Can you have Alzheimer's (Alzheimer's disease) dementia with a normal amyloid positron emission tomography (PET) scan?

Alzheimer's Disease and Amyloid PET Imaging: Diagnostic Implications

A negative amyloid PET scan makes a diagnosis of Alzheimer's disease highly unlikely, as the absence of amyloid plaques strongly argues against AD pathology, though rare exceptions may exist in certain clinical scenarios. 1

Understanding Amyloid PET in AD Diagnosis

Amyloid PET imaging detects one of the defining pathological hallmarks of Alzheimer's disease - amyloid-β deposition in the brain. The relationship between amyloid PET findings and AD diagnosis follows these principles:

Negative Amyloid PET Scans

• A negative amyloid PET scan indicates low probability of AD and suggests consideration of non-AD neurodegenerative conditions 1
• The high sensitivity of amyloid PET for AD pathology means that a negative scan effectively rules out AD in most clinical scenarios 1
• However, a negative scan does not exclude the possibility of other neurodegenerative conditions that could cause cognitive impairment 1

Positive Amyloid PET Scans

• While a positive amyloid PET supports AD pathology, it is not sufficient alone for diagnosis
• Amyloid positivity can be present in:
  • Cognitively normal older individuals (20-30% of those over 75) 2
  • Patients with non-AD dementias as a comorbid finding 1
  • Individuals with other neurological conditions alongside AD pathology

Clinical Implications and Diagnostic Algorithm

1. For patients with cognitive impairment and suspected AD:

   • If amyloid PET is negative → AD diagnosis is highly unlikely
   • If amyloid PET is positive → Consider clinical context:
     • Typical AD presentation + positive amyloid PET = high probability of AD
     • Atypical presentation + positive amyloid PET = possible AD or mixed pathology

2. Age and genetic considerations:

   • Younger patients (<65 years) with negative amyloid PET → virtually excludes AD
   • Older patients (>75 years) with positive amyloid PET → higher chance of incidental amyloid positivity 2
   • ApoE4 carriers have higher rates of amyloid positivity regardless of cognitive status 2

3. Diagnostic confidence adjustment:

   • Positive predictive value is highest in younger patients without ApoE4 who have high pre-test probability of AD
   • Negative predictive value is extremely high except in very elderly patients with strong clinical AD features 2

Important Caveats and Pitfalls

• Amyloid PET is not a test for dementia but rather indicates underlying pathology that must be interpreted in clinical context 1
• Appropriate use criteria limit amyloid PET to specific scenarios:
  • Persistent/progressive unexplained MCI
  • Possible AD with atypical presentation or mixed etiology
  • Early-onset dementia (<65 years) 1
• Inappropriate use includes:
  • Typical probable AD with typical age of onset
  • Determining dementia severity
  • Asymptomatic individuals
  • Unconfirmed cognitive complaints 1

Interpreting Results in Clinical Practice

The Amyloid Imaging Task Force, Society of Nuclear Medicine and Molecular Imaging, and Alzheimer's Association emphasize that amyloid PET should be used only by dementia experts who can properly integrate imaging results with comprehensive clinical evaluation 1.

For optimal interpretation:

• Consider patient age (higher incidental amyloid with advancing age)
• Evaluate clinical syndrome (typical vs. atypical presentation)
• Assess for other contributing pathologies
• Recognize that amyloid deposition is necessary but not sufficient for AD diagnosis

Remember that while a negative amyloid PET scan strongly argues against AD pathology as the cause of cognitive impairment, rare exceptions may exist, particularly in very early disease or unusual presentations.