Proposed Alzheimer’s classification system relies solely on biomarkers
• A+/T-/N- is analogous to NIA-AA preclinical AD stage 1 and IWG asymptomatic at risk for AD (if A+ is established by amyloid PET).
• A+/T+/N- and A+/T+/N+ are analogous to NIA-AA preclinical AD stage 2/3 and IWG asymptomatic at risk for AD.
For MCI patients:
• A+/T-/N-, A+/T+/N-, and A+/T-/N+ are all analogous to the NIA-AA MCI core clinical criteria and IWG typical AD.
• A+/T+/N+ is analogous to NIA-AA MCI probably due to AD and IWG typical AD.
The A/T/N system offers the most useful details for patients who meet clinical criteria for probable AD dementia. Here, clinical criteria can be considered to help clarify the diagnostic picture:
• A-/T-/N-, analogous to NIA-AA dementia unlikely due to AD and is undefined by IWG.
• A+/T-/N-, analogous to NIA-AA intermediate likelihood of probable AD dementia, based on clinical criteria, and IWG typical AD (if A+ is established by amyloid PET).
• A+/T+/N-, analogous to NIA-AA high likelihood of probable AD dementia, based on clinical criteria, and IWG typical AD.
• A+/T-/N+, analogous to NIA-AA high likelihood of probable AD dementia, based on clinical criteria, and IWG typical AD (if A+ is established by amyloid PET).
• A+/T+/N+, analogous to NIA-AA high likelihood of AD pathophysiology and IWG typical AD.
• A-/T+/N+, analogous to NIA-AA probable AD dementia, based on clinical criteria and is undefined by IWG.
• A-/T-/N+, analogous to NIA-AA intermediate likelihood of probable AD dementia, based on clinical criteria, and is undefined by IWG.
• A-/T+/N+, analogous to NIA-AA intermediate likelihood of probable AD dementia, based on clinical criteria, and is undefined by IWG.
Would the A/T/N system benefit diagnostic accuracy?
The August paper sheds some additional light on how the system could hone diagnostic accuracy.
“For example, an A-/T-/N+ profile would be expected with pathologies such as ischemic cerebrovascular disease or hippocampal sclerosis, whereas an A-/T+/N+ profile would be expected with primary age-related tauopathy. An A+/T-/N+ profile might indicate an individual in the earliest stage of preclinical AD (accounting for the A+/T- status), who also has a non-AD pathology such as hippocampal sclerosis (accounting for the N+ status).”
Other typical profiles will certainly emerge as the A/T/N system is applied in large cohorts, the paper noted.
While the system is now aimed at building stronger research cohorts, it may eventually be adopted – and adapted – by clinicians.
“Right now, the reality is that most clinical practices don’t have access to getting these biomarkers,” Dr. Jack said. “Having said that, we also know that clinicians will vote with their feet. If they think this is useful they’ll end up adopting it, at least in the highly specialized centers that have access to these tests. The ultimate outcome someday will be a clinical practice guideline where people don’t get the label of AD unless they really have positive biomarkers.”
Dr. Jack has been a consultant for Eli Lilly.
On Twitter @alz_gal
