Confirm biomarker method and coverage

Confirm the specific biomarker method (CSF, plasma, or urine) and verify member coverage/payer benefits before ordering testing; FDA‑cleared PLA codes for relevant assays (e.g., 0445U, 0459U) are listed in the coding section and may affect coverage.

• Confirm whether the intended test is FDA‑cleared, CLIA‑certified LDT, or NY‑permitted LDT as applicable.
• Verify member benefits and any prior authorization requirements for the specific assay/PLA code.

Prior authorization for FDA‑cleared assays

When using FDA‑cleared CSF or plasma assays, be prepared to provide clinical indication and numeric test results for prior authorization; the policy identifies FDA‑cleared assays in Table 2 and notes related device/code listings.

• Document the specific FDA clearance or De Novo/510(k) number if available.
• Include numeric result relative to manufacturer cutoff in prior authorization submission.

Prior authorization for biomarker testing

Prior authorization may be required when biomarker testing is used to evaluate individuals with MCI or dementia; supporting documentation should show the test’s intended role, population, and evidence of analytic/clinical validity.

• Provide clinical diagnosis (MCI or mild dementia due to AD) and staging consistent with NIA‑AA criteria.
• Supply assay identification and how results will impact treatment decisions.

Prior authorization may be required (evidence‑limited contexts)

Although not all sections specify PA rules, the document emphasizes limited evidence of clinical utility outside therapy selection—payers may therefore require justification or prior authorization for CSF/plasma/urine biomarker tests.

• Expect requests to justify how testing will change management or meet therapy‑selection criteria.
• Be ready to reference clinical validity data if available.

Prior authorization not stated in some sections

Some excerpts do not state prior authorization requirements; confirm payer‑specific PA rules locally before ordering.

• Check local Medicare carrier policies because no national Medicare determination exists.
• Coordinate with the payer's implementation team for PA processes.

Testing for therapy selection

If testing is intended to select patients for amyloid‑targeted therapy, use validated CSF biomarkers or PET to confirm amyloid pathology per trial/label criteria; document how results will inform therapy selection.

• Ensure the individual meets population criteria (MCI or mild dementia due to AD) and clinical staging consistent with trial entry criteria.
• If PET is unavailable, use CSF Aβ42/40 or t‑tau/Aβ42 per policy guidance.

Confirmation of amyloid pathology required

Prior authorization for initiation of anti‑amyloid therapy should require confirmation of amyloid beta pathology (positive amyloid PET or CSF biomarkers such as ttau/Aβ42 or Aβ42/40) prior to approving treatment.

• Attach PET or CSF documentation demonstrating amyloid positivity when requesting authorization for lecanemab or donanemab.
• Reference RCT eligibility criteria (Clarity AD, TRAILBLAZER) when applicable.

Specialist evaluation and confirmatory testing expected

Specialist (dementia specialist) evaluation is expected for use of blood‑based biomarkers; positive BBM results should be confirmed with CSF or amyloid PET given emerging status and reimbursement limitations.

• Use BBMs as prescreeners only in specialized settings and obtain confirmatory testing per guideline recommendations.
• Document specialist assessment and rationale for BBM use.

Prior authorization determined locally

In the absence of a national Medicare coverage determination, local Medicare carriers or the payer determine prior authorization requirements—verify local carrier rules for Medicare members.

• Check local Medicare carrier guidance for PA and coverage decisions prior to ordering.
• Be aware that local carrier discretion may lead to denials if requirements are not met.

Prior authorization for specified biomarker assays

Verify and obtain any required prior authorization for the specific PLA/CPT/algorithmic assay codes listed (e.g., 0358U, 0412U, 0443U, 0445U, 0459U, 0479U, 0503U, 0568U) when submitting claims or PA requests.

• Include the exact PLA/CPT code and test name in the authorization/claim submission.
• Confirm whether investigational plasma tests listed are eligible for coverage.

Provider actions overview

Providers must follow policy requirements for ordering and documentation of biomarker testing; see individual policy statements for investigational designations and PA expectations.

• Order testing only for appropriate indications (MCI or mild dementia being evaluated for AD) per policy.
• Avoid testing for inappropriate indications listed in the policy.

Testing to establish eligibility for amyloid‑targeted therapies

Demonstration of amyloid positivity (amyloid PET or CSF biomarker evidence) was required in pivotal trials of amyloid‑targeting therapies and may be needed to establish eligibility for treatment.

• When seeking therapy authorization, include PET or CSF documentation consistent with trial eligibility (e.g., ttau/Aβ42 or PET visual read).
• Note that donanemab trials used PET-only eligibility; lecanemab allowed PET or CSF.

Clinical diagnosis and differential diagnosis expectations

Clinical diagnosis and staging consistent with NIA‑AA criteria and consideration of differential diagnoses (eg, vascular dementia, DLB, FTD) should precede biomarker testing and be documented.

• Document cognitive testing and staging (MMSE, CDR, RBANS/WMS measures) used to establish MCI or mild dementia.
• Record differential diagnostic considerations and why biomarkers are indicated.

