviews and recent validation studies are cited; clinical utility remains unproven.

Codes and Coding Notes

Named biomarker CPT/Unlisted codesCPT

0445U	Elecsys® PhosphoTau (181P) CSF (pTau181) and β-Amyloid (1-42) CSF II (Abeta 42) Ratio (Roche Diagnostics)
0361U	Neurofilament light chain, digital immunoassay, plasma, quantitative (Mayo Clinic)
0443U	Neurofilament light chain (NfL), ultra-sensitive immunoassay, serum or cerebrospinal fluid (Washington University)
0412U	Beta amyloid, Aβ42/40 ratio, immunoprecipitation with quantitation by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and qualitative ApoE isoform-specific proteotyping, plasma (PrecivityAD®)
81099	Unlisted Urinalysis Procedure
86849	Unlisted Immunology Procedure
83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified

ICD-10 Diagnosis Codes referencedICD-10

F03.90-F03.91	Unspecified dementia
G30.0-G30.9	Alzheimer disease
G31.1	Senile degeneration of brain
G31.84	Mild cognitive impairment, so stated
R41.81	Age-related cognitive decline

Age for Lumipulse intended use

Lumipulse intended age rangeAdults aged ≥ 55 years

Indication contextIntended for adult patients presenting with cognitive impairment who are being evaluated for Alzheimer disease and other causes of cognitive decline

Regulatory noteLumipulse G ß-Amyloid Ratio received marketing authorization via De Novo review and breakthrough device designation

Provider Responsibilities and Billing Impact

Prior Authorization

Prior authorization is not applicable for this policy.

Denial Risk

Benefit Verification and Billing Risk

Cerebrospinal fluid, urinary, and blood biomarker tests described in this policy are not covered for Medicare Advantage Plans and are considered not medically necessary for Commercial Products. Providers must verify member-specific benefits and eligibility prior to ordering. If services are determined to be not medically necessary or not a covered benefit, the provider may not charge the member unless the member was informed and provided written agreement in advance to pay at their own expense.

Affected tests: cerebrospinal fluid biomarkers (amyloid beta peptides, tau protein, neural thread proteins) and urinary/blood biomarkers used as adjuncts to diagnosis in MCI or mild dementia.
Providers must call the provider call center for member-specific benefits and eligibility verification.

Billing Rule

Authorization Process and Unauthorized Services

Laboratories are not permitted to obtain prior authorization or participate in authorization, appeals, or related administrative processes on behalf of the ordering physician. Only the ordering physician may be involved in authorization or appeal activities. Use of a laboratory representative or third party to obtain authorization on behalf of the ordering physician is a violation and may result in severe action, including termination from the BCBSRI provider network. If a laboratory provides a laboratory service that has not been authorized, the service will be denied and the financial liability will rest with the participating laboratory; the laboratory may not bill the member for the denied service.

Only the ordering physician may be involved in prior authorization, appeal, or other administrative processes.
If a laboratory or third party supports authorization improperly, BCBSRI may take severe action up to network termination.
Unauthorized laboratory services will be denied and billed as the laboratory's financial responsibility; providers may not bill members for denied services except as allowed with documented member consent.

Ordering and Authorization Guidance

Note

Ordering requirement — labs must not obtain prior authorization for clinicians

Only the ordering physician may initiate or participate in authorization and appeal processes; laboratories must not obtain prior authorization on behalf of the ordering clinician or use representatives to facilitate authorization.

Violation of this requirement may result in severe action, including termination from the BCBSRI provider network.

Note

Ordering requirement — verify benefits and eligibility before ordering

Verify member-specific benefits and eligibility prior to ordering by contacting the provider call center and reviewing the member's subscriber or employer agreement; this policy does not guarantee payment.

Benefits and eligibility documentation supersede this medical policy.

Not Covered / Not Medically Necessary Services

The policy lists specific procedure codes that are considered not covered for Medicare Advantage Plans and not medically necessary for Commercial Products when billed for cerebrospinal fluid, blood, or urinary biomarker testing for Alzheimer disease. Named codes include 0361U, 0412U, 0443U, 0445U, and related unlisted procedure codes that may be used to report urine, CSF, or immunoassay testing (for example, 81099, 86849, 83520). Providers must use the appropriate CPT/HCPCS code(s) and verify coverage prior to performing or billing these tests.

The policy notes that some related tests and services are not separately itemized in every section; where a service is determined to be not medically necessary or is a non-covered benefit, it may be excluded from payment. Providers should not assume payment for services described as non-covered or not medically necessary and must confirm member benefits before ordering or billing.

Definitions and Clinical Terms

Mild cognitive impairment (MCI)

DefinitionMild cognitive impairment (MCI) is significant cognitive change with impairment in one or more cognitive domains while functional independence is preserved

Clinical contextMCI may be a predementia phase of Alzheimer disease; diagnosis is made when dementia criteria are not met but cognitive decline is present

Ancillary evaluationPatients with MCI or suspected AD may undergo neuroimaging, laboratory tests, and neuropsychological assessment to rule out other causes

CSF biomarkers (Aβ42, total/phospho-tau)

What they areCSF biomarkers include Aβ42 and tau (total tau or phosphorylated tau) measured in cerebrospinal fluid; ratios such as tau/Aβ42 may improve diagnostic accuracy

Pathophysiologic relevanceLow CSF Aβ42 and elevated CSF tau reflect amyloid plaque deposition and neuronal degeneration typical of Alzheimer disease

Analytical considerationsVarious commercial kits exist and between-laboratory variability in CSF biomarker measurement is large; CLIA-certified lab testing required for LDTs

CSF and blood Alzheimer's disease biomarkers

Primary analytesPhosphorylated tau (p-tau; e.g., p-tau181, p-tau217) and amyloid-beta measures (Aβ42, Aβ42/40 ratio)

Specimen typesMeasured in cerebrospinal fluid and plasma/serum (blood-based assays such as plasma p-tau and Aβ42/40) for diagnostic support

Clinical roleUsed to support diagnosis and staging of Alzheimer disease and to discriminate AD from other neurodegenerative disorders in conjunction with clinical assessment

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