Does one check for beta amyloid (Beta-Amyloid) in a person with cognitive decline?

From the Guidelines

Checking for beta-amyloid is a crucial part of the evaluation for a person with cognitive decline, particularly when Alzheimer's disease is suspected, and should be considered in cases where diagnostic uncertainty remains after a comprehensive workup. This is typically done through specialized tests like PET scans using amyloid-binding tracers or by measuring beta-amyloid levels in cerebrospinal fluid obtained through a lumbar puncture 1. However, these tests are not routinely performed in all cases of cognitive decline. They are usually reserved for situations where the diagnosis is unclear, for relatively young patients with cognitive symptoms, for research purposes, or when specific treatments targeting amyloid are being considered.

• Beta-amyloid plaques are a hallmark pathological feature of Alzheimer's disease, but their presence doesn't always correlate perfectly with cognitive symptoms, as some people with amyloid plaques may not show cognitive impairment 1.
• The decision to test for beta-amyloid should be made by a neurologist or other specialist familiar with cognitive disorders based on the individual clinical situation, taking into account the potential benefits and risks of the test, including the risk of bleeding complications associated with lumbar puncture in patients taking anticoagulant medications 1.
• Amyloid PET results directly impact medical decision making regarding the use of disease-modifying therapies and is a sufficient test for establishing the presence of amyloid-beta pathology which must be confirmed prior to initiating treatment 1.
• The interpretation of results in the clinical context may be difficult, because a sizeable percentage of cognitively normal older adults harbor these pathologic markers of AD, with the percentage increasing with age over ≈ 60 1.
• Blood biomarker tests for amyloid status have unique advantages over amyloid PET and CSF tests, including being safe and acceptable to most patients, and can be scaled up more easily than other AD biomarker modalities 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE Amyvid is indicated for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's Disease (AD) and other causes of cognitive decline

1 INDICATIONS AND USAGE Neuraceq is indicated for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s Disease (AD) and other causes of cognitive decline

Yes, one checks for beta amyloid in a person with cognitive decline using PET imaging with agents such as florbetapir (IV) 2 or florbetaben (IV) 3, as an adjunct to other diagnostic evaluations.

• A positive scan indicates moderate to frequent amyloid neuritic plaques, which may be present in patients with AD, but also in patients with other neurologic conditions or older people with normal cognition.
• A negative scan indicates sparse to no neuritic plaques and reduces the likelihood that a patient's cognitive impairment is due to AD.

From the Research

Checking for Beta Amyloid in Cognitive Decline

• Beta amyloid PET scans are a minimally invasive biomarker that may inform Alzheimer's disease (AD) diagnosis 4
• The overall performance of Aβ PET in diagnosing AD is favorable, but the differentiation between mild cognitive impairment (MCI) and AD patients should consider that some MCI may be at risk of conversion to AD and may be misdiagnosed 5
• Aβ PET had high sensitivity (0.91) and specificity (0.81) for differentiating AD from normal controls but very poor specificity (0.49) for determining AD from MCI 5

Diagnostic Approaches

• A multimodal diagnostic approach and machine learning analysis may be effective in improving diagnostic accuracy 5
• Nuclear neuroimaging in AD has made great progress in the past two decades and has extended beyond the traditional role of brain perfusion and glucose metabolism evaluation 6
• SPECT and PET have proposed to serve as biomarkers in recently revised diagnostic clinical criteria for the early diagnosis of AD and the prediction of progression to AD in MCI subjects 6

Implications for Practice and Research

• Findings suggest a need for carefully designed and tested tools for clinicians to discuss risks and benefits of scans and their results, and resources to support patients and care partners in subsequent planning 4
• Learning of scan results provides a point-of-contact that should be leveraged to facilitate shared decision-making and person-centered longitudinal AD care 4
• Future Alzheimer's clinical trials should disregard amyloid-PET imaging and focus instead on assessment of regional brain function by FDG-PET and MRI monitoring of ARIAs and brain volume loss in all trial patients 7

Association with Cognitive Decline

• Higher levels of Aβ and tau were both associated with greater memory decline, but not with change in executive function 8
• A significant interaction between tau and Aβ was observed in both ROI and map-level analyses, such that rapid prospective memory decline was observed in participants who had high levels of both pathologies 8