Comparator expectations (amyloid PET)

Amyloid PET is a recognized comparator with very high sensitivity and specificity and has been used in trials to select individuals for therapy; when available, PET is preferred or used as a reference for test concordance.

• If PET is not available, provide rationale and demonstrate CSF equivalency if using CSF tests to support therapy decisions.
• Explain concordance between the chosen biomarker and PET where relevant.

Continuation monitoring — serial biomarker testing not supported

There is insufficient evidence to support serial biomarker testing (CSF or plasma) to guide continuation of amyloid‑targeting therapy; do not base continuation solely on serial biomarker changes.

• Use clinical and imaging assessments per guidelines to evaluate continuation decisions.
• Avoid ordering serial biomarker tests solely for monitoring therapy response absent evidence.

BBM triage then confirm (blood prescreening then confirm with PET/CSF)

Use blood‑based markers only as prescreeners or triage tests; positive BBM results should be confirmed with amyloid PET or CSF testing before using results to make treatment decisions.

• Document BBM result, rationale for triage use, and plan for confirmatory CSF or PET testing.
• Do not substitute BBM alone for confirmatory testing when selecting anti‑amyloid therapy.

CSF confirmation before anti‑amyloid therapy (clinical input support)

Clinical input supports selecting individuals for anti‑amyloid therapy using CSF biomarker evidence of amyloid and tau (ratios and FDA‑cleared CSF tests); document assay and results when used for therapy selection.

• Prefer CSF Aβ42/40 ratio or t‑tau/Aβ42 and FDA‑cleared CSF assays when establishing eligibility for lecanemab.
• Attach clinical input or specialty justification when CSF is used in lieu of PET.

Provider actions — documentation confirming amyloid pathology for therapies

When ordering biomarker testing to support therapy initiation, include documentation that confirms amyloid pathology (positive amyloid PET or CSF biomarkers) consistent with RCT protocols and drug labels.

• Provide PET visual read or CSF numeric ratio values tied to manufacturer cutoffs in the authorization packet.
• State how the result meets trial or label requirements for therapy initiation.

Test identification and numeric results documentation

Document the specific test performed and the numeric result relative to the manufacturer cutoff (e.g., Lumipulse G amyloid ratio, Elecsys p‑tau181), including patient age group as indicated in the test's intended use.

• Record the assay name, platform, and numeric value and indicate whether result is positive/negative/indeterminate per cutoff.
• Include laboratory report and method (PLA/CPT/CLIA) with claims or PA requests.

Laboratory regulatory documentation requirements (LDT/CLIA/NY State)

If the test is a laboratory‑developed test (LDT), document CLIA certification and, for New York specimens or NY labs, the New York State Department of Health permit and proficiency testing participation.

• Include CLIA certificate number and NY DOH permit ID when submitting claims or PA.
• Provide evidence of proficiency testing participation if requested.

Clinical validity study population and reference standard documentation

Be prepared to document that the assay’s clinical validity was established in an appropriate study population and compared with a credible reference standard (PET or CSF), especially when used for treatment decisions.

• Provide citations or study summaries showing study population, reference standard, and reported sensitivity/specificity where available.
• Explain generalizability of study population to the patient being evaluated.

Assay and reference standard documentation (assay platforms e.g., Lumipulse)

Document the assay platform and reference standard used in validation studies (examples include Fujirebio Lumipulse G1200 and predefined PET/CSF reference standards) when relying on assay performance for clinical decisions.

• Attach assay platform details and validation study references in PA submissions.
• Indicate whether the lab used FDA‑cleared method or validated LDT.

Data collected in FDA clinical cohort (clinical assessments listed)

When seeking authorization related to therapies, include clinical assessments and study‑style data collected in FDA cohorts (eg, QDRS, MMSE, CDR, MRI, amyloid PET) to demonstrate alignment with trial entry criteria.

• Provide cognitive testing scores (MMSE, CDR) and relevant imaging reports.
• Include medication history and functional assessments when available.

Clinical documentation expectations (battery of cognitive tests)

Perform and document a battery of cognitive tests and staging (eg, MMSE, CDR, RBANS/WMS measures) when evaluating individuals with suspected MCI or mild dementia prior to biomarker testing.

• Include objective cognitive testing results and staging consistent with NIA‑AA criteria.
• Document functional impairment and history corroboration from informant when applicable.

Confirmatory documentation for treatment initiation

Before initiating anti‑amyloid therapy, include confirmatory documentation that demonstrates amyloid pathology by CSF biomarker assessment or amyloid PET, as required by RCT protocols and drug labels.

• Provide CSF ratio values (t‑tau/Aβ42 or Aβ42/40) or PET positive read in authorization packet.
• Cite trial protocols (Clarity AD) or label statements if requested by payer.

Document clinical evaluation and biomarker evidence within multi‑tier diagnostic evaluation

Document where biomarker testing fits within a multi‑tiered diagnostic evaluation (Tier 1 labs, structural imaging) and include clinical criteria plus biomarker results for biomarker‑supported probable AD.

