Is there a generalized cutoff age for amyloid treatment?

Age Considerations for Amyloid Treatment

There is no absolute age cutoff for amyloid treatment, but treatment decisions should be guided by the type of amyloidosis, disease stage, and patient factors rather than chronological age alone.

Types of Amyloidosis and Age Considerations

Transthyretin (ATTR) Amyloidosis

• The American Heart Association/American College of Cardiology guidelines recommend tafamidis for patients with wild-type or variant transthyretin cardiac amyloidosis with NYHA class I to III heart failure symptoms, without specifying an age limit 1
• Blood biomarker tests for amyloid pathology are recommended for:
  • Triaging: Patients aged ≥55 years
  • Confirmation: Patients aged ≥65 years 1
• Younger individuals (<55 years) may still be tested if clinical suspicion for amyloid pathology is high due to:
  • Clinical syndrome consistent with symptomatic Alzheimer's disease
  • Family history of early-onset dementia in first-degree relatives
  • Down syndrome 1

Light Chain (AL) Amyloidosis

• Treatment decisions should be based on organ involvement and disease stage rather than age alone 1
• Age is a significant factor affecting survival in AL amyloidosis, with patients <65 years having better outcomes than those ≥65 years 1
• Treatment intensity should be adjusted based on frailty assessment, which includes age, number and type of organs involved, and pre-existing comorbidities 1

Diagnostic Approach by Age

For Cardiac Amyloidosis

1. Clinical suspicion should be high when left ventricular wall thickness ≥14 mm occurs with fatigue, dyspnea, or edema, especially with discordance between wall thickness and ECG voltage 1
2. Screening should include serum and urine monoclonal light chains with immunofixation electrophoresis and serum free light chains 1
3. If no evidence of monoclonal light chains, bone scintigraphy should be performed to confirm ATTR cardiac amyloidosis 1
4. Genetic testing with TTR gene sequencing is recommended to differentiate hereditary variant from wild-type ATTR cardiac amyloidosis 1

For Alzheimer's Disease-Related Amyloid

• Amyloid PET imaging is considered appropriate for 1:
  • Patients with atypically young-onset dementia (typically 50-65 years)
  • Patients with possible Alzheimer's disease (atypical clinical course or mixed presentation)
• Amyloid PET is not appropriate for 1:
  • Patients meeting core clinical criteria for probable Alzheimer's disease with typical age of onset
  • Determining dementia severity
  • Testing based solely on family history or APOE genotype

Treatment Recommendations Based on Amyloid Type

ATTR Amyloidosis

• Tafamidis is indicated for patients with wild-type or variant ATTR cardiac amyloidosis with NYHA class I to III heart failure symptoms 1, 2
• TTR silencer therapy for patients with neuropathy 1
• Anticoagulation for patients with atrial fibrillation 1
• Liver transplantation can be curative for ATTR amyloidosis as it removes the source of TTR protein production 2

AL Amyloidosis

• Treatment should be risk-adapted based on patient factors including age, organ involvement, and disease stage 1
• First-line treatments include bortezomib-based regimens (CyBorD) or daratumumab 2
• High-dose melphalan followed by autologous stem cell transplantation may be considered for eligible patients 2
• Heart transplantation may be considered in select patients with advanced/stage D heart failure 2

Monitoring Recommendations

• Monthly monitoring: CBC, basic biochemistry, NT-proBNP, troponin, and serum-free light chain quantification 2
• Every 6 months: Echocardiography with strain measurements and Holter ECG 2
• A multidisciplinary approach involving hematologists, cardiologists, nephrologists, neurologists, and palliative care specialists is essential 2

Key Considerations Beyond Age

1. Disease Stage: More important than age in determining prognosis and treatment approach
2. Organ Involvement: Cardiac involvement is the most important prognostic factor in AL amyloidosis
3. Functional Status: Performance status and comorbidities are better predictors than chronological age alone
4. Biomarker Profile: NT-proBNP and eGFR can stratify patients into prognostic categories regardless of age 3

Rather than using a strict age cutoff, treatment decisions for amyloidosis should be guided by comprehensive assessment of disease type, stage, organ involvement, and patient factors to optimize outcomes and quality of life.