How to manage elevated serum amyloid levels in patients with dementia?

Management of Elevated Serum Amyloid Levels in Patients with Dementia

Patients with elevated serum amyloid levels in dementia should undergo regular brain MRI monitoring for ARIA (Amyloid-Related Imaging Abnormalities) if receiving anti-amyloid monoclonal antibody therapy, with specific MRI timing before the 5th, 7th, and 14th infusions, and temporary or permanent cessation of treatment if ARIA develops. 1

Diagnostic Approach for Serum Amyloid Elevation

When elevated serum amyloid is detected in patients with dementia, follow this algorithmic approach:

Initial Assessment

• Confirm the diagnosis of dementia using validated cognitive assessment tools
• Determine if the patient has mild, moderate, or severe dementia
• Evaluate if amyloid pathology is the likely underlying cause through:
  • Clinical presentation assessment
  • Comprehensive laboratory testing to rule out reversible causes
  • Brain imaging with MRI (or CT if MRI is contraindicated) 2

Biomarker Confirmation

• Blood biomarker (BBM) tests for amyloid can be used as:

  • A triaging test (sensitivity ≥90%, specificity ≥75-85%)
  • A confirmatory test in appropriate populations 1

• Consider the pre-test probability based on age:

  • For patients ≥65 years: BBM tests can be used for confirmation
  • For patients 55-64 years: BBM tests recommended for triaging only
  • For patients <55 years: BBM tests only if high clinical suspicion 1

• If blood biomarker results are inconclusive or if treatment decisions depend on accurate amyloid status, consider:

  • CSF analysis for Aβ, tau, and phospho-tau 1
  • Amyloid PET imaging in select cases 1

Management of Patients with Confirmed Amyloid Pathology

For Patients Eligible for Anti-Amyloid Therapy

1. Pre-treatment Assessment:

   • Obtain baseline MRI within 12 months before initiating therapy 1
   • Screen for contraindications to anti-amyloid therapy

2. Monitoring During Treatment:

   • Schedule routine MRI scans:
     • Before the 5th infusion
     • Before the 7th infusion
     • Before the 14th infusion 1
   • Additional MRI if clinical symptoms of ARIA develop
   • Required MRI sequences: DWI, T2 FLAIR, and T2* GRE or SWI 1

3. Management of ARIA:

   • If ARIA-E (edema) or ARIA-H (hemorrhage) detected:
     • Grade as mild, moderate, or severe
     • Modify treatment based on severity (temporary or permanent cessation)
     • Consider corticosteroids or antiepileptic treatment if symptomatic 1

For Patients Not Eligible for Anti-Amyloid Therapy

• Consider standard dementia treatments:
  • Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) 3
  • Memantine for moderate to severe dementia 2
  • Non-pharmacological interventions (cognitive training, physical activity, Mediterranean diet) 2

Special Considerations and Pitfalls

Age-Related Considerations

• Younger patients (<65 years):

  • Higher specificity needed for amyloid testing
  • Consider genetic testing for familial forms of AD
  • More extensive workup required 2

• Older patients (≥65 years):

  • Higher pre-test probability of amyloid pathology (prevalence ~68-90% in AD) 4
  • Blood biomarker tests may be sufficient for confirmation 1

APOE ε4 Status Impact

• APOE ε4 carriers have higher prevalence of amyloid positivity:
  • In AD dementia: 90-97% depending on age 4
  • In non-AD dementias: significantly higher than non-carriers 4
• Consider APOE testing to help interpret amyloid results

Common Pitfalls to Avoid

1. Misinterpreting amyloid positivity: Amyloid plaques can occur in non-AD dementias (29-83% in Lewy body dementia, 5-43% in frontotemporal dementia) 4

2. Overlooking ARIA: Failing to monitor for ARIA in patients on anti-amyloid therapy can lead to serious complications. ARIA-E occurs in up to 35-36% of patients on aducanumab, 26.7% on donanemab, and 12.6% on lecanemab 1

3. Inadequate follow-up: Regular monitoring is essential, especially when anti-amyloid therapy is initiated

4. Missing treatable causes: Always complete first-tier laboratory testing before concluding a primary neurodegenerative process 2

By following this structured approach to managing elevated serum amyloid levels in dementia patients, clinicians can provide appropriate care while minimizing risks associated with both the disease and its treatments.