• Attach Tier 1 lab results and structural imaging (MRI) reports alongside biomarker results.
• State how biomarker results increase diagnostic certainty for probable AD.

Essential Health Benefits implications for plans

Plans subject to Essential Health Benefits may have state‑specific implications; for insured small group and individual plans, be aware that state EHB definitions can affect documentation and coverage.

• Check state EHB definitions for required coverage or any exclusions that may apply.
• Document plan type and EHB applicability on submission if relevant.

Assay identification on claim (CPT/PLA/CLIA test name)

When submitting claims, identify the exact assay or PLA/CPT/CLIA test name or code on the claim (policy lists multiple specific test codes and named assays).

• Use the listed PLA/CPT code that corresponds to the performed assay (e.g., 0358U, 0445U, 0459U, 0503U, 0568U).
• Ensure lab report matches billed code to reduce claim denials.

Provider action — adjunctive testing used as adjunct to clinical diagnosis (policy stance)

Biomarker testing should be used as an adjunct to a comprehensive clinical evaluation; document that testing is adjunctive and will be interpreted with other clinical information rather than as a stand‑alone diagnostic test.

• Note in record that assay is not intended as a screening or stand‑alone diagnostic test where manufacturer guidance indicates this.
• Provide clinical context and differential diagnosis with biomarker interpretation.

Result interpretation and follow‑up expectations

Provide interpretation of results in context and plan for follow‑up; results inconsistent with established cutoffs (positive/negative/indeterminate) may require confirmatory testing or further evaluation.

• If result is indeterminate per assay cutoffs, plan confirmatory CSF or PET testing and document rationale.
• Explain how result will change patient management or lead to further diagnostic steps.

Study reporting expectations (sensitivity/specificity/PV/PPA/NPA)

If relying on study data or reporting test performance, be prepared to provide sensitivity, specificity, predictive values, or PPA/NPA as reported in validation studies; lack of credible methodologic evidence may lead to noncoverage.

• Attach study performance metrics and reference standards used in validation.
• Explain applicability of study population to the treated patient.

Potential basis for denial — investigational adjunctive testing

Claims for CSF, plasma, or urine biomarker tests used as adjuncts to clinical diagnosis may be denied because the policy designates such adjunctive uses as investigational and not medically necessary outside specified therapy‑selection contexts.

• Testing ordered for inappropriate indications (listed in policy) risks denial.
• If ordering, document how testing meets an allowed indication and will affect management.

Provider‑level authorization/denial rules not stated in some excerpts — be prepared to document

If test results fall outside established cutoffs or are indeterminate, expect requests for confirmatory testing and interpretive follow‑up; such inconsistencies can affect coverage and clinical decisions.

• Provide numeric cutoff comparison and laboratory interpretation notes with the claim or PA.
• Plan and document next diagnostic steps for indeterminate or conflicting results.

Clinical risk driving coverage decisions (misclassification, ARIA implications)

Misclassification (false positives or false negatives) can lead to inappropriate therapy selection or exposure to ARIA; document test performance and rationale to mitigate clinical risk.

• Describe risk‑benefit assessment when using biomarker results to recommend anti‑amyloid therapy.
• Provide evidence supporting assay accuracy for the intended clinical use.

Plasma biomarkers substitution risk

Do not substitute plasma biomarkers alone for CSF or amyloid PET to select patients for anti‑amyloid therapy in routine clinical practice unless prospective non‑inferiority data in clinical settings are provided; lack of such data places claims at risk for denial.

• If using plasma tests, document why confirmatory CSF or PET is not feasible and provide supporting validation evidence.
• Explicitly note research‑condition limitations if relying on plasma equivalency data.

Lumipulse recall (Class 2) — impact on plasma ratio testing

Be aware the Lumipulse plasma ptau217/Aβ42 ratio test is subject to an active FDA Class 2 recall for falsely elevated ratio results; positive results from this assay may prompt additional review or denial.

• If Lumipulse plasma ratio was used, include lab recall status and any lab corrective actions in documentation.
• Consider confirmatory CSF or PET testing given the recall status.

Inappropriate indications may be denied

Testing for indications listed as inappropriate (eg, cognitively unimpaired without risk factors, APOE ε4 carriers without impairment, using LP instead of genotyping for ADAD) may be denied; avoid ordering for these scenarios.

• Review the policy's Inappropriate Indications list before ordering tests.
• Document presence of risk factors or clinical rationale if ordering in borderline cases.

Medicare local carrier discretion (may affect denials/approvals)

Local Medicare carrier discretion may lead to varying coverage outcomes; for Medicare patients, verify local carrier rules to avoid unexpected denials.

• Contact the local Medicare contractor for coverage guidance prior to testing when possible.
• Include local carrier correspondence in the PA or claim if available.

Investigational plasma tests — claims may be denied

Plasma‑based algorithmic and multi‑analyte tests (eg, PrecivityAD, PrecivityAD2, LucentAD) are designated investigational in this policy; claims for these plasma tests may be denied.

• Do not rely on investigational plasma tests alone to justify therapy initiation or continuation.
• If such testing was performed, document clinical rationale and be prepared for denial.